Irritable Bowel SyndromePhase 2NCT01253408
Effect of Cannabinoid Agonist on Gastrointestinal and Colonic Motor Functions in Patients With Irritable Bowel Syndrome (IBS)
A Phase 2 study testing Dronabinol in people with Irritable Bowel Syndrome, run by Mayo Clinic 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
- 36 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)
- Baseline Geometric Center at 24 hours is greater/equal to 2.0
- Baseline Geometric Center at 48 hours is greater/equal to 3.9
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Study of the Effect of Cannabinoid Agonist on Gastrointestinal and Colonic Motor and Sensory Functions in Patients With 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).
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.
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 are unmet clinical needs and 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 type 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. The aims of the study are to compare the effects of two doses of the cannabinoid agonist, dronabinol (5 and 10 mg/day) and placebo on gastrointestinal and colonic motor and sensory functions in IBS. Also, to determine whether variations in the fatty acid amide hydrolase (FAAH) gene and the monoacylglycerol lipase (MGLL) gene (for the rate limiting enzyme, monoacylglycerol lipase, for another endocannabinoid, 2-arachidonyl glycerol) influence the pharmacological effect of cannabinoid modulation on gastrointestinal motor and sensory functions.
All participants underwent the following procedures:
- Documentation of eligibility, screening questionnaires, and physical examination within the month prior to the study. The physical exam included standard rectal and pelvic floor examinations to exclude rectal evacuation disorder. This was necessary to ensure the diarrhea ws not secondary to "retention of stool with overflow."
- Baseline colonic transit measurement (Geometric Center 24-h and 48-h), off treatment.
- Treatment days corresponded to the scintigraphic transit testing days (days 1 and 2) with participants receiving the medication to which they were randomized. Scintigraphic measurements of gastric, small bowel, and colonic transit were conducted, using a previously validated method on days 1 and 2, and were completed with a fasting 48-h scan on day 3 when no medication was administered. On days 1 and 2, the morning dose of medication was ingested in the research laboratory, with the participant fasting. On day 1, the morning dose of medication was administered together with the delayed release capsule containing an isotope labeled activated charcoal used to measure colonic transit. On day 2, the morning dose of medication was given after the 24-h scan. The evening doses on days 1 and 2 were ingested by participants at bed time in their homes.
- With appropriate consent, a venous blood sample was to be obtained from all participants for DNA extraction and pharmacogenomic studies.
- Conditions
- Irritable Bowel Syndrome
- Being tested
- Dronabinol, Placebo
- Keywords
- anandamide, cannabinoid, fatty acid amide hydrolase, gastric, motility, small bowel
- 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 Marinol
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.
PlaceboDrug
Placebo will match study drug; taken orally with water twice per day for two days.
| Study group | Role | What they receive |
|---|---|---|
| Dronabinol 2.5 mg bid | Experimental | Dronabinol 2.5 mg will be taken orally with water twice per day for two days. Receives: Drug: Dronabinol |
| Dronabinol 5 mg bid | Experimental | Dronabinol 5 mg will be taken orally with water twice per day for two days. Receives: Drug: Dronabinol |
| Placebo | Placebo comparator | Placebo will be taken orally with water twice per day for two days. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 hours
Secondary outcomes (5)
Colonic Transit Geometric Center
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.
Measured: 28, 32, and 48 hours
Gastric Emptying Half-Time (t1/2)
The time for half of the ingested solids or liquids to leave the stomach.
Measured: Approximately 2 hours after radiolabel meal is ingested
Colonic Filling at 6 Hours
Percent of the radio-labeled meal that reached the colon at 6 hours, indirectly reflecting small bowel transit time.
Measured: 6 hours after radiolabeled meal was ingested
Ascending Colon Emptying T 1/2
Ascending colon emptying t1/2 will be estimated by power exponential analysis of the proportionate emptying over time of counts from the colon. The primary data for this analysis will be the proportion of decay and depth-corrected counts in the ascending colon on the hourly scans on the first day of transit measurement and the 48 hour data.
Measured: 48 hours after radiolabeled meal was ingested
Gastric Emptying at 2 and 4 Hours
Proportion of stomach contents emptied at a 2 and 4 hours.
Measured: 2, 4 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2010 (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.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- 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
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Center for Research Resources (NCRR)
- Investigators
- Michael Camilleri, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01253408
- Sponsor's protocol ID
- 08-008314 Part A
- Other IDs
- R01DK079866, UL1RR024150
- Status last verified
- Mar 2013
- First submitted
- 18 Nov 2010
- Last updated
- 7 May 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 21803011Wong 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 22288893
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of the Effect of Cannabinoid Agonist on Gastrointestinal and Colonic Motor and Sensory Functions in Patients With Irritable Bowel Syndrome
- ClinicalTrials.gov ID
- NCT01253408
- Acronym / sponsor ID
- 08-008314 Part A
- Conditions
- Irritable Bowel Syndrome
- Keywords
- anandamide, cannabinoid, fatty acid amide hydrolase, gastric, motility, small bowel
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, 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
- 3 Dec 2010 (estimated)
- Results
- Posted 7 May 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).
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.
Detailed description
Irritable bowel syndrome (IBS) affects about 15% of the U.S. population. Despite increasing understanding of the pathophysiology of IBS, there are unmet clinical needs and 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 type 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. The aims of the study are to compare the effects of two doses of the cannabinoid agonist, dronabinol (5 and 10 mg/day) and placebo on gastrointestinal and colonic motor and sensory functions in IBS. Also, to determine whether variations in the fatty acid amide hydrolase (FAAH) gene and the monoacylglycerol lipase (MGLL) gene (for the rate limiting enzyme, monoacylglycerol lipase, for another endocannabinoid, 2-arachidonyl glycerol) influence the pharmacological effect of cannabinoid modulation on gastrointestinal motor and sensory functions.
All participants underwent the following procedures:
- Documentation of eligibility, screening questionnaires, and physical examination within the month prior to the study. The physical exam included standard rectal and pelvic floor examinations to exclude rectal evacuation disorder. This was necessary to ensure the diarrhea ws not secondary to "retention of stool with overflow."
- Baseline colonic transit measurement (Geometric Center 24-h and 48-h), off treatment.
- Treatment days corresponded to the scintigraphic transit testing days (days 1 and 2) with participants receiving the medication to which they were randomized. Scintigraphic measurements of gastric, small bowel, and colonic transit were conducted, using a previously validated method on days 1 and 2, and were completed with a fasting 48-h scan on day 3 when no medication was administered. On days 1 and 2, the morning dose of medication was ingested in the research laboratory, with the participant fasting. On day 1, the morning dose of medication was administered together with the delayed release capsule containing an isotope labeled activated charcoal used to measure colonic transit. On day 2, the morning dose of medication was given after the 24-h scan. The evening doses on days 1 and 2 were ingested by participants at bed time in their homes.
- With appropriate consent, a venous blood sample was to be obtained from all participants for DNA extraction and pharmacogenomic studies.
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Dronabinol 2.5 mg bid | Experimental | Drug: DronabinolDronabinol 2.5 mg will be taken orally with water twice per day for two days. |
| Dronabinol 5 mg bid | Experimental | Drug: DronabinolDronabinol 5 mg will be taken orally with water twice per day for two days. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo will be taken orally with water twice per day for two days. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (2 listed)
- 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.
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: MarinolDronabinol 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. | Drug | Dronabinol 2.5 mg bid, Dronabinol 5 mg bid |
| PlaceboPlacebo will match study drug; taken orally with water twice per day for two days. | Drug | Placebo |
Primary outcome
Colonic Transit Geometric Center at 24 Hours
Time frame: 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.
5 secondary outcomes
Colonic Transit Geometric Center
Time frame: 28, 32, and 48 hours
Gastric Emptying Half-Time (t1/2)
Time frame: Approximately 2 hours after radiolabel meal is ingested
Colonic Filling at 6 Hours
Time frame: 6 hours after radiolabeled meal was ingested
Ascending Colon Emptying T 1/2
Time frame: 48 hours after radiolabeled meal was ingested
Gastric Emptying at 2 and 4 Hours
Time frame: 2, 4 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: 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.
- Results publication: 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.
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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 Mayo Clinic 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 5 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 7 May 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 7 May 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 Transit Geometric Center at 24 Hours (time frame: 24 hours). 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 NCT01253408, 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 7 May 2013.