Clinical trial NCT03941288: Efficacy and Safety of Cannabidiol for Gastroparesis and Functional Dyspepsia
Official title: Pharmacodynamics, Pharmacogenetics, Clinical Efficacy and Safety of Cannabidiol for Gastroparesis and Functional Dyspepsia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gastroparesis
Dyspepsia
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2019-05-07
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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

Primary outcomes:
measure: Gastric Emptying Half-time (T1/2) of Solids
timeFrame: 4 weeks
measure: Gastric Emptying Lag Time (T-lag) of Solids
timeFrame: 4 weeks
measure: Fasting Gastric Volume
timeFrame: 4 weeks
measure: Gastric Accommodation
timeFrame: 4 weeks
measure: Satiation Volume to Fullness
timeFrame: 4 weeks
measure: Satiation Maximum Tolerated Volume (MTV)
timeFrame: 4 weeks
Secondary outcomes:
measure: Weekly Global Symptom Assessment
timeFrame: 4 weeks
measure: Mean Daily Symptom Score in Functional Dyspepsia
timeFrame: 4 weeks
measure: Mean Daily Epigastric Pain in Functional Dyspepsia
timeFrame: 4 weeks
measure: Quality of Life in Functional Dyspepsia
timeFrame: 4 weeks
measure: Aggregate Symptom Score
timeFrame: 4 weeks
measure: Overall Severity in Gastroparesis
timeFrame: 4 weeks
measure: Average Daily Vomiting Episodes in Gastroparesis
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Michael Camilleri, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.