Efficacy and Safety of Cannabidiol for Gastroparesis and Functional Dyspepsia

Study Overview
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Brief Summary
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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).

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

Conditions
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Gastroparesis, Dyspepsia

Intervention / Treatment
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* Drug: Cannabidiol
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with gastroparesis or functional dyspepsia 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 (2) for gastroparesis (symptoms PLUS delayed gastric emptying of solids). Patients with Rome IV criteria for postprandial distress syndrome (a subset of functional dyspepsia) (35) 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 (36)] 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, CNS depressants and alcohol, other hepatotoxic drugs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pharmacodynamics and clinical effects of cannabidiol<br>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<br>* 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.<br>|
| Placebo Comparator: pharmacodynamics and clinical effects of placebo<br>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<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary endpoint gastric accommodation | Fasting gastric and accommodation volumes (mL) measured by SPECT | 4 Weeks | 
| Primary Endpoint satiation | Volume to fullness (VTF, mL) on satiation test | 4 weeks | 
| Primary endpoint Gastric emptying | Gastric emptying T1/2 of solids on scintigraphy, minutes | 4 weeks | 
| Primary endpoint Gastroparesis symptoms | Average weekly gastroparesis cardinal symptom index-daily diary score on treatment in patients with gastroparesis evaluating 6 symptoms (nausea, abdominal distension, bloating, early satiety, vomiting, and abdominal pain) on a 5 point scale ranging from none to very severe | Daily diary over 4 weeks | 
| Primary endpoint functional dyspepsia symptoms | Postprandial distress score on Nepean Dyspepsia Index (one of 10 items each scored on 5 point scale ranging from not at all to extremely in patients with functional dyspepsia | Every 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Endpoint Gastric emptying | Gastric emptying of solids at 2 hours and 4 hours on scintigraphy, % | 4 Weeks | 
| Secondary Endpoint Symptom scores during gastric emptying test | Aggregate symptoms and individual symptom scores under the curve during the 4 hours after the standard meal during the gastric emptying test, measured on 0-100 mm visual; analog scale | over 4 hours at 4 weeks | 
| Secondary Endpoint Satiation | Maximum tolerated volume (mL) and aggregate symptoms (nausea, fullness, bloating, pain on 0-100mm visual analog scale), scored 30min after MTV on satiation | over 2 hour test at week 4 | 
| Secondary Endpoint Gastroparesis symptoms | On weekly gastroparesis cardinal symptom index-daily diary, Individual subscales of GCSI-DD (3 subscales: nausea/vomiting, postprandial fullness/early satiety, and bloating) score in patients with gastroparesis evaluated by a 5 point scale ranging from none to very severe | 4 weeks | 
| Secondary Endpoint: Overall dyspepsia score | Overall Nepean Dyspepsia Index (NDI) score in functional dyspepsia based on 10 items each scored on 5 point scale ranging from not at all to extremely | Every 2 weeks | 
| Secondary Endpoint: Pain score in dyspepsia | Pain based on Nepean Dyspepsia Index (NDI) score based on 5 point scale ranging from not at all to extremely | Every 2 weeks | 
| Secondary Endpoint: Adequate relief response in functional dyspepsia | Single question on adequate relief answered yes or no | 4 weeks | 
| Secondary endpoint: Daily score in functional dyspepsia | Daily Symptom score of upper abdominal pain, nausea and bloating or distension based on 5 point scale (ranging from none to severe) in patients with functional dyspepsia | daily for 4 weeks |