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

Esophageal Diseases Clinical Trial

— ICAMP  

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02569073
• Other study ID #: 22894
• Status: Withdrawn
• Phase: Phase 4
• Start date: June 21, 2017
• Est. completion date: September 1, 2019

Study information

• Verified date: September 2019
• Source: Temple University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: September 1, 2019
• Est. primary completion date: August 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chest Pain
• Esophageal Diseases

Intervention

Drug:
• Dronabinol
Dronabinol 5 mg, every other night, orally
• Placebo
Placebo--no drug

Locations

Country	Name	City	State
United States	Temple University Hospital	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Temple University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Beck Depression Index	Analysis of depressive symptoms normalized to a numerical value for comparison among groups.	Baseline, 2, 4, 8, and 12 weeks
Secondary	Metabolic Parameters	Total cholesterol will be measured and reported in mg/dL.	Baseline, 2, 4, 8, and 12 weeks
Secondary	Weight	Patient mass will be measured in kg.	Baseline, 2, 4, 8, and 12 weeks
Secondary	Beck Anxiety Index	Analysis of anxious symptoms normalized to a numerical value for comparison among groups.	Baseline, 2, 4, 8, and 12 weeks
Secondary	Waist Circumference	Patient's waist in cm will be measured.	Baseline, 2, 4, 8, and 12 weeks
Secondary	Non-HDL Cholesterol	Non-HDL cholesterol will be measured and reported in mg/dL.	Baseline, 2, 4, 8, and 12 weeks
Secondary	HDL Cholesterol	HDL cholesterol will be measured and reported in mg/dL.	Baseline, 2, 4, 8, and 12 weeks
Secondary	Triglycerides	Triglycerides will be measured and reported in mg/dL.	Baseline, 2, 4, 8, and 12 weeks
Secondary	Glucose	Glucose will be measured and reported in mg/dL.	Baseline, 2, 4, 8, and 12 weeks
Secondary	Insulin	Insulin will be measured and reported in µU/mL.	Baseline, 2, 4, 8, and 12 weeks
Secondary	Leptin	Leptin will be measured and reported in ng/mL.	Baseline, 2, 4, 8, and 12 weeks
Secondary	ALT	Leptin will be measured and reported in IU/L.	Baseline, 2, 4, 8, and 12 weeks
Secondary	AST	Leptin will be measured and reported in IU/L.	Baseline, 2, 4, 8, and 12 weeks
Secondary	LDH	LDH will be measured and reported in IU/L.	Baseline, 2, 4, 8, and 12 weeks
Secondary	CRP	CRP will be measured and reported in mg/L.	Baseline, 2, 4, 8, and 12 weeks