Aprepitant for the Relief of Nausea in Patients With Chronic Nausea and Vomiting of Presumed Gastric Origin Trial (APRON)

Aprepitant for the Relief of Nausea in Patients With Chronic Nausea and Vomiting of Presumed Gastric Origin: A Multicenter, Randomized, Double-Masked, Placebo-Controlled Trial

The principal objective of this multicenter, randomized, placebo-controlled trial is to evaluate whether 4 weeks of treatment with aprepitant will improve nausea as compared with placebo in patients with symptoms of chronic nausea and vomiting of presumed gastric origin.

Study Overview

• Status: Completed
• Conditions: Gastroparesis
• Intervention / Treatment: Drug: Aprepitant; Drug: Placebo

Detailed Description

APRON is a multicenter, randomized, double-masked, placebo controlled trial of 4 weeks of treatment with aprepitant or placebo for patients with symptoms of gastroparesis and related disorders. Screening for eligibility and collection of baseline data will span up to 4 weeks after obtaining informed consent and registration. Eligible patients will consist of patients with symptoms of gastroparesis and will be randomized to either aprepitant (125 mg per day) or placebo for 4 weeks.

The symptoms will be measured with the Gastroparesis Cardinal Symptom Index Daily Diary (GCSIDD) for one week at baseline and for four weeks after randomization. In addition, the nausea symptom will be measured daily on a 0 to 100 mm visual analog scale (VAS) for one week at baseline and daily for four weeks after randomization. There will be a 2 week washout period at the end of the treatment to ensure patient safety following the end of treatment.

• Study Type: Interventional
• Enrollment (Actual): 126
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center
    • Stanford, California, United States, 94305-5187
      • Stanford University
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins Bayview Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Medical Center
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
  • Texas
    • El Paso, Texas, United States, 79905
      • Texas Tech University Health Sciences Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18 years or older at registration
• Gastric emptying scintigraphy within 2 years of registration
• Normal upper endoscopy or upper GI series within 2 years of registration
• Symptoms of chronic nausea or vomiting compatible with gastroparesis or other functional gastric disorder for at least 6 months (does not have to be contiguous) prior to registration with Gastroparesis Cardinal Symptom Index (GCSI) score of greater than or equal to 21
• Significant nausea defined with a visual analog scale (VAS) score of greater than or equal to 25 mm on a 0 to 100 mm scale

Exclusion Criteria:

• Another active disorder which could explain symptoms in the opinion of the investigator
• Use of narcotics more than 3 days per week
• Significant hepatic injury as defined by significant alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevations of greater than 2x the upper limit of normal (ULN) or a Child-Pugh score of 10 or greater
• Contraindications to aprepitant such as hypersensitivity or allergy
• Concurrent use of warfarin, pimozide, terfenadine, astemizole, or cisapride
• Pregnancy or nursing
• Any other condition, which in the opinion of the investigator would impede compliance or hinder the completion of the study
• Failure to give informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Aprepitant; Aprepitant 125 mg per day	Drug: Aprepitant; Aprepitant, 125 mg, 1 capsule, q.d. (everyday) with lunch for 4 weeks; Other Names: Emend
Placebo Comparator: Aprepitant-placebo; Placebo aprepitant 125mg per day	Drug: Placebo; Aprepitant-placebo, 125 mg, 1 capsule, q.d. (everyday) with lunch for 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Improvement in Nausea	The primary outcome measure is a binary (0,1) variable indicating improvement in nausea or not in the mean of available visual analog scale (VAS) scores over the 28 day treatment period compared to the mean of VAS scores during the 7 day baseline period. The criteria for improvement are either a 25 mm or more reduction in mean VAS or attaining a mean VAS during the treatment period of < 25 mm.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): Nausea (Hours)	Measure Description: Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): Nausea is the participant's assessment of the number of hours of nausea experienced in the past 24 hours. The range is 0 to 24 hours. The outcome measure, change from baseline in number of hours of nausea, has a possible range from -24 to +24, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): Vomiting (No. Episodes)	Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): Vomiting is the participant's assessment of the number of episodes of vomiting experienced in the past 24 hours. The outcome is the change from baseleine in number of times vomited, where negative numbers indicate improvement in vomiting frequency, and positive numbers indicate worsening in vomiting frequency.	4 weeks
Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): Retching (No. Episodes)	Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): Retching is the participant's assessment of the number of episodes of retching (heaving as if to vomit, but nothing comes up) experienced in the past 24 hours. The outcome is the change from baseline in the number of retching episodes, where negative numbers indicate improvement in retching frequency, and positive numbers indicate worsening in retching frequency.	4 weeks
Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): GCSI Total Score	The Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): GCSI total score is the average of 3 subscores: Nausea (average of two items: nausea and vomiting), Early Satiety (average of two items: not able to finish normal size meal and feeling excessively full after meals), and Bloating (feeling like you need to loosen your clothes). Each item is the participant's assessment of severity of the symptom during the past 24 hours, where 0=none, 1=mild, 2=moderate, 3=severe, and 4=very severe. The range of scores is 0 to 4, where higher scores are considered a worse outcome. The outcome measure, change from baseline in GCSI total score, has a possible range from -4 to +4, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): Nausea Severity	Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): Nausea severity is the participant's assessment of nausea (feeling sick to your stomach as if you were going to vomit or throw up) during the past 24 hours, where 0=none, 1=mild, 2=moderate, 3=severe, and 4=very severe. The range of scores is 0 to 4, where higher scores are considered a worse outcome. The outcome measure, change from baseline in GCSI score, has a possible range from -4 to +4, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): Vomiting Severity	Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): Vomiting Severity is the participant's assessment of vomiting during the past 24 hours, where 0=none, 1=mild, 2=moderate, 3=severe, and 4=very severe. The range of scores is 0 to 4, where higher scores are considered a worse outcome. The outcome measure, change from baseline in Vomiting Severity, has a possible range from -4 to +4, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): Upper Abdominal Pain Severity	Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): Upper Abdominal Pain Severity is the participant's assessment of upper abdominal pain (above the navel) during the past 24 hours, where 0=none, 1=mild, 2=moderate, 3=severe, and 4=very severe. The range of scores is 0 to 4, where higher scores are considered a worse outcome. The outcome measure, change from baseline in Upper Abdominal Pain Severity, has a possible range from -4 to +4, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): Excessive Fullness Severity	Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): Excessive Fullness Severity is the participant's assessment of excessive fullness (feeling excessively full after meals) during the past 24 hours, where 0=none, 1=mild, 2=moderate, 3=severe, and 4=very severe. The range of scores is 0 to 4, where higher scores are considered a worse outcome. The outcome measure, change from baseline in Excessive Fullness Severity, has a possible range from -4 to +4, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): Early Satiety Severity	Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): Early Satiety Severity is the participant's assessment of early satiety (not able to finish normal-size meal) during the past 24 hours, where 0=none, 1=mild, 2=moderate, 3=severe, and 4=very severe. The range of scores is 0 to 4, where higher scores are considered a worse outcome. The outcome measure, change from baseline in Early Satiety Severity, has a possible range from -4 to +4, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): Bloating Severity	Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): Bloating Severity is the participant's assessment of bloating (feeling like you need to loosen your clothes) during the past 24 hours, where 0=none, 1=mild, 2=moderate, 3=severe, and 4=very severe. The range of scores is 0 to 4, where higher scores are considered a worse outcome. The outcome measure, change from baseline in Bloating Severity, has a possible range from -4 to +4, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): Overall Symptom Severity	Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): Overall Symptom Severity is the participant's assessment of overall severity of gastroparesis symptoms during the past 24 hours, where 0=none, 1=mild, 2=moderate, 3=severe, and 4=very severe. The range of scores is 0 to 4, where higher scores are considered a worse outcome. The outcome, change from baseline in Overall Symptom Severity score, has a possible range from -4 to +4, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
Clinical Global Patient Impression Score (Patient-rated)	The Clinical Global Patient Impression Score quantifies the overall relief of the patient's symptom, by asking the participant to consider how they felt over the past week in regard to stomach symptoms and overall well-being, and rate relief of symptoms in comparison to how they felt before entering the study. Possible scores are: -3=very considerably worse, -2=considerably worse, -1=somewhat worse, 0=unchanged, 1=somewhat better, 2=considerably better, 3=completely better. The range of scores is -3 to 3, where higher scores are considered a better outcome. The outcome measure, change from baseline in Clinical Global Patient Impression Score, has a possible range of -6 to +6, with positive values indicating a better outcome (improvement) and negative values indicating a worse outcome.	4 weeks
Liver Enzymes and Proteins: Alanine Aminotransferase (ALT)	Change from baseline in serum alanine aminotransferase (ALT), U/L	4 weeks
Liver Enzymes and Proteins: Aspartate Aminotransferase (AST)	Change from baseline in aspartate aminotransferase (AST), U/L	4 weeks
Liver Enzymes and Proteins: Total Protein	Change from baseline in total protein (g/dL)	4 weeks
Hemoglobin A1c (HbA1c)	Change from baseline in hemoglobin A1c (HbA1c) (%)	4 weeks
Glucose	Change from baseline in glucose (mg/dL)	4 weeks
Liver Enzymes and Proteins: Albumin	Change from baseline in albumin (g/dL)	4 weeks
Hemoglobin	Change from baseline in hemoglobin (g/dL)	4 weeks
Hematocrit	Change from baseline in hematocrit	4 weeks
White Blood Cell Count (WBC)	Change from baseline in white blood cell count (WBC)	4 weeks
Red Blood Cell Count (RBC)	Change from baseline in red blood cell count (RBC)	4 weeks
Platelet Count	Change from baseline in platelet count	4 weeks
Carbon Dioxide	Change from baseline in carbon dioxide (mEg/L)	4 weeks
Chloride	Change from baseline in chloride (mEq/L)	4 weeks
Sodium	Change from baseline in sodium (mEq/L)	4 weeks
Potassium	Change from baseline in potassium (mEq/L)	4 weeks
Calcium	Change from baseline in calcium (mg/dL)	4 weeks
Blood Urea Nitrogen (BUN)	Change from baseline in blood urea nitrogen (BUN) (mg/dL)	4 weeks
Magnesium	Change from baseline in magnesium (mg/dL)	4 weeks
Creatinine	Change from baseline in creatinine (mg/dL)	4 weeks
PAGI-SYM Severity Index: Gastroparesis Cardinal Symptom Index (GCSI) Score	PAGI-SYM Severity index: Gastroparesis Cardinal Symptom Index (GCSI) score is the average of 3 subscores: Nausea (average of 3 items: nausea, retching, and vomiting), Fullness/Early Satiety (average of 4 items: stomach fullness, not able to finish normal size meal, feeling excessively full after meals, and loss of appetite), and Bloating (average if 2 items: bloating and stomach visibly larger). Each item is the participant's assessment of severity of the symptom during the past 24 hours, where 0=none, 1=very mild, 2=mild, 3=moderate, 4=severe, and 5=very severe. The outcome measure, change from baseline in GCSI score, has a possible range from -5 to +5, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
PAGI-SYM Severity Index: Nausea/Vomiting Severity Subscore	The PAGI-SYM Severity index: Nausea/vomiting severity subscore is the average of 3 items: nausea, retching, and vomiting. Each item is the participant's assessment of severity of the symptom during the past 24 hours, where 0=none, 1=very mild, 2=mild, 3=moderate, 4=severe, and 5=very severe. The range of scores is 0 to 5, where higher scores are considered a worse outcome. The outcome measure, change from baseline in Nausea/vomiting severity subscore, has a possible range from -5 to +5, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
PAGI-SYM Severity Index: Fullness/Early Satiety Subscore	The PAGI-SYM Severity index: Fullness/Early Satiety Subscore is the average of 4 items: stomach fullness, not able to finish normal size meal, felling excessively full after meals, and loss of appetite. Each item is the participant's assessment of severity of the symptom during the past 24 hours, where 0=none, 1=very mild, 2=mild, 3=moderate, 4=severe, and 5=very severe. The range of scores is 0 to 5, where higher scores are considered a worse outcome. The outcome measure, change from baseline in Fullness/Early Satiety Subscore, has a possible range from -5 to +5, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
PAGI-SYM Severity Index: Bloating Subscore	The PAGI-SYM Severity index: Bloating Subscore is the average of 2 items: bloating (feeling like you need to loosen your clothes) and stomach visibly larger. Each item is the participant's assessment of severity of the symptom during the past 24 hours, where 0=none, 1=very mild, 2=mild, 3=moderate, 4=severe, and 5=very severe. The outcome measure, change from baseline in Bloating Subscore, has a possible range from -5 to +5, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
PAGI-SYM Severity Index: Upper Abdominal Pain Subscore	The PAGI-SYM Severity index: Upper Abdominal Pain subscore is the average of 2 items (upper abdominal pain, upper abdominal discomfort). Each item is the participant's assessment of severity of the symptom during the past 24 hours, where 0=none, 1=very mild, 2=mild, 3=moderate, 4=severe, and 5=very severe. The range of scores is 0 to 5, where higher scores are considered a worse outcome. The outcome measure, change from baseline in Upper Abdominal Pain Subscore, has a possible range from -5 to +5, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
PAGI-SYM Severity Index: GERD Subscore	PAGI-SYM Severity index: Gastroesophageal Reflux (GERD) Subscore is the average of 7 items (heartburn during day, heartburn lying down, chest discomfort day, chest discomfort during sleep, regurgitation during day, regurgitation lying down, bitter taste in mouth). Each item is the participant's assessment of severity of the symptom, where 0=none, 1=very mild, 2=mild, 3=moderate, 4=severe, and 5=very severe. The range of scores is 0 to 5, where higher scores are considered a worse outcome. The outcome measure, change from baseline in GERD Subscore, has a possible range from -5 to +5, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
PAGI-SYM Severity Index: Nausea Severity	The PAGI-SYM Severity index: Nausea severity is the participant's assessment of nausea (feeling sick to your stomach as if you were going to vomit or throw up) during the past 24 hours, where 0=none, 1=very mild, 2=mild, 3=moderate, 4=severe, and 5=very severe. The range of scores is 0 to 5, where higher scores are considered a worse outcome. The outcome measure, change from baseline in Nausea Severity, has a possible range from -5 to +5, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
PAGI-SYM Severity Index: Vomiting Severity	The PAGI-SYM Severity index: Vomiting Severity is the participant's assessment of vomiting during the past 24 hours, where 0=none, 1=very mild, 2=mild, 3=moderate, 4=severe, and 5=very severe. The range of scores is 0 to 5, where higher scores are considered a worse outcome. The outcome measure, change from baseline in Vomiting Severity, has a possible range from -5 to +5, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
PAGI-SYM Severity Index: Retching Severity	The PAGI-SYM Severity index: Retching Severity is the participant's assessment of retching (heaving as if to vomit, but nothing comes up) during the past 24 hours, where 0=none, 1=very mild, 2=mild, 3=moderate, 4=severe, and 5=very severe. The range of scores is 0 to 5, where higher scores are considered a worse outcome. The outcome measure, change from baseline in Retching Severity, has a possible range from -5 to +5, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
PAGI-SYM Severity Index: Stomach Fullness Severity	PAGI-SYM Severity index: Stomach Fullness severity is the participant's assessment of stomach fullness during the past 24 hours, where 0=none, 1=very mild, 2=mild, 3=moderate, 4=severe, and 5=very severe. The range of scores is 0 to 5, where higher scores are considered a worse outcome. The outcome measure, change from baseline in Stomach Fullness severity, has a possible range from -5 to +5, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
PAGI-SYM Severity Index: Unable to Finish Meal Severity	PAGI-SYM Severity index: Unable to Finish Meal severity is the participant's assessment of being unable to finish a normal size meal during the past 24 hours, where 0=none, 1=very mild, 2=mild, 3=moderate, 4=severe, and 5=very severe. The range of scores is 0 to 5, where higher scores are considered a worse outcome. The outcome measure, change from baseline in Unable to Finish Meal severity, has a possible range from -5 to +5, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
PAGI-SYM Severity Index: Excessive Fullness Severity	PAGI-SYM Severity index: Excessive fullness severity is the participant's assessment of feeling excessively full after meals during the past 24 hours, where 0=none, 1=very mild, 2=mild, 3=moderate, 4=severe, and 5=very severe. The range of scores is 0 to 5, where higher scores are considered a worse outcome. The outcome measure, change from baseline in Excessive Fullness severity, has a possible range from -5 to +5, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
PAGI-SYM Severity Index: Loss of Appetite Severity	PAGI-SYM Severity index: Loss of appetite severity is the participant's assessment of loss of appetite during the past 24 hours, where 0=none, 1=very mild, 2=mild, 3=moderate, 4=severe, and 5=very severe. The range of scores is 0 to 5, where higher scores are considered a worse outcome. The outcome measure, change from baseline in Loss of appetite severity, has a possible range from -5 to +5, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
PAGI-SYM Severity Index: Bloating Severity	The PAGI-SYM Severity index: Bloating Severity is the participant's assessment of bloating (feel like you need to loosen your clothes) during the past 24 hours, where 0=none, 1=very mild, 2=mild, 3=moderate, 4=severe, and 5=very severe. The range of scores is 0 to 5, where higher scores are considered a worse outcome. The outcome measure, change from baseline in Bloating Severity, has a possible range from -5 to +5, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
PAGI-SYM Severity Index: Stomach Distention Severity	The PAGI-SYM Severity index: Stomach distention severity is the participant's assessment of stomach distention (stomach or belly visibly larger) during the past 24 hours, where 0=none, 1=very mild, 2=mild, 3=moderate, 4=severe, and 5=very severe. The range of scores is 0 to 5, where higher scores are considered a worse outcome. The outcome measure, change from baseline in Stomach Distention severity, has a possible range from -5 to +5, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
PAGI-SYM Severity Index: Upper Abdominal Pain Severity	The PAGI-SYM Severity index: Upper Abdominal Pain severity is the participant's assessment of upper abdominal pain (above the navel) during the past 24 hours, where 0=none, 1=very mild, 2=mild, 3=moderate, 4=severe, and 5=very severe. The range of scores is 0 to 5, where higher scores are considered a worse outcome. The outcome measure, change from baseline in Upper Abdominal Pain severity, has a possible range from -5 to +5, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
PAGI-SYM Severity Index: Upper Abdominal Discomfort Severity	The PAGI-SYM Severity index: Upper Abdominal Discomfort severity is the participant's assessment of upper abdominal discomfort (above the navel) during the past 24 hours, where 0=none, 1=very mild, 2=mild, 3=moderate, 4=severe, and 5=very severe. The range of scores is 0 to 5, where higher scores are considered a worse outcome. The outcome measure, change from baseline in Upper Abdominal Discomfort severity, has a possible range from -5 to +5, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
PAGI-SYM Severity Index: Lower Abdominal Pain Severity	The PAGI-SYM Severity index: Lower Abdominal Pain severity is the participant's assessment of lower abdominal pain (below the navel) during the past 24 hours, where 0=none, 1=very mild, 2=mild, 3=moderate, 4=severe, and 5=very severe. The range of scores is 0 to 5, where higher scores are considered a worse outcome. The outcome measure, change from baseline in Lower Abdominal Pain severity, has a possible range from -5 to +5, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
PAGI-SYM Severity Index: Lower Abdominal Discomfort Severity	The PAGI-SYM Severity index: Lower Abdominal Discomfort severity is the participant's assessment of lower abdominal discomfort (below the navel) during the past 24 hours, where 0=none, 1=very mild, 2=mild, 3=moderate, 4=severe, and 5=very severe. The range of scores is 0 to 5, where higher scores are considered a worse outcome. The outcome measure, change from baseline in Lower Abdominal Discomfort severity, has a possible range from -5 to +5, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
PAGI-SYM Severity Index: Heartburn During the Day Severity	The PAGI-SYM Severity index: Heartburn during the day severity is the participant's assessment of heartburn (burning pain rising in your chest or throat) during the day over the past 24 hours, where 0=none, 1=very mild, 2=mild, 3=moderate, 4=severe, and 5=very severe. The range of scores is 0 to 5, where higher scores are considered a worse outcome. The outcome measure, change from baseline in Heartburn During the Day severity, has a possible range from -5 to +5, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
PAGI-SYM Severity Index: Heartburn When Lying Down Severity	The PAGI-SYM Severity index: Heartburn when lying down severity is the participant's assessment of heartburn (burning pain rising in your chest or throat) when lying down over the past 24 hours, where 0=none, 1=very mild, 2=mild, 3=moderate, 4=severe, and 5=very severe. The range of scores is 0 to 5, where higher scores are considered a worse outcome. The outcome measure, change from baseline in Heartburn When Lying Down severity, has a possible range from -5 to +5, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
PAGI-SYM Severity Index: Chest Discomfort During the Day Severity	The PAGI-SYM Severity index: Chest discomfort during the day severity is the participant's assessment of feeling of discomfort inside the chest during the day over the past 24 hours, where 0=none, 1=very mild, 2=mild, 3=moderate, 4=severe, and 5=very severe. The range of scores is 0 to 5, where higher scores are considered a worse outcome. The outcome measure, change from baseline in Chest Discomfort During the Day severity, has a possible range from -5 to +5, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
PAGI-SYM Severity Index: Chest Discomfort During Sleep Time Severity	The PAGI-SYM Severity index: Chest discomfort during sleep severity is the participant's assessment of feeling of discomfort inside the chest at night (during sleep time) over the past 24 hours, where 0=none, 1=very mild, 2=mild, 3=moderate, 4=severe, and 5=very severe. The range of scores is 0 to 5, where higher scores are considered a worse outcome. The outcome measure, change from baseline in Chest Discomfort During Sleep Time severity, has a possible range from -5 to +5, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
PAGI-SYM Severity Index: Regurgitation During the Day Severity	The PAGI-SYM Severity index: Regurgitation during the day severity is the participant's assessment of regurgitation or reflux (fluid or liquid from your stomach coming up into throat) during the day over the past 24 hours, where 0=none, 1=very mild, 2=mild, 3=moderate, 4=severe, and 5=very severe. The range of scores is 0 to 5, where higher scores are considered a worse outcome. The outcome measure, change from baseline in Regurgitation During the Day severity, has a possible range from -5 to +5, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
PAGI-SYM Severity Index: Regurgitation When Lying Down Severity	The PAGI-SYM Severity index: Regurgitation when lying down severity is the participant's assessment of regurgitation or reflux (fluid or liquid from your stomach coming up into throat) when lying down over the past 24 hours, where 0=none, 1=very mild, 2=mild, 3=moderate, 4=severe, and 5=very severe. The range of scores is 0 to 5, where higher scores are considered a worse outcome. The outcome measure, change from baseline in Regurgitation When Lying Down severity, has a possible range from -5 to +5, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
PAGI-SYM Severity: Bitter Taste Severity	The PAGI-SYM Severity index: Bitter Taste severity is the participant's assessment of bitter, acid, or sour taste in mouth during the past 24 hours, where 0=none, 1=very mild, 2=mild, 3=moderate, 4=severe, and 5=very severe. The range of scores is 0 to 5, where higher scores are considered a worse outcome. The outcome measure, change from baseline in Bitter Taste Severity score, has a possible range from -5 to +5, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
PAGI-SYM Severity Index: Constipation Severity	The PAGI-SYM Severity index: Constipation severity is the participant's assessment of constipation during the past 24 hours, where 0=none, 1=very mild, 2=mild, 3=moderate, 4=severe, and 5=very severe. The range of scores is 0 to 5, where higher scores are considered a worse outcome. The outcome measure, change from baseline in Constipation Severity score, has a possible range from -5 to +5, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
PAGI-SYM Severity Index: Diarrhea Severity	The PAGI-SYM Severity index: Diarrhea severity is the participant's assessment of constipation during the past 24 hours, where 0=none, 1=very mild, 2=mild, 3=moderate, 4=severe, and 5=very severe. The range of scores is 0 to 5, where higher scores are considered a worse outcome. The outcome measure, change from baseline in Diarrhea Severity score, has a possible range from -5 to +5, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
Gastrointestinal Symptom Rating Scale (GSRS): Total Score	The Gastrointestinal Symptom Rating Scale (GSRS) is a 15-item questionnaire for participants with gastrointestinal discomfort. The GSRS Total Score is the average of the 15 items. Each item is rated on a 0 to 7 scale, where 0 indicates no discomfort and 7 indicates very severe discomfort. The range of scores is 0 to 7, where higher scores are considered a worse outcome.The outcome measure, change from baseline in GSRS Total Score, has a possible range from -7 to +7, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
Gastrointestinal Symptom Rating Scale (GSRS): Reflux Score	The Gastrointestinal Symptom Rating Scale (GSRS) is a 15-item questionnaire for participants with gastrointestinal discomfort. The GSRS Reflux Score is a measure of how bothered the participant has been by acid reflux during the past week. The range of scores is 0 to 7, where 0 indicates no discomfort and 7 indicates very severe discomfort. Higher scores are considered a worse outcome.The outcome measure, change from baseline in GSRS Reflux Score, has a possible range from -7 to +7, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
Gastrointestinal Symptom Rating Scale (GSRS): Abdominal Pain Score	The Gastrointestinal Symptom Rating Scale (GSRS) is a 15-item questionnaire for participants with gastrointestinal discomfort. The GSRS Abdominal Pain Score is a measure of how bothered the participant has been by pain or discomfort in the upper abdomen or pit of the stomach during the past week. The range of scores is 0 to 7, where 0 indicates no discomfort and 7 indicates very severe discomfort. Higher scores are considered a worse outcome.The outcome measure, change from baseline in GSRS Abdominal Pain Score, has a possible range from -7 to +7, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 week
Gastrointestinal Symptom Rating Scale (GSRS): Indigestion Score	The Gastrointestinal Symptom Rating Scale (GSRS) is a 15-item questionnaire for participants with gastrointestinal discomfort. The GSRS Indigestion Score is a measure of how bothered the participant has been by indigestion during the past week. The range of scores is 0 to 7, where 0 indicates no discomfort and 7 indicates very severe discomfort. Higher scores are considered a worse outcome.The outcome measure, change from baseline in GSRS Indigestion Score, has a possible range from -7 to +7, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
Gastrointestinal Symptom Rating Scale (GSRS): Diarrhea Score	The Gastrointestinal Symptom Rating Scale (GSRS) is a 15-item questionnaire for participants with gastrointestinal discomfort. The GSRS Diarrhea Score is a measure of how bothered the participant has been by diarrhea during the past week. The range of scores is 0 to 7, where 0 indicates no discomfort and 7 indicates very severe discomfort. Higher scores are considered a worse outcome.The outcome measure, change from baseline in GSRS Diarrhea Score, has a possible range from -7 to +7, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
Gastrointestinal Symptom Rating Scale (GSRS): Constipation Score	The Gastrointestinal Symptom Rating Scale (GSRS) is a 15-item questionnaire for participants with gastrointestinal discomfort. The GSRS Constipation Score is a measure of how bothered the participant has been by constipation during the past week. The range of scores is 0 to 7, where 0 indicates no discomfort and 7 indicates very severe discomfort. Higher scores are considered a worse outcome.The outcome measure, change from baseline in GSRS Constipation Score, has a possible range from -7 to +7, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
Brief Pain Inventory: Severity Score	The Brief Pain Inventory: Severity Score is the average of four questions in which the participant rates his or her pain: the worse pain in the past 24 hours, the least pain in the past 24 hours, average pain, and pain right now. The range of possible scores is 0 to 10, with higher scores indicating more severe pain. The outcome measure, change from baseline in Brief Pain Inventory Severity Score, has a possible range from -10 to +10, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
Brief Pain Inventory: Interference Score	The Brief Pain Inventory: Interference Score is the average of seven questions in which the participant rates the degree to which his or her pain interferes with daily functions and mood: general activity, mood, walking ability, normal work, relationships, sleep, enjoyment of life. The range of possible scores is 0 to 10, with higher scores indicating more interference caused by pain. The outcome measure, change from baseline in Brief Pain Inventory Interference Score, has a possible range from -10 to +10, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
Beck Depression Inventory (BDI) Score	The Beck Depression Inventory (BDI) survey is comprised of 21 multiple choice questions that relate to depression, cognition, and physical well-being and is used to quantify depression. The BDI total score is the sum of the 21 items, where each item ranges from 0 to 3 (lower scores are less severe, higher scores are more severe). The range for the BDI total score is 0 to 63, where lower scores indicate less depression and higher scores indicate more severe depression. The outcome measure, change from baseline in BDI score, has a possible range from -63 to +63, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
State-Trait Anxiety Inventory (STAI): State Anxiety Score	The State-Trait Anxiety Inventory (STAI): State anxiety score is the sum of scores from 20 questions relating to state anxiety, which is a temporary state varying in intensity. The possible range of scores is from 20 to 80, with increasing scores considered a worse outcome. The outcome measure, change from baseline in STAI State Anxiety score, has a possible range from -60 to +60, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
State-Trait Anxiety Inventory (STAI): Trait Anxiety Score	The State-Trait Anxiety Inventory (STAI): Trait anxiety score is the sum of scores from 20 questions pertaining to trait anxiety, which is a general propensity to be anxious. The possible range of scores is from 20 to 80, with increasing scores considered a worse outcome. The outcome measure, change from baseline in STAI Trait Anxiety score, has a possible range from -60 to +60, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.	4 weeks
Satiety Test, Volume Consumed	The Satiety Test measures the total volume of liquid (Ensure) that the participant is able to consume. The participant drinks 150 mL of Ensure every 5 minutes until he/she is completely full. The outcome measure is the change from baseline in volume of liquid (Ensure) consumed (mL), where positive values indicate a positive outcome (improvement).	4 weeks
Electrogastrography (EGG): Bradygastria (1-<2.5 Cpm) at 4 Weeks, Baseline Measurement	Electrogastrography (EGG) is a test which records the electrical pacemaking signals that travel through the stomach muscles and control the muscles' contractions. Normal pacing is considered 2.5-3.7 cycles per minute (cpm). Bradygastria is when the rate of electrical activity in the stomach is <2.5 cycles per minute for at least 1 minute (a decrease in electrical activity in the stomach). The average power in frequency region is the percentage of time that the dominant EGG frequencies are in a given frequency: bradygastria, normal, tachygastria, or duodenal. The outcome measure is the change from baseline (here, baseline refers to the test performed during screening, not the baseline value of the EGG test) in percent of time with frequencies in the ranges, where negative values for bradygastria indicate improvement (less time in a dysrhythmic state).	4 weeks
Electrogastrography (EGG): Bradygastria (1-<2.5 Cpm) at 4 Weeks, 0-30 Post-satiety Measurement	Electrogastrography (EGG) is a test which records the electrical pacemaking signals that travel through the stomach muscles and control the muscles' contractions. The 0-30 post-satiety measurement of the test is that taken 30 minutes after the participant consumes Ensure until feeling completely full. Normal pacing is considered 2.5-3.7 cycles per minute (cpm). Bradygastria is when the rate of electrical activity in the stomach is <2.5 cycles per minute for at least 1 minute. Average power in frequency region is the % of time that the dominant EGG frequencies are in a given frequency: bradygastria, normal, tachygastria, or duodenal. The outcome measure is the change from baseline (baseline refers to test performed during screening, not baseline value of the EGG test) in % of time with frequencies in the ranges. Negative values for bradygastria indicate improvement (less time in a dysrhythmic state).	4 weeks
Electrogastrography (EGG): Normogastria (2.5-<3.8 Cpm) at 4 Weeks, Baseline Measurement	Electrogastrography (EGG) is a test which records the electrical pacemaking signals that travel through the stomach muscles and control the muscles' contractions. Normal pacing (normogastria) is considered 2.5-3.7 cycles per minute (cpm). The average power in frequency region is the percentage of time that the dominant EGG frequencies are in a given frequency: bradygastria, normal, tachygastria, or duodenal. The outcome measure is the change from baseline (here, baseline refers to the test performed during screening, not the baseline value of the EGG test) in percent of time with frequencies in the ranges, where positive values for normal rates indicate an increase in the normal pacing (improvement).	4 weeks
Electrogastrography (EGG): Normogastria (2.5-<3.8 Cpm) at 4 Weeks, 0-30 Post-satiety Measurement	Electrogastrography (EGG) is a test which records the electrical pacemaking signals that travel through the stomach muscles and control the muscles' contractions. The 0-30 post-satiety measurement that taken 30 minutes after the participant consumes Ensure until feeling completely full. Normal pacing (normogastria) is considered 2.5-3.7 cycles per minute (cpm). The average power in frequency region is the percentage of time that the dominant EGG frequencies are in a given frequency: bradygastria, normal, tachygastria, or duodenal. The outcome measure is the change from baseline (baseline refers to the test performed during screening, not the baseline value of the EGG test) in percent of time with frequencies in the ranges, where positive values for normal rates indicate an increase in the normal pacing (improvement).	4 weeks
Electrogastrography (EGG): Tachygastria (3.8-10 Cpm) at 4 Weeks, Baseline Measurement	Electrogastrography (EGG) is a test which records the electrical pacemaking signals that travel through the stomach muscles and control the muscles' contractions. Normal pacing is considered 2.5-3.7 cycles per minute (cpm). Tachygastria is when the rate of electrical activity in the stomach is 3.8-10 cycles per minute for at least 1 minute (an increase in electrical activity in the stomach). The average power in frequency region is the percentage of time that the dominant EGG frequencies are in a given frequency: bradygastria, normal, tachygastria, or duodenal. The outcome measure is the change from baseline (here, baseline refers to the test performed during screening, not the baseline value of the EGG test) in percent of time with frequencies in the ranges, where negative values for tachygastria indicate improvement (less time in a dysrhythmic state).	4 weeks
Electrogastrography (EGG): Tachygastria (3.8-10 Cpm) at 4 Weeks, 0-30 Post-satiety Measurement	Electrogastrography (EGG) is a test which records the electrical pacemaking signals that travel through the stomach muscles and control the muscles' contractions. The 0-30 post-satiety measurement that taken 30 minutes after the participant consumes Ensure until feeling completely full. Normal pacing is considered 2.5-3.7 cycles per minute (cpm). Tachygastria is when the rate of electrical activity in the stomach is 3.8-10 cycles per minute for at least 1 minute (an increase in electrical activity in the stomach). The average power in frequency region is the percentage of time that the dominant EGG frequencies are in a given frequency: bradygastria, normal, tachygastria, or duodenal. The outcome measure is the change from baseline (here, baseline refers to the test performed during screening, not the baseline value of the EGG test) in percent of time with frequencies in the ranges, where negative values for tachygastria indicate improvement (less time in a dysrhythmic state).	4 weeks
Electrogastrography (EGG): Duodenal (>10-15 Cpm) at 4 Weeks, Baseline Measurement	Electrogastrography (EGG) is a test which records the electrical pacemaking signals that travel through the stomach muscles and control the muscles' contractions. Normal pacing is considered 2.5-3.7 cycles per minute (cpm). Duodenal is when the rate of electrical activity in the stomach is >10-15 cycles per minute for at least 1 minute. The average power in frequency region is the percentage of time that the dominant EGG frequencies are in a given frequency: bradygastria, normal, tachygastria, or duodenal. The outcome measure is the change from baseline (here, baseline refers to the test performed during screening, not the baseline value of the EGG test) in percent of time with frequencies in the ranges, where negative values for duodenal indicate improvement (less time in a dysrhythmic state).	4 weeks
Electrogastrography (EGG): Duodenal (>10-15 Cpm) at 4 Weeks, 0-30 Post-satiety Measurement	Electrogastrography (EGG) is a test which records the electrical pacemaking signals that travel through the stomach muscles and control the muscles' contractions. The 0-30 post-satiety measurement that taken 30 minutes after the participant consumes Ensure until feeling completely full. Normal pacing is considered 2.5-3.7 cycles per minute (cpm). Duodenal is when the rate of electrical activity in the stomach is >10-15 cycles per minute for at least 1 minute. The average power in frequency region is the percentage of time that the dominant EGG frequencies are in a given frequency: bradygastria, normal, tachygastria, or duodenal. The outcome measure is the change from baseline (here, baseline refers to the test performed during screening, not the baseline value of the EGG test) in percent of time with frequencies in the ranges, where negative values for duodenal indicate improvement (less time in a dysrhythmic state).	4 weeks

Collaborators and Investigators

• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Publications and helpful links

General Publications

• Pasricha PJ, Yates KP, Sarosiek I, McCallum RW, Abell TL, Koch KL, Nguyen LAB, Snape WJ, Hasler WL, Clarke JO, Dhalla S, Stein EM, Lee LA, Miriel LA, Van Natta ML, Grover M, Farrugia G, Tonascia J, Hamilton FA, Parkman HP; NIDDK Gastroparesis Clinical Research Consortium (GpCRC). Aprepitant Has Mixed Effects on Nausea and Reduces Other Symptoms in Patients With Gastroparesis and Related Disorders. Gastroenterology. 2018 Jan;154(1):65-76.e11. doi: 10.1053/j.gastro.2017.08.033. Epub 2017 Oct 28.

Helpful Links

• Gastroparesis Clinical Research Consortium website

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: June 22, 2010
• First Submitted That Met QC Criteria: June 22, 2010
• First Posted (Estimate): June 23, 2010

Study Record Updates

• Last Update Posted (Actual): May 8, 2019
• Last Update Submitted That Met QC Criteria: April 15, 2019
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: nausea; vomiting; gastroparesis
• Additional Relevant MeSH Terms: Digestive System Diseases; Neurologic Manifestations; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Stomach Diseases; Paralysis; Nausea; Vomiting; Gastroparesis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Neurokinin-1 Receptor Antagonists; Aprepitant
• Other Study ID Numbers: IND - DK-GpCRC-4APRON; U01DK073983 (U.S. NIH Grant/Contract); U01DK073975 (U.S. NIH Grant/Contract); U01DK074035 (U.S. NIH Grant/Contract); U01DK074007 (U.S. NIH Grant/Contract); U01DK073974 (U.S. NIH Grant/Contract); U01DK073985 (U.S. NIH Grant/Contract); U01DK074008 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be deposited with the NIDDK Data Repository at the end of the funding cycle.
• IPD Sharing Time Frame: The primary analysis analytic dataset will be available at the NIDDK Central Repository approximately 6 months after publication. The complete study dataset is due approximately 2 years post study publication.
• IPD Sharing Access Criteria: The NIDDDK Central Repository staff is responsible for review of requests for use of the APRON public access datasets. A NIDDK SDUC form must be submitted.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ANALYTIC_CODE; CSR