The Effects of Cannabinoid on Patients With Non-GERD Related Non Cardiac Chest Pain

Background: Noncardiac chest pain (NCCP) affects 200,000 new cases annually in USA. It is associated with poor quality of life and high health care expenditure of 8 Billion Dollars a year.

Gastroesophageal Reflux Disease(GERD), esophageal motility disorders, and psychological issues may cause NCCP.

The mechanism(s) for pain continue to be explored and include central and peripheral hypersensitivity, and mechanophysical abnormalities. Treatment of NCCP has focused on relieving visceral hypersensitivity through pain modulators, such as tricyclics, trazodone, or adenosine receptor antagonist, theophylline. Typically, only 40-50 % respond and clearly there is a large unmet therapeutic need.

Cannabis is felt to be beneficial for vomiting, diarrhea and intestinal pain. The main component of Cannabis acts through specific receptors, that are located primarily on central and peripheral neurons (including the enteric nervous system) and myenteric plexus where they modulate neurotransmitter release. Activation of these receptors reduces excitatory enteric transmission and may improve esophageal hyperreactivity and hypersensitivity, the hallmarks of NCCP.

STUDY PROTOCOL: The investigators will randomize 40 subjects with non-cardiac, non-reflux chest pain to receive dronabinol (5 mg Bid), or placebo for 4 weeks. Chest pain symptoms and esophageal sensorimotor properties will be assessed at baseline and at 4 weeks using symptom diary and impedance planimetry. The primary outcome measure will be the frequency of chest pain episodes. Secondary outcome measures include improvement in esophageal sensory thresholds, reduced reactive contractions, frequency, amplitude, area under the curve, and global improvement of symptoms.

HYPOTHESIS: Cannabinoids decrease esophageal hypersensitivity and ameliorate chest pain in NCCP patients, when compared to placebo.

AIM: To perform a randomized double blind study to investigate the effects of Dronabinol, a CB1 and CB2 agonist, in the treatment of patients with NCCP and examine its mechanism of action.

Study Overview

• Status: Completed
• Conditions: Chest Pain
• Intervention / Treatment: Drug: Marinol; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics

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:

• Male or Female
• Ages 18-75 years
• Non-GERD related Non cardiac chest pain (Evaluated previously with an EGD, Esophageal manometry, and 24 Hour ambulatory pH study)
• At least one episode of chest pain a week in the past month
• Previous negative cardiac evaluation (EKG ± Non invasive stress test ± Coronary angiogram)

Exclusion Criteria:

• Subjects requiring narcotics or other pain medications
• Subjects with known esophagitis, Barrett's esophagus or peptic stricture on endoscopy
• Subjects with previous upper gastrointestinal surgery
• Pregnancy
• Subjects with Diabetes, neuromuscular disorders, or other severe co-morbidities (Cardiovascular, respiratory, renal, hepatic, hematologic, endocrine, neurologic, and psychiatric)
• Subjects with upper airway symptoms (such as hoarseness, wheezing or laryngospasm)
• Medications such as baclofen, H2 blockers, PPI, sucralfate and prokinetics.
• Known history of substance abuse
• Nursing mothers

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
Placebo Comparator: Placebo	Drug: Placebo; 5mg BID, orally for 1 month
Experimental: Marinol	Drug: Marinol; 5mg BID, orally for 1 month

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of Chest Pain Episodes	Number of people still experiencing the same amount of chest pain during treatment than previously without	Baseline and 1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of Chest Pain in Treatment Group vs Baseline	Total (intensity (0(none) - 3(severe) + duration (0(none) - 3(longer than 30 mins)) at end of 1 month treatment; higher represents worse outcome; the total score ranges from 0 to 6 and is the sum of the intensity and duration	1 month
Intensity of Chest Pain Episodes	Intensity (0(none) - 3(severe)) at baseline vs 1 month for chest pain episodes; higher represents worse outcome; multiple chest pain totals are averaged	Baseline and 1 month
Sensory Thresholds for First Sensation	This is determined by the Esophageal Balloon Distension Test; range 0-65 mmHg	Baseline and 1 month
Duration of Chest Pain Episodes	0 - is none and 3 is longer than 30 mins; higher values is worst outcome; chest pain totals are averaged	Baseline vs 1 month
Sensory Thresholds for Discomfort	When participants felt pain at earliest pressure; range 0-65 mmHg	Baseline and 1 month
Sensory Thresholds for Pain	When highest amount of pain was felt; range is 0-65 mmHg	Baseline and 1 month

Collaborators and Investigators

• Sponsor: Yehudith Assouline-Dayan

Publications and helpful links

General Publications

• Reichenbach ZW, Sloan J, Rizvi-Toner A, Bayman L, Valestin J, Schey R. A 4-week pilot study with the cannabinoid receptor agonist dronabinol and its effect on metabolic parameters in a randomized trial. Clin Ther. 2015 Oct 1;37(10):2267-74. doi: 10.1016/j.clinthera.2015.07.023. Epub 2015 Aug 14.

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: May 10, 2012
• First Submitted That Met QC Criteria: May 14, 2012
• First Posted (Estimate): May 15, 2012

Study Record Updates

• Last Update Posted (Actual): April 28, 2017
• Last Update Submitted That Met QC Criteria: April 26, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Chest Pain; 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: 201003768