Clinical trial NCT02569073: Investigation of Cannabinoid Receptor Agonist Dronabinol in Patients With Functional Chest Pain
Official title: Investigation of Cannabinoid Receptor Agonist Dronabinol in Patients With Functional Chest Pain
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Esophageal Diseases
Keywords: Functional Chest Pain
Non-Cardiac Chest Pain
Esophageal Hypersensitivity
Lead sponsor: Temple University
Sponsor class: OTHER
First posted: 2015-10-06
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Chest Pain
timeFrame: Daily assessment for 12 weeks
Secondary outcomes:
measure: Chest Pain Intensity
timeFrame: Daily assessment for 12 weeks
measure: GERD Symptom Checklist
timeFrame: Baseline, 2, 4, 8, and 12 weeks
measure: Short Form 36
timeFrame: Baseline, 2, 4, 8, and 12 weeks
measure: Esophageal Hypersensitivity and Distention
timeFrame: Baseline, 4, 8, and 12 weeks
measure: Beck Depression Index
timeFrame: Baseline, 2, 4, 8, and 12 weeks
measure: Metabolic Parameters
timeFrame: Baseline, 2, 4, 8, and 12 weeks
measure: Weight
timeFrame: Baseline, 2, 4, 8, and 12 weeks
measure: Beck Anxiety Index
timeFrame: Baseline, 2, 4, 8, and 12 weeks
measure: Waist Circumference
timeFrame: Baseline, 2, 4, 8, and 12 weeks
measure: Non-HDL Cholesterol
timeFrame: Baseline, 2, 4, 8, and 12 weeks
measure: HDL Cholesterol
timeFrame: Baseline, 2, 4, 8, and 12 weeks
measure: Triglycerides
timeFrame: Baseline, 2, 4, 8, and 12 weeks
measure: Glucose
timeFrame: Baseline, 2, 4, 8, and 12 weeks
measure: Insulin
timeFrame: Baseline, 2, 4, 8, and 12 weeks
measure: Leptin
timeFrame: Baseline, 2, 4, 8, and 12 weeks
measure: ALT
timeFrame: Baseline, 2, 4, 8, and 12 weeks
measure: AST
timeFrame: Baseline, 2, 4, 8, and 12 weeks
measure: LDH
timeFrame: Baseline, 2, 4, 8, and 12 weeks
measure: CRP
timeFrame: Baseline, 2, 4, 8, and 12 weeks
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
Study officials:
affiliation: Temple University
name: Ron W Schey, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Temple University
name: Zachary W Reichenbach, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Temple University
name: Henry Parkman, M.D.
role: PRINCIPAL_INVESTIGATOR
References: