Esophageal Diseases
Conditions
Keywords
Functional Chest Pain, Non-Cardiac Chest Pain, Esophageal Hypersensitivity
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.
Interventions
DRUGDronabinol
Dronabinol 5 mg, every other night, orally
DRUGPlacebo
Placebo--no drug
Sponsors
Temple University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Chest Pain | Daily assessment for 12 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| GERD Symptom Checklist | Baseline, 2, 4, 8, and 12 weeks | Patients will fill out a questionnaire pertaining to GERD symptoms which will be normalized to a numerical value for comparison among groups. |
| Short Form 36 | Baseline, 2, 4, 8, and 12 weeks | 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 |
| Esophageal Hypersensitivity and Distention | Baseline, 4, 8, and 12 weeks | Sensory thresholds for first sensation, discomfort, and pain in the esophagus. Frequency, amplitude, area under the curve (AUC) of reactive esophageal contractions |
| Beck Depression Index | Baseline, 2, 4, 8, and 12 weeks | Analysis of depressive symptoms normalized to a numerical value for comparison among groups. |
| Metabolic Parameters | Baseline, 2, 4, 8, and 12 weeks | Total cholesterol will be measured and reported in mg/dL. |
| Weight | Baseline, 2, 4, 8, and 12 weeks | Patient mass will be measured in kg. |
| Beck Anxiety Index | Baseline, 2, 4, 8, and 12 weeks | Analysis of anxious symptoms normalized to a numerical value for comparison among groups. |
| Waist Circumference | Baseline, 2, 4, 8, and 12 weeks | Patient's waist in cm will be measured. |
| Non-HDL Cholesterol | Baseline, 2, 4, 8, and 12 weeks | Non-HDL cholesterol will be measured and reported in mg/dL. |
| Chest Pain Intensity | Daily assessment for 12 weeks | 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. |
| Triglycerides | Baseline, 2, 4, 8, and 12 weeks | Triglycerides will be measured and reported in mg/dL. |
| Glucose | Baseline, 2, 4, 8, and 12 weeks | Glucose will be measured and reported in mg/dL. |
| Insulin | Baseline, 2, 4, 8, and 12 weeks | Insulin will be measured and reported in µU/mL. |
| Leptin | Baseline, 2, 4, 8, and 12 weeks | Leptin will be measured and reported in ng/mL. |
| ALT | Baseline, 2, 4, 8, and 12 weeks | Leptin will be measured and reported in IU/L. |
| AST | Baseline, 2, 4, 8, and 12 weeks | Leptin will be measured and reported in IU/L. |
| LDH | Baseline, 2, 4, 8, and 12 weeks | LDH will be measured and reported in IU/L. |
| CRP | Baseline, 2, 4, 8, and 12 weeks | CRP will be measured and reported in mg/L. |
| HDL Cholesterol | Baseline, 2, 4, 8, and 12 weeks | HDL cholesterol will be measured and reported in mg/dL. |
Countries
United States
Outcome results
None listed