Irritable Bowel SyndromePhase 2NCT01786109
Effect of a Cannabinoid Agonist on Colonic Sensory Functions in Patients With Irritable Bowel Syndrome
A Phase 2 study testing Dronabinol in people with Irritable Bowel Syndrome, run by Michael Camilleri at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Irritable Bowel Syndrome
- What is being tested?
- Dronabinol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 75 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2009to Dec 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
1 site in 1 country.
About this study
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
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).
Read the 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:
- 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.
- Conditions
- Irritable Bowel Syndrome
- Being tested
- Dronabinol, Placebo
- Keywords
- anandamide, cannabinoid, fatty acid amide hydrolase, gastric, motility, small bowel, sensory, motor
- Medical subject headings
- Irritable Bowel Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DronabinolDrug
Also called Marimol
Dronabinol is a synthetic delta-9-tetrahydrocannabinol, a nonselective cannabinoid agonist. Subjects received one dose of either 2.5 mg or 5 mg orally with water.
PlaceboDrug
Placebo will match study drug; taken as one dose orally with water.
| Study group | Role | What they receive |
|---|---|---|
| Dronabinol 2.5 mg | Experimental | One dose of dronabinol 2.5 mg was taken orally with water. Receives: Drug: Dronabinol |
| Dronabinol 5 mg | Experimental | One dose of dronabinol 5 mg was taken orally with water. Receives: Drug: Dronabinol |
| Placebo | Placebo comparator | One dose of placebo was taken orally with water. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Colonic Compliance at Pressure at Half-Maximum Volume (Pr 1/2)
Colonic compliance is a measure of the "stiffness" of the colon, that is, what pressure was needed to reach half the maximum volume of the colon.
After the barostat catheter was inserted in the colon, the catheter was connected to a barostat machine. After an initial conditioning distension to 20 mm Hg, colonic compliance was measured by step-wise inflation with increments of 4 mm Hg up to 64 mm Hg. Colonic compliance was analyzed by a validated linear interpolation method. The pressure at half maximum volume serves as a summary of colonic compliance.
Measured: 1 hour after drug was ingested
Secondary outcomes (7)
Postprandial Change in Colonic Tone
Colonic tone is a measurement of the volume of the colon. Colonic tone was assessed by noting the changes in the balloon volume in the presence of a constant operating pressure in the balloon (in the barostat-manometric assembly placed in the colon.)
Measured: 1 hour after ingestion of standard meal
Post-treatment Sensory Threshold for First Perception of Pain
The sensory threshold for first perception of pain was measured by stepwise inflation in increments of 4 mm Hg at 60 second intervals up to a maximum pressure of 64 mm Hg. During this assessment participants were asked to report when they had the first sensation. The investigator recorded the threshold pressure at which the participants reported this sensation.
Measured: 1 hour after drug was ingested
Post-Treatment Overall Sensory Rating in Response to 16, 24, 32, and 40 mm Hg Distensions
The sensory rating was measured by a 100 mm long Visual Analog Scale (VAS). The VAS does not have any pre-set marks between the extremes of 0 for no pain and 100 mm for extreme pain. The investigator measures the mark made by the participant in mm and records this for the value of pain.
Measured: 1 hour after drug was ingested
Fasting Colonic Tone
Colonic tone is a measurement of the volume of the colon. Colonic tone was assessed by noting the changes in the balloon volume in the presence of a constant operating pressure in the balloon (in the barostat-manometric assembly placed in the colon.)
Measured: After 12 hour fast, before drug administered
Postprandial Colonic Motility Index
Colonic phasic pressure activity is summarized as a motility index (MI)=log_e[number of contractions * sum of amplitudes) + 1]. A normal fasting average motility index (MI) would be about 12. An increase in MI means an increase in the phasic contractions (in contrast to tone) which is measured as a change in volume of the barostat balloon. (Therefore, an increase in MI means that the meal is moving more quickly through the colon.)
Measured: 1 hour after ingestion of standard meal
Post-treatment Sensory Threshold for First Sensation
The sensory threshold for first sensation was measured by stepwise inflation in increments of 4 mm Hg at 60 second intervals up to a maximum pressure of 64 mm Hg. During this assessment participants were asked to report when they had the first sensation. The investigator recorded the threshold pressure at which the participants reported this sensation.
Measured: 1 hour after drug was ingested
Post-Treatment Sensory Threshold for First Perception of Gas
The sensory threshold for first perception of gas was measured by stepwise inflation in increments of 4 mm Hg at 60 second intervals up to a maximum pressure of 64 mm Hg. During this assessment participants were asked to report when they had the first sensation. The investigator recorded the threshold pressure at which the participants reported this sensation.
Measured: 1 hour after drug was ingested
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2013 (estimated)
- Study startSep 2009
- Primary completionDec 2011
- Study completionDec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Irritable Bowel SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- Michael Camilleri
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Center for Research Resources (NCRR)
- Responsible party
- Sponsor-investigator, Michael Camilleri, Mayo Clinic
- Investigators
- Michael Camilleri, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01786109
- Sponsor's protocol ID
- 08-008314 Part B
- Other IDs
- R01DK079866, UL1RR024150
- Status last verified
- Mar 2013
- First submitted
- 5 Feb 2013
- Last updated
- 14 Mar 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 22288893Wong 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.
PubMed 21803011
Study at a glance
From the registry record, last updated by the sponsor on 14 Mar 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01786109
- Acronym / sponsor ID
- 08-008314 Part B
- Conditions
- Irritable Bowel Syndrome
- Keywords
- anandamide, cannabinoid, fatty acid amide hydrolase, gastric, motility, small bowel, sensory, motor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- Michael CamilleriUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Center for Research Resources (NCRR)
- Study start
- Sep 2009
- Primary completion
- Dec 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 7 Feb 2013 (estimated)
- Results
- Posted 13 Mar 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Dronabinol 2.5 mg | Experimental | Drug: DronabinolOne dose of dronabinol 2.5 mg was taken orally with water. |
| Dronabinol 5 mg | Experimental | Drug: DronabinolOne dose of dronabinol 5 mg was taken orally with water. |
| Placebo | Placebo comparator | Drug: PlaceboOne dose of placebo was taken orally with water. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (2 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DronabinolAlso: MarimolDronabinol is a synthetic delta-9-tetrahydrocannabinol, a nonselective cannabinoid agonist. Subjects received one dose of either 2.5 mg or 5 mg orally with water. | Drug | Dronabinol 2.5 mg, Dronabinol 5 mg |
| PlaceboPlacebo will match study drug; taken as one dose orally with water. | Drug | Placebo |
Primary outcome
Colonic Compliance at Pressure at Half-Maximum Volume (Pr 1/2)
Time frame: 1 hour after drug was ingested
Colonic compliance is a measure of the "stiffness" of the colon, that is, what pressure was needed to reach half the maximum volume of the colon. After the barostat catheter was inserted in the colon, the catheter was connected to a barostat machine. After an initial conditioning distension to 20 mm Hg, colonic compliance was measured by step-wise inflation with increments of 4 mm Hg up to 64 mm Hg. Colonic compliance was analyzed by a validated linear interpolation method. The pressure at half maximum volume serves as a summary of colonic compliance.
7 secondary outcomes
Postprandial Change in Colonic Tone
Time frame: 1 hour after ingestion of standard meal
Post-treatment Sensory Threshold for First Perception of Pain
Time frame: 1 hour after drug was ingested
Post-Treatment Overall Sensory Rating in Response to 16, 24, 32, and 40 mm Hg Distensions
Time frame: 1 hour after drug was ingested
Fasting Colonic Tone
Time frame: After 12 hour fast, before drug administered
Postprandial Colonic Motility Index
Time frame: 1 hour after ingestion of standard meal
Post-treatment Sensory Threshold for First Sensation
Time frame: 1 hour after drug was ingested
Post-Treatment Sensory Threshold for First Perception of Gas
Time frame: 1 hour after drug was ingested
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Mar 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22288893Wong 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.
- Results publication: PubMed 21803011Wong 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.
- Link to Part A of this study, results for GI and colonic motor functions, n=36Link provided by the sponsor.
Related trials for Irritable Bowel Syndrome
RecruitingObservational study
Abdominal Symptoms and Rosacea: An Observational Study on the Association Between Irritable Bowel Syndrome (IBS) and the Gut-Skin Axis
IBS (Irritable Bowel Syndrome), Rosacea
Recruiting
Stress Reduction and Lifestyle Modification in Irritable Bowel Syndrome Patients
Irritable Bowel Syndrome
Recruiting
Exercise Interventions and Dietary Advice in Fibromyalgia and IBS
Fibromyalgia, Irritable Bowel Syndrome
RecruitingPhase 2
A Study of Brenipatide (LY3537031) in Participants With Irritable Bowel Syndrome-Constipation (IBS-C)
Irritable Bowel Syndrome, Constipation
RecruitingPhase 2
A Study of Brenipatide (LY3537031) in Participants With Irritable Bowel Syndrome-Diarrhea (IBS-D)
Irritable Bowel Syndrome, Diarrhea
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Camilleri, MD principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dronabinol in people with Irritable Bowel Syndrome, run by Michael Camilleri at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Mar 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Mar 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Colonic Compliance at Pressure at Half-Maximum Volume (Pr 1/2) (time frame: 1 hour after drug was ingested). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01786109, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Mar 2013.