Chest Pain
Conditions
Brief summary
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.
Interventions
DRUGMarinol
5mg BID, orally for 1 month
DRUGPlacebo
5mg BID, orally for 1 month
Sponsors
Yehudith Assouline-Dayan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Chest Pain Episodes | Baseline and 1 month | Number of people still experiencing the same amount of chest pain during treatment than previously without |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Intensity of Chest Pain Episodes | Baseline and 1 month | Intensity (0(none) - 3(severe)) at baseline vs 1 month for chest pain episodes; higher represents worse outcome; multiple chest pain totals are averaged |
| Sensory Thresholds for First Sensation | Baseline and 1 month | This is determined by the Esophageal Balloon Distension Test; range 0-65 mmHg |
| Frequency of Chest Pain in Treatment Group vs Baseline | 1 month | 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 |
| Sensory Thresholds for Discomfort | Baseline and 1 month | When participants felt pain at earliest pressure; range 0-65 mmHg |
| Sensory Thresholds for Pain | Baseline and 1 month | When highest amount of pain was felt; range is 0-65 mmHg |
| Duration of Chest Pain Episodes | Baseline vs 1 month | 0 - is none and 3 is longer than 30 mins; higher values is worst outcome; chest pain totals are averaged |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Marinol Marinol: 5mg BID, orally for 1 month | 7 |
| Placebo Placebo: 5mg BID, orally for 1 month | 6 |
| Total | 13 |
Baseline characteristics
| Characteristic | Marinol | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 6 Participants | 13 Participants |
| Region of Enrollment United States | 7 participants | 6 participants | 13 participants |
| Sex: Female, Male Female | 6 Participants | 4 Participants | 10 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 7 | 1 / 6 |
| serious Total, serious adverse events | 0 / 7 | 0 / 6 |
Outcome results
Primary
Frequency of Chest Pain Episodes
Number of people still experiencing the same amount of chest pain during treatment than previously without
Time frame: Baseline and 1 month
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Marinol | Frequency of Chest Pain Episodes | 1 participants |
| Placebo | Frequency of Chest Pain Episodes | 3 participants |
Secondary
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
Time frame: Baseline vs 1 month
Population: 1 participant in placebo did not have this information completed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Marinol | Duration of Chest Pain Episodes | Baseline | 1.83 units on a scale | Standard Deviation 1.17 |
| Marinol | Duration of Chest Pain Episodes | 1 Month | 1.2 units on a scale | Standard Deviation 1.64 |
| Placebo | Duration of Chest Pain Episodes | Baseline | 1 units on a scale | Standard Deviation 1.55 |
| Placebo | Duration of Chest Pain Episodes | 1 Month | 1 units on a scale | Standard Deviation 1 |
Secondary
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
Time frame: 1 month
Population: 1 participant in placebo did not have this information completed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Marinol | Frequency of Chest Pain in Treatment Group vs Baseline | 1.87 units on a scale | Standard Deviation 2.58 |
| Placebo | Frequency of Chest Pain in Treatment Group vs Baseline | 1.8 units on a scale | Standard Deviation 1.64 |
Secondary
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
Time frame: Baseline and 1 month
Population: 1 participant in placebo did not have this information completed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Marinol | Intensity of Chest Pain Episodes | Baseline | 1.33 units on a scale | Standard Deviation 0.82 |
| Marinol | Intensity of Chest Pain Episodes | 1 Month | 0.67 units on a scale | Standard Deviation 1.03 |
| Placebo | Intensity of Chest Pain Episodes | Baseline | 0.6 units on a scale | Standard Deviation 0.89 |
| Placebo | Intensity of Chest Pain Episodes | 1 Month | 0.8 units on a scale | Standard Deviation 0.84 |
Secondary
Sensory Thresholds for Discomfort
When participants felt pain at earliest pressure; range 0-65 mmHg
Time frame: Baseline and 1 month
Population: 1 participant in marinol and 1 participant in placebo did not have this information completed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Marinol | Sensory Thresholds for Discomfort | Baseline | 6 mmHg | Standard Deviation 5.48 |
| Marinol | Sensory Thresholds for Discomfort | 1 Month | 8 mmHg | Standard Deviation 13.04 |
| Placebo | Sensory Thresholds for Discomfort | Baseline | 5 mmHg | Standard Deviation 5 |
| Placebo | Sensory Thresholds for Discomfort | 1 Month | 2 mmHg | Standard Deviation 4.47 |
Secondary
Sensory Thresholds for First Sensation
This is determined by the Esophageal Balloon Distension Test; range 0-65 mmHg
Time frame: Baseline and 1 month
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Marinol | Sensory Thresholds for First Sensation | 2 mmHg | Standard Deviation 0.125 |
| Placebo | Sensory Thresholds for First Sensation | 2.7 mmHg | Standard Deviation 0.103 |
Secondary
Sensory Thresholds for Pain
When highest amount of pain was felt; range is 0-65 mmHg
Time frame: Baseline and 1 month
Population: 1 participant in marinol and 1 participant in placebo did not have this information completed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Marinol | Sensory Thresholds for Pain | Baseline | 42 mmHg | Standard Deviation 16.81 |
| Marinol | Sensory Thresholds for Pain | 1 Month | 47 mmHg | Standard Deviation 16.8 |
| Placebo | Sensory Thresholds for Pain | Baseline | 53 mmHg | Standard Deviation 9.75 |
| Placebo | Sensory Thresholds for Pain | 1 Month | 51 mmHg | Standard Deviation 15.17 |