Pharmacodynamics, Pharmacogenetics, Clinical Efficacy and Safety of Cannabidiol for Gastroparesis and Functional Dyspepsia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 92
- 试验地点
- 1
- 主要终点
- Gastric Accommodation
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Cannabidiol (Drug)
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.
干预措施: placebo (Other)
结局指标
主要结局
Gastric Accommodation
时间窗: 4 weeks
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).
Satiation Maximum Tolerated Volume (MTV)
时间窗: 4 weeks
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.
Gastric Emptying Half-time (T1/2) of Solids
时间窗: 4 weeks
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.
Gastric Emptying Lag Time (T-lag) of Solids
时间窗: 4 weeks
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.
Fasting Gastric Volume
时间窗: 4 weeks
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).
Satiation Volume to Fullness
时间窗: 4 weeks
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.
次要结局
- Weekly Global Symptom Assessment(4 weeks)
- Mean Daily Symptom Score in Functional Dyspepsia(4 weeks)
- Mean Daily Epigastric Pain in Functional Dyspepsia(4 weeks)
- Quality of Life in Functional Dyspepsia(4 weeks)
- Aggregate Symptom Score(4 weeks)
- Overall Severity in Gastroparesis(4 weeks)
- Average Daily Vomiting Episodes in Gastroparesis(4 weeks)
研究者
Michael Camilleri, MD
Principal Investigator
Mayo Clinic