Effect of Cannabinoid Agonist on Gastrointestinal and Colonic Motor Functions in Patients With Irritable Bowel Syndrome (IBS)

NCT01253408 | Completed Phase 2 Results

• 3 other identifiers: 08-008314 Part AR01DK079866UL1RR024150
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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). Dronabinol is a synthetic medication (a medication made in a laboratory) related to the active ingredient of "cannabinoid or marijuana". Dronabinol is approved by the Food and Drug Administration (FDA) for preventing nausea and vomiting in patients with cancers undergoing chemotherapy. It is also used in AIDS patients with excessive weight loss for improvement in appetite and weight gain. The hypothesis in this study is that dronabinol will slow down the movement of food through the colon, and that this effect is regulated by the genes controlling the body messengers (receptors) that respond to medicinal marijuana or synthetic medicines that work on the same messengers that are present in the gastrointestinal tract and pain nerves.

Conditions

Irritable Bowel Syndrome

Keywords

anandamide; cannabinoid; fatty acid amide hydrolase; gastric; motility; small bowel

Outcome Measures

Primary Outcomes (1)

• Colonic Transit Geometric Center at 24 Hours

  The scintigraphic method is used to measure colonic transit. An isotope is adsorbed on activated charcoal particles and delivered to the colon in a delayed release capsule. Anterior and posterior gamma images are taken hourly. The geometric center (GC) is the weighted average of counts in the different colonic regions. The scale ranges from 1 to 5; a high GC implies faster colonic transit, a GC of 1 implies all isotope is in the ascending colon, and a GC of 5 implies all isotope is in the stool.

  24 hours

Secondary Outcomes (5)

• Colonic Transit Geometric Center

  28, 32, and 48 hours

• Gastric Emptying Half-Time (t1/2)

  Approximately 2 hours after radiolabel meal is ingested

• Colonic Filling at 6 Hours

  6 hours after radiolabeled meal was ingested

• Ascending Colon Emptying T 1/2

  48 hours after radiolabeled meal was ingested

• Gastric Emptying at 2 and 4 Hours

  2, 4 hours

Study Arms (3)

Dronabinol 2.5 mg bid

EXPERIMENTAL

Dronabinol 2.5 mg will be taken orally with water twice per day for two days.

Drug: Dronabinol

Dronabinol 5 mg bid

EXPERIMENTAL

Dronabinol 5 mg will be taken orally with water twice per day for two days.

Drug: Dronabinol

Placebo

PLACEBO COMPARATOR

Placebo will be taken orally with water twice per day for two days.

Drug: Placebo

Interventions

Dronabinol DRUG

Dronabinol is a synthetic delta-9-tetrahydrocannabinol, a nonselective cannabinoid agonist. Subjects will receive either 2.5 mg bid, or 5 mg bid, taken orally with water for 2 days.

Also known as: Marinol

Dronabinol 2.5 mg bid; Dronabinol 5 mg bid

Placebo DRUG

Placebo will match study drug; taken orally with water twice per day for two days.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-75 years
• Positive for IBS symptoms by Rome III criteria
• No prior abdominal surgery (except appendectomy or cholecystectomy)
• Baseline Geometric Center at 24 hours is greater/equal to 2.0
• Baseline Geometric Center at 48 hours is greater/equal to 3.9

You may not qualify if:

• Patients with significant depression (score of greater than 10 on Hospital and Anxiety Inventory)
• Patients with anxiety (score of greater than 10 on Hospital and Anxiety Inventory) will not be allowed to participate. However, patients on stable doses of selective serotonin re-uptake inhibitors (SSRIs) or low dose of tricyclic antidepressants will be eligible.

Sponsors & Collaborators

• Mayo Clinic: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• National Center for Research Resources (NCRR): collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Publications (2)

• 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.

  PMID: 21803011 BACKGROUND

• 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.

  PMID: 22288893 RESULT

MeSH Terms

Conditions

Irritable Bowel Syndrome

Interventions

Dronabinol

Condition Hierarchy (Ancestors)

Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Limitations and Caveats

This study included assessment of only four doses of dronabinol over 2 days.

Results Point of Contact

• Title: Dr. Michael Camilleri
• Organization: Mayo Clinic

camilleri.michael@mayo.edu

507-266-2306

Study Officials

• Michael Camilleri, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: November 18, 2010
• First Posted: December 3, 2010
• Study Start: September 1, 2009
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: May 7, 2013
• Results First Posted: May 7, 2013

Record last verified: 2013-03

Locations

US (1)