Olanzapine for the Treatment of Refractory Chronic Nausea and Vomiting

Prospective, observational study evaluating the effect of olanzapine for the treatment of refractory chronic nausea and vomiting.

Study Overview

• Status: Withdrawn
• Conditions: Nausea; Vomiting
• Intervention / Treatment: Drug: Olanzapine

Detailed Description

Patients will be identified who are seen in the Johns Hopkins Gastroenterology Clinic, suffer from chronic nausea and vomiting that is refractory to both prokinetic and antiemetic medications, and are being prescribed olanzapine for treatment of nausea and vomiting. Patients who meet criteria will be enrolled and their gastrointestinal symptoms, quality of life, and psychological symptoms will be assessed by various questionnaires and followed over the course of 3 months.

• Study Type: Observational

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adult patients who are seen in the Johns Hopkins Center for Neurogastroenterology, have been identified by the healthcare provider (physician, nurse practitioner, physician assistant) as having refractory chronic nausea and vomiting that has failed a trial of typical treatments (both anti-emetics and pro kinetics), and who will be prescribed olanzapine for the treatment of chronic nausea and vomiting

Description

Inclusion Criteria:

• 18-65 years of age
• Able to communicate in English without aid of interpreter

• Have chronic refractory nausea, meeting each of the following criteria:

  1. Baseline nausea and vomiting score on VAS of 25mm or greater
  2. Duration symptoms of at least 6 months (does not have to be contiguous)
  3. Intolerance to or inadequate response to prior treatment with both 1) ondansetron or another serotonin (5HT3) antagonist and 2) metoclopramide or domperidone

Exclusion Criteria:

• History of chemotherapy within the last year
• Current diagnosis of cancer
• Pregnant or breastfeeding
• For females, active efforts to conceive/become pregnant during the time of the study
• Chronic opioid use (3 times a week or greater use)
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevation of greater than 2x upper limit of normal (within 3 months of enrollment)
• Cirrhosis
• Unable or unwilling to stop using metoclopramide while using olanzapine
• Concomitant use of other antipsychotics (e.g., haloperidol)
• Prolonged corrected QT interval (QTc) (>470ms for men and >480ms for women)
• History of life-threatening arrhythmia
• Hypokalemia (potassium <3.1) or hypomagnesemia (magnesium <1.2)
• Metabolic syndrome, defined as per Adult Treatment Panel III criteria
• Granulocytopenia (absolute neutrophil count <1500)
• History of tardive dyskinesia
• History of acute dystonic reaction to medications
• History of neuroleptic malignant syndrome

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nausea and vomiting severity	Effect of olanzapine on refractory nausea and vomiting as per changes in patient scoring of the severity of nausea and vomiting on a daily visual analog scale (VAS). Scores range from 0-100, with higher scores indicating more severe symptoms.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of upper gastrointestinal symptoms	The effect of olanzapine on severity of upper gastrointestinal symptoms, assessed by the NIH Patient-Reported Outcomes Measurement Information System (PROMIS) Gastrointestinal Symptom Scales questionnaire. The questionnaire is 60-item GI symptom questionnaire covering 8 domains: Gastroesophageal reflux (13 items), disrupted swallowing (7 items), diarrhea (5 items), bowel incontinence/soilage (4 items), nausea and vomiting (4 items), constipation (9 items), belly pain (6 items), and gas/bloat/flatulence (12 items). Higher scores indicate more severe symptoms. A scoring service is used to convert the raw scores to a final T-score.	3 months
Quality of life and functional status	The effect of olanzapine on quality of life and functional status, assessed by the EuroQol 5 Dimension (EQ-5D) questionnaire. The EQ-5D descriptive system consists of five dimensions: Mobility, Self-care, Usual activities, Pain/discomfort, Anxiety/depression. Scores range from 5-25, with higher scores indicating more severe symptoms/decreased quality of life.	3 months
Symptom-specific anxiety	The effect of olanzapine on patient's overall gastrointestinal symptom-specific anxiety, assessed by the Visceral Sensitivity Index (VSI) questionnaire. The VSI is an instrument to assess gastrointestinal-specific anxiety, the cognitive, affective, and behavioral response to fear of gastrointestinal sensations, symptoms, and the context in which these visceral sensations and symptoms occur. The questionnaire consists of 15 questions, each scored 1-6. Total scores range from 15-90, with lower scores indicating more severe symptoms.	3 months
Presence of depression	Presence of depression in participants both before initiating olanzapine and after starting olanzapine, assessed by the Patient Health Questionnaire (PHQ-4) at baseline, 1 month, and 3 months. Total score is determined by adding together the scores for each of the 4 items. Scores range from 0-12 and are rated as normal (0-2), mild depression (3-5), moderate depression (6-8), and severe depression (9-12).	3 months

Collaborators and Investigators

• Sponsor: Johns Hopkins University

Study record dates

Study Major Dates

• Study Start: November 1, 2016
• Primary Completion (ACTUAL): December 1, 2017
• Study Completion (ACTUAL): December 1, 2017

Study Registration Dates

• First Submitted: November 28, 2016
• First Submitted That Met QC Criteria: November 28, 2016
• First Posted (ESTIMATE): November 30, 2016

Study Record Updates

• Last Update Posted (ACTUAL): August 20, 2018
• Last Update Submitted That Met QC Criteria: August 16, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Nausea; Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Olanzapine
• Other Study ID Numbers: IRB00037144