Effect of a Cannabinoid Agonist on Colonic Sensory Functions in Patients With Irritable Bowel Syndrome

M

Michael Camilleri

Status and phase

Completed
Phase 2

Conditions

Irritable Bowel Syndrome

Treatments

Drug: Dronabinol
Drug: Placebo

Study type

Interventional

Funder types

Other
NIH

Identifiers

NCT01786109
UL1RR024150 (U.S. NIH Grant/Contract)
08-008314 Part B
R01DK079866 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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).

Full 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: 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". Bowel preparation with PEG and electrolyte-containing oral colonic lavage solution, followed by a 12 hour fast. 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. 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.

Enrollment

75 patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

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.

Trial design

75 participants in 3 patient groups, including a placebo group

Dronabinol 2.5 mg
Experimental group
Description:
One dose of dronabinol 2.5 mg was taken orally with water.
Treatment:
Drug: Dronabinol
Dronabinol 5 mg
Experimental group
Description:
One dose of dronabinol 5 mg was taken orally with water.
Treatment:
Drug: Dronabinol
Placebo
Placebo Comparator group
Description:
One dose of placebo was taken orally with water.
Treatment:
Drug: Placebo

Trial contacts and locations

1

Loading...

Data sourced from clinicaltrials.gov

Clinical trials

Find clinical trialsTrials by location
© Copyright 2024 Veeva Systems