Clinical trial NCT01786109: Effect of a Cannabinoid Agonist on Colonic Sensory Functions in Patients With Irritable Bowel Syndrome
Official title: Study on the Effect of Cannabinoid Agonist on Gastrointestinal and Colonic Motor and Sensory Functions in Patients With Diarrhea-Predominant Irritable Bowel Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Irritable Bowel Syndrome
Keywords: anandamide
cannabinoid
fatty acid amide hydrolase
gastric
motility
small bowel
sensory
motor
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: National Center for Research Resources (NCRR)
First posted: 2013-02-07
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL

Brief summary: Irritable bowel syndrome (IBS) affects about 15% of the U.S. population. There are still no effective and safe medications approved for the treatment of abdominal pain associated with bowel symptoms in IBS. This study will investigate the effects of an approved medication, Dronabinol, on the movement of food through the stomach and colon in subjects with a history of diarrhea-predominant Irritable Bowel Syndrome (D-IBS).

Detailed description: Irritable bowel syndrome (IBS) affects about 15% of the U.S. population. Despite increasing understanding of the pathophysiology of IBS, there is no effective medication approved for the treatment of abdominal pain associated with IBS. Cannabinoid receptors (CBR) are on cholinergic neurons in the brain stem, stomach and colon. A cannabinoid receptor 1 (CB1) antagonist, rimonabant, is effective in induction of weight loss; however, the mechanism of this benefit is unclear. Human studies from this lab show that a CBR agonist, dronabinol, inhibits gastric and colonic motility, which may alter appetite or satiation in obesity, and may have potential in the treatment of IBS. The overall focus of the study is on the mechanisms involved in the modulation of gastric and colonic motor and sensory functions by cannabinoid receptors (CBR) in health and in IBS. CB1 receptors are also involved in nociception and in mediating inflammation which are increasingly recognized as being potential pathophysiological mechanisms in IBS.

All participants underwent the following procedures:

1. Documentation of eligibility, screening questionnaires and physical examination, including exclusion of rectal evacuation disorder by standard clinical evaluation within the past 12 months; this was important to ensure the diarrhea was not secondary to "retention with overflow".
2. Bowel preparation with PEG and electrolyte-containing oral colonic lavage solution, followed by a 12 hour fast.
3. Colonic testing of compliance, tone, motility and sensation measurement. Colonic compliance, fasting tone, sensory thresholds and sensory ratings in response to random-order phasic distensions were performed before treatment was administered. Then medication was ingested, and after 60 minutes, the same studies were performed that is compliance, fasting tone, sensory thresholds and sensory ratings in response to random-order phasic distensions. Participants also filled in responses to questionnaires (using 100 mm VAS scales) to describe their sense of tiredness, peace, worry and activity at the time of the measurements of sensation. Finally, participants ingested a standard chocolate 1000 kcal milkshake meal, and postprandial colonic tone and motility were measured for one hour.
4. With appropriate consent, a venous blood sample was obtained from each participant for DNA extraction; this will be used in ongoing pharmacogenomics studies.

Note: This study is related to NCT01253408, part A of the same protocol. Part A explored the effect of dronabinol on gastric and colonic motor functions.

Eligibility criteria: Inclusion Criteria:

* Age 18-75 years
* Positive for IBS symptoms by Rome III criteria
* No prior abdominal surgery (except appendectomy or cholecystectomy
* Score of 10 or less on either Anxiety or Depression on the Hospital Anxiety/Depression Inventory

Exclusion Criteria:

* Patients with significant depression (score of greater than 10 on Hospital Depression Inventory
* Patients with anxiety (score of greater than 10 on Hospital Anxiety Inventory. However, patients on stable doses of selective serotonin inhibitors (SSRIs) or low dose of tricyclic antidepressants will be eligible.

Primary outcomes:
measure: Colonic Compliance at Pressure at Half-Maximum Volume (Pr 1/2)
timeFrame: 1 hour after drug was ingested
Secondary outcomes:
measure: Postprandial Change in Colonic Tone
timeFrame: 1 hour after ingestion of standard meal
measure: Post-treatment Sensory Threshold for First Perception of Pain
timeFrame: 1 hour after drug was ingested
measure: Post-Treatment Overall Sensory Rating in Response to 16, 24, 32, and 40 mm Hg Distensions
timeFrame: 1 hour after drug was ingested
measure: Fasting Colonic Tone
timeFrame: After 12 hour fast, before drug administered
measure: Postprandial Colonic Motility Index
timeFrame: 1 hour after ingestion of standard meal
measure: Post-treatment Sensory Threshold for First Sensation
timeFrame: 1 hour after drug was ingested
measure: Post-Treatment Sensory Threshold for First Perception of Gas
timeFrame: 1 hour after drug was ingested
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Michael Camilleri, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wong BS, Camilleri M, Eckert D, Carlson P, Ryks M, Burton D, Zinsmeister AR. Randomized pharmacodynamic and pharmacogenetic trial of dronabinol effects on colon transit in irritable bowel syndrome-diarrhea. Neurogastroenterol Motil. 2012 Apr;24(4):358-e169. doi: 10.1111/j.1365-2982.2011.01874.x. Epub 2012 Jan 30.
citation: Wong BS, Camilleri M, Busciglio I, Carlson P, Szarka LA, Burton D, Zinsmeister AR. Pharmacogenetic trial of a cannabinoid agonist shows reduced fasting colonic motility in patients with nonconstipated irritable bowel syndrome. Gastroenterology. 2011 Nov;141(5):1638-47.e1-7. doi: 10.1053/j.gastro.2011.07.036. Epub 2011 Jul 29.