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Efficacy and Safety of Cannabidiol for Gastroparesis and Functional Dyspepsia

Primary Purpose

Gastroparesis, Dyspepsia

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Cannabidiol
placebo
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastroparesis

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Mayo Clinic in Rochester

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Pharmacodynamics and clinical effects of cannabidiol

pharmacodynamics and clinical effects of placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Primary endpoint gastric accommodation
Fasting gastric and accommodation volumes (mL) measured by SPECT
Primary Endpoint satiation
Volume to fullness (VTF, mL) on satiation test
Primary endpoint Gastric emptying
Gastric emptying T1/2 of solids on scintigraphy, minutes
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
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

Secondary Outcome Measures

Secondary Endpoint Gastric emptying
Gastric emptying of solids at 2 hours and 4 hours on scintigraphy, %
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
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
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
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"
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"
Secondary Endpoint: Adequate relief response in functional dyspepsia
Single question on adequate relief answered "yes" or "no"
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

Full Information

First Posted
May 3, 2019
Last Updated
April 3, 2023
Sponsor
Mayo Clinic
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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1. Study Identification

Unique Protocol Identification Number
NCT03941288
Brief Title
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

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
September 4, 2019 (Actual)
Primary Completion Date
February 23, 2023 (Actual)
Study Completion Date
February 23, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mayo Clinic
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastroparesis, Dyspepsia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
111 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Pharmacodynamics and clinical effects of cannabidiol
Arm Type
Active Comparator
Arm Description
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.
Arm Title
pharmacodynamics and clinical effects of placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Cannabidiol
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
Primary endpoint gastric accommodation
Description
Fasting gastric and accommodation volumes (mL) measured by SPECT
Time Frame
4 Weeks
Title
Primary Endpoint satiation
Description
Volume to fullness (VTF, mL) on satiation test
Time Frame
4 weeks
Title
Primary endpoint Gastric emptying
Description
Gastric emptying T1/2 of solids on scintigraphy, minutes
Time Frame
4 weeks
Title
Primary endpoint Gastroparesis symptoms
Description
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
Time Frame
Daily diary over 4 weeks
Title
Primary endpoint functional dyspepsia symptoms
Description
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
Time Frame
Every 2 weeks
Secondary Outcome Measure Information:
Title
Secondary Endpoint Gastric emptying
Description
Gastric emptying of solids at 2 hours and 4 hours on scintigraphy, %
Time Frame
4 Weeks
Title
Secondary Endpoint Symptom scores during gastric emptying test
Description
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
Time Frame
over 4 hours at 4 weeks
Title
Secondary Endpoint Satiation
Description
Maximum tolerated volume (mL) and aggregate symptoms (nausea, fullness, bloating, pain on 0-100mm visual analog scale), scored 30min after MTV on satiation
Time Frame
over 2 hour test at week 4
Title
Secondary Endpoint Gastroparesis symptoms
Description
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
Time Frame
4 weeks
Title
Secondary Endpoint: Overall dyspepsia score
Description
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"
Time Frame
Every 2 weeks
Title
Secondary Endpoint: Pain score in dyspepsia
Description
Pain based on Nepean Dyspepsia Index (NDI) score based on 5 point scale ranging from "not at all" to "extremely"
Time Frame
Every 2 weeks
Title
Secondary Endpoint: Adequate relief response in functional dyspepsia
Description
Single question on adequate relief answered "yes" or "no"
Time Frame
4 weeks
Title
Secondary endpoint: Daily score in functional dyspepsia
Description
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
Time Frame
daily for 4 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Camilleri, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35537858
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.
Results Reference
derived
Links:
URL
https://www.mayo.edu/research/clinical-trials
Description
Mayo Clinic Clinical Trials

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Efficacy and Safety of Cannabidiol for Gastroparesis and Functional Dyspepsia

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