Investigation of Cannabinoid Receptor Agonist Dronabinol in Patients With Functional Chest Pain (ICAMP)

In a recent study, Dronabinol was shown to reduce symptoms in patients with Functional Chest Pain (non-cardiac chest pain). Additionally, metabolic measures and patients' weights were not adversely affected by this regiment. In fact, some cholesterol measures trended in a favorable direction with Dronabinol. The study lasted 28 days and patients took Dronabinol twice daily. The goal of this current study focuses on reducing the dose of Dronabinol to see if the same goals can be achieved. More so, the study will be extended to 12 weeks to gain a more longitudinal picture of therapy with Dronabinol. It is hypothesized that reducing the dose and extending the duration will continue to show an improvement in symptoms as well as no adverse metabolic outcomes.

Study Overview

• Status: Withdrawn
• Conditions: Esophageal Diseases
• Intervention / Treatment: Drug: Dronabinol; Drug: Placebo

Detailed Description

About 200,000 new cases of Functional Chest Pain (FCP) are diagnosed annually in USA. FCP is associated with poor quality of life and high health care expenditure. Gastroesophageal reflux disease (GERD), esophageal motility disorders, and psychological disorders may cause FCP. However, the mechanism(s) for FCP continue to be explored and include central and peripheral hypersensitivity as well as biomechanical dysfunction of the esophageal wall. CB1 receptor activation in synaptic clefts fine tunes neuronal firing and may in fact quell the over excitation associated with hypersensitivity.

Dronabinol, a cannabinoid receptor agonist with a preference for CB1 over CB2, is believed to reduce the esophageal hypersensitivity. CB1 receptors are located primarily on central and peripheral neurons (including the enteric nervous system) and myenteric plexus where they modulate neurotransmitter release. Activation of pre-junctional CB1 receptors may reduce excitatory enteric transmission and conceivably improve esophageal hyperreactivity and hypersensitivity, the hallmarks of FCP.

Previously, it was shown that Chest Pain Symptoms were greatly reduced when patients took 5 mg Dronabinol twice daily. Patients had very few side effects from this regiment although sedation was reported. The goal of this study focuses on reducing the dose of Dronabinol to 5 mg every other day, or essentially, one quarter of the dose. The effect of Dronabinol varies with CB1 receptor density in various tissues. It is hypothesized that at this reduced dose relief of chest pain will still be achieved without the sedating effects.

More so, Dronabinol at 5 mg twice daily failed to produce any adverse metabolic outcomes including measures of glucose, LDL, triglycerides, leptin, or transaminases. Dronabinol treatment tended to improve some of these measures although the study only lasted 28 days. Currently the hypothesis is that lower doses at a protracted time course will again fail to perturb homeostasis.

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

At least one episode of chest pain a week in the past month. Previous negative cardiac evaluation (EKG ± non invasive stress test ± coronary angiogram). Negative esophageal evaluation for a motility disorder (eg: achalasia) and GERD (normal endoscopy, normal 24 hr pH study, or unresponsive to 6 weeks of BID PPI therapy)

Exclusion Criteria:

1. Subjects requiring narcotics or other pain medications,
2. Subjects with known GERD (unless responsive to PPI therapy and on a stable dose), esophagitis, Barrett's esophagus or peptic stricture on endoscopy
3. Subjects with previous upper gastrointestinal surgery
4. Pregnancy
5. Subjects with diabetes, neuromuscular disorders, cardiac disorders, or other severe co-morbidities (Cardiovascular, respiratory, renal, hepatic, hematologic, endocrine, neurologic).
6. Subjects with upper airway symptoms (such as hoarseness, wheezing or laryngospasm)
7. Medications such as baclofen, sucralfate and prokinetic agents or any agent considered a sedative, hypnotic, or psychoactive drug.
8. Known history of substance abuse.
9. Subject unable to consent.
10. Patient has history of comorbid psychiatric conditions including mania and schizophrenia. Patients will also be excluded who currently have a diagnosis of depression or undergoing treatment for depression.

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
Experimental: Dronabinol; Patients who receive Dronabinol 5 mg, every other night, orally.	Drug: Dronabinol; Dronabinol 5 mg, every other night, orally; Other Names: Marinol
Placebo Comparator: Placebo; Patients who receive Placebo every other night, orally	Drug: Placebo; Placebo--no drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chest Pain	Patient will fill out a Chest Pain Questionnaire and symptom diary daily of symptoms which will be normalized to a numerical value for comparison among groups.	Daily assessment for 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chest Pain Intensity	Patient will fill out a Chest Pain Questionnaire and symptom diary daily of symptoms which will be normalized to a numerical value for comparison among groups.	Daily assessment for 12 weeks
GERD Symptom Checklist	Patients will fill out a questionnaire pertaining to GERD symptoms which will be normalized to a numerical value for comparison among groups.	Baseline, 2, 4, 8, and 12 weeks
Short Form 36	A general health-related quality of life questionnaire that examines 8 domains: Physical Functioning, Role Functioning Physical, Role Functioning Emotional, Mental Health, Vitality, Bodily Pain, General Health, and Social Functioning	Baseline, 2, 4, 8, and 12 weeks
Esophageal Hypersensitivity and Distention	Sensory thresholds for first sensation, discomfort, and pain in the esophagus. Frequency, amplitude, area under the curve (AUC) of reactive esophageal contractions	Baseline, 4, 8, and 12 weeks
Beck Depression Index	Analysis of depressive symptoms normalized to a numerical value for comparison among groups.	Baseline, 2, 4, 8, and 12 weeks
Metabolic Parameters	Total cholesterol will be measured and reported in mg/dL.	Baseline, 2, 4, 8, and 12 weeks
Weight	Patient mass will be measured in kg.	Baseline, 2, 4, 8, and 12 weeks
Beck Anxiety Index	Analysis of anxious symptoms normalized to a numerical value for comparison among groups.	Baseline, 2, 4, 8, and 12 weeks
Waist Circumference	Patient's waist in cm will be measured.	Baseline, 2, 4, 8, and 12 weeks
Non-HDL Cholesterol	Non-HDL cholesterol will be measured and reported in mg/dL.	Baseline, 2, 4, 8, and 12 weeks
HDL Cholesterol	HDL cholesterol will be measured and reported in mg/dL.	Baseline, 2, 4, 8, and 12 weeks
Triglycerides	Triglycerides will be measured and reported in mg/dL.	Baseline, 2, 4, 8, and 12 weeks
Glucose	Glucose will be measured and reported in mg/dL.	Baseline, 2, 4, 8, and 12 weeks
Insulin	Insulin will be measured and reported in µU/mL.	Baseline, 2, 4, 8, and 12 weeks
Leptin	Leptin will be measured and reported in ng/mL.	Baseline, 2, 4, 8, and 12 weeks
ALT	Leptin will be measured and reported in IU/L.	Baseline, 2, 4, 8, and 12 weeks
AST	Leptin will be measured and reported in IU/L.	Baseline, 2, 4, 8, and 12 weeks
LDH	LDH will be measured and reported in IU/L.	Baseline, 2, 4, 8, and 12 weeks
CRP	CRP will be measured and reported in mg/L.	Baseline, 2, 4, 8, and 12 weeks

Collaborators and Investigators

• Sponsor: Temple University
• Investigators: Principal Investigator: Ron W Schey, M.D., Temple University; Principal Investigator: Zachary W Reichenbach, M.D., Ph.D., Temple University; Principal Investigator: Henry Parkman, M.D., Temple University

Study record dates

Study Major Dates

• Study Start (Actual): June 21, 2017
• Primary Completion (Actual): August 1, 2019
• Study Completion (Actual): September 1, 2019

Study Registration Dates

• First Submitted: September 30, 2015
• First Submitted That Met QC Criteria: October 5, 2015
• First Posted (Estimate): October 6, 2015

Study Record Updates

• Last Update Posted (Actual): September 26, 2019
• Last Update Submitted That Met QC Criteria: September 25, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Functional Chest Pain; Non-Cardiac Chest Pain; Esophageal Hypersensitivity
• Additional Relevant MeSH Terms: Digestive System Diseases; Pain; Neurologic Manifestations; Gastrointestinal Diseases; Chest Pain; Esophageal Diseases; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Psychotropic Drugs; Hallucinogens; Cannabinoid Receptor Agonists; Cannabinoid Receptor Modulators; Dronabinol
• Other Study ID Numbers: 22894

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