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

• Sponsor: Yehudith Assouline-Dayan (Other)
• Overall Status: Completed
• CT.gov ID: NCT01598207
• Collaborator: (none)
• Enrollment: 13
• Location: 1
• Arms: 2
• Duration (Months): 38.9
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chest Pain	Drug: Marinol; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 13 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Study Start Date: Feb 1, 2011
• Actual Primary Completion Date: May 1, 2014
• Actual Study Completion Date: May 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Marinol	Drug: Marinol; 5mg BID, orally for 1 month
Placebo Comparator: Placebo	Drug: Placebo; 5mg BID, orally for 1 month

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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

2. 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

3. Sensory Thresholds for First Sensation [Baseline and 1 month]

   This is determined by the Esophageal Balloon Distension Test; range 0-65 mmHg

4. 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

5. Sensory Thresholds for Discomfort [Baseline and 1 month]

   When participants felt pain at earliest pressure; range 0-65 mmHg

6. Sensory Thresholds for Pain [Baseline and 1 month]

   When highest amount of pain was felt; range is 0-65 mmHg

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242

Sponsors and Collaborators

• Yehudith Assouline-Dayan

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Yehudith Assouline-Dayan, Clinical Assistant Professor, University of Iowa
• ClinicalTrials.gov Identifier: NCT01598207
• Other Study ID Numbers: 201003768
• First Posted: May 15, 2012
• Last Update Posted: Apr 28, 2017
• Last Verified: Apr 1, 2017

• Additional relevant MeSH terms: Chest Pain; Dronabinol

Study Results

Participant Flow

Arm/Group Title	Marinol	Placebo
Arm/Group Description	Marinol: 5mg BID, orally for 1 month	Placebo: 5mg BID, orally for 1 month
Period Title: Overall Study
STARTED	7	6
COMPLETED	6	6
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Marinol	Placebo	Total
Arm/Group Description	Marinol: 5mg BID, orally for 1 month	Placebo: 5mg BID, orally for 1 month	Total of all reporting groups
Overall Participants	7	6	13
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	7 100%	6 100%	13 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	6 85.7%	4 66.7%	10 76.9%
Male	1 14.3%	2 33.3%	3 23.1%
Region of Enrollment (participants) [Number]
United States	7 100%	6 100%	13 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Marinol	Placebo
Arm/Group Description	Marinol: 5mg BID, orally for 1 month	Placebo: 5mg BID, orally for 1 month
Measure Participants	6	6
Number [participants]	1 14.3%	3 50%

2. Secondary Outcome

Title	Frequency of Chest Pain in Treatment Group vs Baseline
Description	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

Outcome Measure Data

Analysis Population Description

1 participant in placebo did not have this information completed

Arm/Group Title	Marinol	Placebo
Arm/Group Description	Marinol: 5mg BID, orally for 1 month	Placebo: 5mg BID, orally for 1 month
Measure Participants	6	5
Mean (Standard Deviation) [units on a scale]	1.87 (2.58)	1.8 (1.64)

3. Secondary Outcome

Title	Intensity of Chest Pain Episodes
Description	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

Outcome Measure Data

Analysis Population Description

1 participant in placebo did not have this information completed

Arm/Group Title	Marinol	Placebo
Arm/Group Description	Marinol: 5mg BID, orally for 1 month	Placebo: 5mg BID, orally for 1 month
Measure Participants	6	5
Baseline	1.33 (0.82)	0.6 (0.89)
1 Month	0.67 (1.03)	0.8 (0.84)

4. Secondary Outcome

Title	Sensory Thresholds for First Sensation
Description	This is determined by the Esophageal Balloon Distension Test; range 0-65 mmHg
Time Frame	Baseline and 1 month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Marinol	Placebo
Arm/Group Description	Marinol: 5mg BID, orally for 1 month	Placebo: 5mg BID, orally for 1 month
Measure Participants	6	6
Mean (Standard Deviation) [mmHg]	2 (.125)	2.7 (.103)

5. Secondary Outcome

Title	Duration of Chest Pain Episodes
Description	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

Outcome Measure Data

Analysis Population Description

1 participant in placebo did not have this information completed

Arm/Group Title	Marinol	Placebo
Arm/Group Description	Marinol: 5mg BID, orally for 1 month	Placebo: 5mg BID, orally for 1 month
Measure Participants	6	5
Baseline	1.83 (1.17)	1 (1.55)
1 Month	1.2 (1.64)	1 (1)

6. Secondary Outcome

Title	Sensory Thresholds for Discomfort
Description	When participants felt pain at earliest pressure; range 0-65 mmHg
Time Frame	Baseline and 1 month

Outcome Measure Data

Analysis Population Description

1 participant in marinol and 1 participant in placebo did not have this information completed

Arm/Group Title	Marinol	Placebo
Arm/Group Description	Marinol: 5mg BID, orally for 1 month	Placebo: 5mg BID, orally for 1 month
Measure Participants	5	5
Baseline	6 (5.48)	5 (5)
1 Month	8 (13.04)	2 (4.47)

7. Secondary Outcome

Title	Sensory Thresholds for Pain
Description	When highest amount of pain was felt; range is 0-65 mmHg
Time Frame	Baseline and 1 month

Outcome Measure Data

Analysis Population Description

1 participant in marinol and 1 participant in placebo did not have this information completed

Arm/Group Title	Marinol	Placebo
Arm/Group Description	Marinol: 5mg BID, orally for 1 month	Placebo: 5mg BID, orally for 1 month
Measure Participants	5	5
Baseline	42 (16.81)	53 (9.75)
1 Month	47 (16.8)	51 (15.17)

Adverse Events

Arm/Group Title	Marinol		Placebo
Arm/Group Description	Marinol: 5mg BID, orally for 1 month		Placebo: 5mg BID, orally for 1 month
All Cause Mortality
	Marinol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Marinol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Marinol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/7 (14.3%)		1/6 (16.7%)
Gastrointestinal disorders
Viral Gastroenteritis	1/7 (14.3%)	1	1/6 (16.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.