Efficacy and Safety of Cannabidiol for Gastroparesis and Functional Dyspepsia

Pharmacodynamics, Pharmacogenetics, Clinical Efficacy and Safety of Cannabidiol for Gastroparesis and Functional Dyspepsia

Researchers are looking at the effects of a cannabidiol medication on stomach function in people with gastroparesis (a paralyzed stomach) and people with dyspepsia (an upset stomach caused by improper functioning of the stomach's muscles or nerves).

Study Overview

• Status: Completed
• Conditions: Dyspepsia; Gastroparesis
• Intervention / Treatment: Drug: Cannabidiol; Other: placebo

• Study Type: Interventional
• Enrollment (Actual): 92
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Maggie Breen-Lyles; Phone Number: (507) 293-0237; Email: Breen-Lyles.Margaret@mayo.edu
• Study Contact Backup: Name: Ann Taylor; Phone Number: (507) 266-3421; Email: Taylor.Ann@mayo.edu

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with gastroparesis or functional dyspepsia (FD)
• Age 18-70 years
• Patients will be identified from among Mayo Clinic patients.

• Patients will have symptoms consistent with gastroparesis based on a national guideline for gastroparesis (symptoms plus delayed gastric emptying of solids). Patients with Rome IV criteria for postprandial distress syndrome (a subset of functional dyspepsia) will be selected based on gastric emptying of solids which is NOT delayed, in addition to standard FD criteria:

  • Symptoms fulfilled for the last 3 months with onset greater than 6 months before diagnosis:
  • One or more symptoms being bothersome: postprandial fullness, early satiation, epigastric pain or burning
  • Must include one or both of the following at least 3 days per week: bothersome postprandial fullness (i.e., severe enough to impact on usual activities) or bothersome early satiation (i.e., severe enough to prevent finishing a regular-size meal)
  • No evidence of organic, systemic, or metabolic disease to explain the symptoms on routine investigations.
  • Participants will have previously undergone test of gastric emptying of solids using the standardized Mayo Clinic scintigraphic method
• Ability to provide informed consent
• Absence of other diseases (structural or metabolic) which could interfere with interpretation of the study results
• Body mass index of 18-35 kg/m2
• Several medication classes, particularly those affecting gastrointestinal transit or motor functions, will be excluded, including GLP-1 receptor or amylin agonists in patients with diabetes mellitus. Stable doses of thyroid replacement, estrogen replacement, low-dose aspirin for cardioprotection, and birth control (but with adequate backup contraception, as drug interactions with birth control have not been conducted for secretin PAM) are

Exclusion Criteria:

• Patients with current H. pylori infection will be excluded.
• Pregnancy or lactation
• Rapid metabolizers for CYP3A4 or CYP2C19 [estimated prevalence of 17% and 18% respectively
• based on literature review will be excluded since this could impact assessment of effects of cannabidiol
• Patients with abnormal baseline liver transaminases (any value above UNL), since up to 3-fold, dose-related elevations of liver transaminases (ALT and/or AST) occur in 13% of treated patients (vs. 1% placebo);
• Hypersensitivity to cannabidiol or any of the ingredients in EPIDIOLEX
• Concomitant use of valproate, central nervous system (CNS) depressants and alcohol, other hepatotoxic drugs

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Pharmacodynamics and clinical effects of cannabidiol; Cannabidiol will be administered orally twice daily in equally divided doses starting at 2.5mg/kg per day and increasing by 2.5 to 5.0mg/kg every other day until the target dose of 20mg/kg is reached. Cannabidiol and the matching placebo solution (excipients alone) will be provided in identical 100ml amber glass bottles. At the end of the treatment period, the treatment solutions will be tapered (10% volume each day) over 10 days.	Drug: Cannabidiol; Cannabidiol and the matching placebo solution (excipients alone) will be provided in identical 100ml amber glass bottles. At the end of the treatment period, the treatment solutions will be tapered (10% volume each day) over 10 days. In accordance with Food and Drug Administration guidance, prior to starting treatment and at end of 1 month treatment, we shall obtain serum transaminases (alanine and aspartate) and total bilirubin levels. These tests will also be performed if patient develops clinical signs or symptoms suggestive of hepatic dysfunction (e.g., unexplained nausea, vomiting, right upper quadrant abdominal pain, fatigue, anorexia, or jaundice and/or dark urine); if such features develop the treatment will be interrupted or discontinued.
Placebo Comparator: pharmacodynamics and clinical effects of placebo; Placebo will be administered orally twice daily in equally divided doses starting at 2.5mg/kg per day and increasing by 2.5 to 5.0mg/kg every other day until the target dose of 20mg/kg is reached. Cannabidiol and the matching placebo solution (excipients alone) will be provided in identical 100ml amber glass bottles. At the end of the treatment period, the treatment solutions will be tapered (10% volume each day) over 10 days.	Other: placebo; Cannabidiol and the matching placebo solution (excipients alone) will be provided in identical 100ml amber glass bottles. At the end of the treatment period, the treatment solutions will be tapered (10% volume each day) over 10 days. In accordance with Food and Drug Administration guidance, prior to starting treatment and at end of 1 month treatment, we shall obtain serum transaminases (alanine and aspartate) and total bilirubin levels. These tests will also be performed if patient develops clinical signs or symptoms suggestive of hepatic dysfunction (e.g., unexplained nausea, vomiting, right upper quadrant abdominal pain, fatigue, anorexia, or jaundice and/or dark urine); if such features develop the treatment will be interrupted or discontinued.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gastric Emptying Half-time (T1/2) of Solids	Subjects ingested a Technetium-99m sulfur colloid radiolabeled meal and Indium-111 absorbed on to activated charcoal particles and delivered to the colon by an oral methacrylate-coated capsule. Gastric emptying (GE t 1/2) was measured by scintigraphy and defined as the time required for 50% of the radiolabeled tracer to empty from the stomach.	4 weeks
Gastric Emptying Lag Time (T-lag) of Solids	Subjects ingested a Technetium-99m sulfur colloid radiolabeled meal and Indium-111 absorbed on to activated charcoal particles and delivered to the colon by an oral methacrylate-coated capsule. Gastric emptying lag time (GE t-lag) was measured by scintigraphy and defined as the amount of time the radioactive meal was in the stomach before starting to empty into the small bowel.	4 weeks
Fasting Gastric Volume	Gastric fasting volume was measured prior to a meal of 300 mL standardized radio-labeled Ensure drink using an intravenous injection of Technetium Tc-99m pertechnetate and noninvasive single photon emission-computed tomography (SPECT).	4 weeks
Gastric Accommodation	Gastric accommodation was measured 15 minutes after ingestion of 300 mL standardized radio-labeled Ensure drink using an intravenous injection of Technetium Tc-99m pertechnetate and noninvasive single photon emission-computed tomography (SPECT).	4 weeks
Satiation Volume to Fullness	Thirty (30) minutes after ingesting the meal of 300 mL radio-labeled Ensure drink, an additional Ensure drink was ingested at a constant rate of 30 mL/min. Participants recorded their sensations every 5 minutes using a numeric scale from 0 to 5, with level 0 being no symptoms, level 3 corresponding to fullness sensation after a typical meal, and level 5 corresponding to the MTV (maximum or unbearable fullness/satiation). Nutrient intake was stopped when subjects reach a score of 5.	4 weeks
Satiation Maximum Tolerated Volume (MTV)	Thirty (30) minutes after ingesting the meal of 300 mL radio-labeled Ensure drink, an additional Ensure drink was ingested at a constant rate of 30 mL/min. Participants recorded their sensations every 5 minutes using a numeric scale from 0 to 5, with level 0 being no symptoms, level 3 corresponding to fullness sensation after a typical meal, and level 5 corresponding to the MTV (maximum or unbearable fullness/satiation). Nutrient intake was stopped when subjects reach a score of 5.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weekly Global Symptom Assessment	The number of functional dyspepsia participants who confirmed adequate relief of dyspepsia symptoms, based on the self-reporting question "In the past 7 days have you had adequate relief of your upper abdominal pain or discomfort?".	4 weeks
Mean Daily Symptom Score in Functional Dyspepsia	Self-reported daily symptom diaries assessed 3 symptoms of functional dyspepsia: (1) upper abdominal pain, (2) nausea, and (3) bloating or distension. Each symptom was scored from 0-4, where 0=none, 1= very mild, 2=mild, 3=moderate, and 4=severe. The responses were averaged together to provide an overall symptom score, which ranged from 0-4, where a higher score reflects worse symptoms.	4 weeks
Mean Daily Epigastric Pain in Functional Dyspepsia	Mean daily epigastric pain in functional dyspepsia participants as measured by the question "How much did you suffer from pain in your stomach area today?". The score is based on 5 point scale ranging from 0 (not at all) to 5 (extremely) where a higher score reflects more pain.	4 weeks
Quality of Life in Functional Dyspepsia	The Nepean Dyspepsia Index (NDI) is used to assess functional dyspepsia quality of life. NDI scores are summarized as overall quality of life based on 5 subscales: interference, knowledge/control, eating/drinking, sleep disturbance, work/study. There are two questions per subscale for a total of 10 questions. Each question is ranked from 0-4, where 0 is 'not at all' and 4 is 'extremely'. The results from each question are added together to generate a total index score of 0 to 40. A lower score reflects no to little impact functional dyspepsia has on on quality of life while a higher score reflects significant impact functional dyspepsia has on quality of life.	4 weeks
Aggregate Symptom Score	Postprandial symptoms of fullness, nausea, bloating, and pain were measured 30min after the satiation drink test using 100mm horizontal visual analog scales, with the words "none" and "worst ever" anchored at each end. Scores for each symptom were added to calculate the aggregate symptom score, which ranged from 0-400, where a lower score reflected mild symptoms and a higher score reflected more severe symptoms.	4 weeks
Overall Severity in Gastroparesis	Overall severity in gastroparesis was self-measured daily by asking the question "In thinking about your gastroparesis disorder, what was the overall severity of your gastroparesis symptoms today (during the past 24 hours)"? The responses were ranked as 0 (none), 1 (mild), 2 (moderate), 3 (severe) and 4 (very severe). Scores range from 0-4, where 0 reflects little to no severity of symptoms and 4 reflects severe symptoms.	4 weeks
Average Daily Vomiting Episodes in Gastroparesis	The average daily number of vomiting episodes in gastroparesis was measured by participants self-reporting responses to the question "In the past 24 hours how many episodes of vomiting did you have?"	4 weeks

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Michael Camilleri, MD, Mayo Clinic

Publications and helpful links

General Publications

• Atieh J, Maselli D, Breen-Lyles M, Torres M, Katzka D, Ryks M, Busciglio I, Burton D, Carlson P, Harmsen WS, Camilleri M. Cannabidiol for Functional Dyspepsia With Normal Gastric Emptying: A Randomized Controlled Trial. Am J Gastroenterol. 2022 Aug 1;117(8):1296-1304. doi: 10.14309/ajg.0000000000001805. Epub 2022 May 9.

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): September 4, 2019
• Primary Completion (Actual): February 23, 2023
• Study Completion (Actual): February 23, 2023

Study Registration Dates

• First Submitted: May 3, 2019
• First Submitted That Met QC Criteria: May 6, 2019
• First Posted (Actual): May 7, 2019

Study Record Updates

• Last Update Posted (Actual): February 13, 2024
• Last Update Submitted That Met QC Criteria: February 12, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neurologic Manifestations; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Stomach Diseases; Paralysis; Dyspepsia; Gastroparesis; Anticonvulsants; Cannabidiol
• Other Study ID Numbers: 19-002483; R01DK122280 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No