Constipation-predominant Irritable Bowel SyndromePhase 2ChenotransitNCT00912301
Cheno Effect on Transit in Health and IBS-C
A Phase 2 study testing Sodium chenodeoxycholate (NaCDC) in people with Constipation-predominant Irritable Bowel Syndrome, run by Mayo Clinic at 1 site in United States.
Trial summary
The study hypothesis is that the naturally occurring bile acid, chenodeoxycholic acid, induces acceleration of colonic transit in health and in patients with constipation-predominant Irritable Bowel Syndrome (IBS-C). Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Constipation-predominant Irritable Bowel Syndrome
- What is being tested?
- Sodium chenodeoxycholate (NaCDC)
- 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
- Apr 2009to Dec 2009
- 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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy volunteers:
- Age (yr) 18-65
- Gender (F:M)3.5 :1
- Bowel Disease Questionnaire (BDQ) - IBS symptoms negative by Rome III criteria
- Hospital Anxiety/Depression score <8
- IBS patients:
Show all 10Show fewer
- Age (yr) 18-65
- Gender (F:M) 5 :1
- BDQ - IBS symptoms: positive by Rome III criteria
- Hospital Anxiety/Depression score: No restrictions
Who cannot join
- Abdominal surgery (except appendectomy or cholecystectomy)
- GI medications during the 48h prior to transit measurement
- Aspartate/Alanine transaminases >2 X Upper Limit of Normal (ULN)
- Other Medications except stable doses of estrogen, thyroid, low dose antidepressants of the dopaminergic or serotonergic class
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Chenodeoxycholic Acid on Gastrointestinal Transit and Colonic Functions in Health and Constipation-predominant Irritable Bowel Syndrome (IBS-C)
The study hypothesis is that the naturally occurring bile acid, chenodeoxycholic acid, induces acceleration of colonic transit in health and in patients with constipation-predominant Irritable Bowel Syndrome (IBS-C).
Read the detailed description
Hypothesis: A hydrophobic di-alpha hydroxy bile salt, sodium chenodeoxycholate (CDC), delivered in a delayed release capsule to the ileocolonic region of the colon induces acceleration of colonic transit in patients with constipation-predominant IBS.
Methods: We shall study 36 patients with IBS-C, aged 18-65 years, and each treatment group will be balanced on gender and Body Mass Index (BMI) in the randomization. All patients will be assessed for symptoms of functional gastrointestinal disorder or psychological disturbance will be characterized in a standard fashion with questionnaires (Talley et al 1989), the Psychosomatic Symptom Checklist (SCL-90) and the Hospital Anxiety and Depression Inventory [HAD (Zigmond and Snaith 1983)]. With appropriate consent, a venous blood sample will be obtained from each participant for DNA extraction. Fasting Serum 7alpha-hydroxy-4-cholesten-3-one (7alpha-CHO) will be measured in all to ensure they do not have evidence of asymptomatic bile acid malabsorption. The normal range in our lab is <61 ng/mL.
Experimental design: A randomized, double blind, placebo controlled, dose-response parallel group design, with concealed allocation. Participants will undergo an initial baseline colonic transit for 24 hours to obtain Colonic Geometric Center (GC24). Sodium chenodeoxycholate (CDC) will be delivered to the ileocolonic region to assess ascending colon and whole colonic transit in participants with IBS-C; 12 participants per group will be randomized to placebo, 0.5 or 1 gram CDC each for a period of 4 days with the transit study conducted during the last 48 hours of drug ingestion. The CDC will be placed in gelatin capsules that are coated with methacrylate (EUDRAGIT-L®), a pH-sensitive polymer that will result in release of the active ingredient in the terminal ileum.
Experimental procedure: At standardized times (hourly for first 8 hours, and at 12, 24 and 48 h), dual gamma camera scans will be obtained to measure ascending colon and overall colonic transit. Patients will fill daily diaries to evaluate stool, frequency, consistency and ease of passage.
Gastrointestinal and Colonic Transit: A validated scintigraphic method to measure gastric, small bowel, and colonic transit will be used. A methacrylate-coated capsule dissolves in the alkaline pH of the distal ileum to release 111In-labeled activated charcoal particles to evaluate colonic transit on sequential scans. Meanwhile, orally ingested 99 mTc-labeled egg meal allows measurement of gastric and small bowel transit. (Technetium [99mTc] sestamibi (trade name Cardiolite) is a pharmaceutical agent used in nuclear medicine imaging.) We have previously shown that the gastric emptying (GE) at 2 and 4 hours, colonic filling (CF) at 6 hours, and colonic geometric center (GC, weighted average of isotopic counts) in colon at 4, 24 and 48 hours provide excellent summaries of gastric emptying and colonic transit with similar diagnostic accuracy as more detailed, costly, and time-consuming analyses. The normal values for these parameters have been previously published (Cremonini et al).
Scintigraphic gastric emptying and intestinal/colonic transit analysis: A variable region of interest program will be used to measure transit, as in previous studies from our lab. Radioisotope content in each region (gastric, ascending, transverse, descending, rectosigmoid) will be corrected for decay and tissue attenuation or depth.
Anticipated Result: CDC will accelerate whole colonic transit and loosen stool form in patients with constipation predominant IBS.
- Being tested
- Sodium chenodeoxycholate (NaCDC), Placebo
- Keywords
- chenodeoxycholate, IBS, transit, colon, constipation
- Medical subject headings
- Ichthyosis Bullosa of Siemens, Constipation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sodium chenodeoxycholate (NaCDC)Drug
Also called Chenodiol
500 or 1000 milligrams NaCDC per day each for a period of 4 days
PlaceboOther
Placebo capsules with identical appearance to the study drug were prepared by the Mayo Clinic research pharmacy.
| Study group | Role | What they receive |
|---|---|---|
| NaCDC 500 mg | Experimental | Participants randomized to this arm received 500 mg NaCDC per day for 4 days. Receives: Drug: Sodium chenodeoxycholate (NaCDC) |
| NaCDC 1000 mg | Experimental | Participants randomized to this arm received 1000 mg NaCDC per day for 4 days. Receives: Drug: Sodium chenodeoxycholate (NaCDC) |
| Placebo | Placebo comparator | Participants randomized to this arm received a placebo capsule each day for 4 days. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Colonic Geometric Center at 24 Hours (GC24)
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: after 4 days of treatment
Secondary outcomes (4)
Colonic Transit at 48 Hours (GC48)
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: after 4 days of treatment
Ascending Colon Emptying (AC t_1/2)
Measured: after 4 days' treatment
Stool Consistency
The subjects rated their stool consistency using the Bristol Stool Scale. The Bristol Stool Scale is a medical aid designed to classify the form of human feces into seven categories or types. Types 1 and 2 indicate constipation with 3 and 4 being the "ideal stools" especially the latter, as they are the easiest to defecate, and 5-7 tending towards diarrhea.
Measured: after 4 days' treatment
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: after 4 days' treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2009 (estimated)
- Study startApr 2009
- Primary completionNov 2009
- Study completionDec 2009
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 Constipation-predominant 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- 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 L. Camilleri, M.D., Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00912301
- Sponsor's protocol ID
- 08-001003
- Other IDs
- R01DK054681, R01DK079866, UL1RR024150, 1RC1DK086182
- Acronym
- Chenotransit
- Status last verified
- May 2012
- First submitted
- 29 May 2009
- Last updated
- 2 Jul 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Cremonini F, Mullan BP, Camilleri M, Burton DD, Rank MR. Performance characteristics of scintigraphic transit measurements for studies of experimental therapies. Aliment Pharmacol Ther. 2002 Oct;16(10):1781-90. doi: 10.1046/j.1365-2036.2002.01344.x.
PubMed 12269971Rao AS, Wong BS, Camilleri M, Odunsi-Shiyanbade ST, McKinzie S, Ryks M, Burton D, Carlson P, Lamsam J, Singh R, Zinsmeister AR. Chenodeoxycholate in females with irritable bowel syndrome-constipation: a pharmacodynamic and pharmacogenetic analysis. Gastroenterology. 2010 Nov;139(5):1549-58, 1558.e1. doi: 10.1053/j.gastro.2010.07.052. Epub 2010 Aug 4.
PubMed 20691689
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Chenodeoxycholic Acid on Gastrointestinal Transit and Colonic Functions in Health and Constipation-predominant Irritable Bowel Syndrome (IBS-C)
- ClinicalTrials.gov ID
- NCT00912301
- Acronym / sponsor ID
- Chenotransit / 08-001003
- Keywords
- chenodeoxycholate, IBS, transit, colon, constipation
- 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
- Apr 2009
- Primary completion
- Nov 2009 (actual)
- Study completion
- Dec 2009 (actual)
- First posted
- 3 Jun 2009 (estimated)
- Results
- Posted 2 Jul 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study hypothesis is that the naturally occurring bile acid, chenodeoxycholic acid, induces acceleration of colonic transit in health and in patients with constipation-predominant Irritable Bowel Syndrome (IBS-C).
Detailed description
Hypothesis: A hydrophobic di-alpha hydroxy bile salt, sodium chenodeoxycholate (CDC), delivered in a delayed release capsule to the ileocolonic region of the colon induces acceleration of colonic transit in patients with constipation-predominant IBS.
Methods: We shall study 36 patients with IBS-C, aged 18-65 years, and each treatment group will be balanced on gender and Body Mass Index (BMI) in the randomization. All patients will be assessed for symptoms of functional gastrointestinal disorder or psychological disturbance will be characterized in a standard fashion with questionnaires (Talley et al 1989), the Psychosomatic Symptom Checklist (SCL-90) and the Hospital Anxiety and Depression Inventory [HAD (Zigmond and Snaith 1983)]. With appropriate consent, a venous blood sample will be obtained from each participant for DNA extraction. Fasting Serum 7alpha-hydroxy-4-cholesten-3-one (7alpha-CHO) will be measured in all to ensure they do not have evidence of asymptomatic bile acid malabsorption. The normal range in our lab is <61 ng/mL.
Experimental design: A randomized, double blind, placebo controlled, dose-response parallel group design, with concealed allocation. Participants will undergo an initial baseline colonic transit for 24 hours to obtain Colonic Geometric Center (GC24). Sodium chenodeoxycholate (CDC) will be delivered to the ileocolonic region to assess ascending colon and whole colonic transit in participants with IBS-C; 12 participants per group will be randomized to placebo, 0.5 or 1 gram CDC each for a period of 4 days with the transit study conducted during the last 48 hours of drug ingestion. The CDC will be placed in gelatin capsules that are coated with methacrylate (EUDRAGIT-L®), a pH-sensitive polymer that will result in release of the active ingredient in the terminal ileum.
Experimental procedure: At standardized times (hourly for first 8 hours, and at 12, 24 and 48 h), dual gamma camera scans will be obtained to measure ascending colon and overall colonic transit. Patients will fill daily diaries to evaluate stool, frequency, consistency and ease of passage.
Gastrointestinal and Colonic Transit: A validated scintigraphic method to measure gastric, small bowel, and colonic transit will be used. A methacrylate-coated capsule dissolves in the alkaline pH of the distal ileum to release 111In-labeled activated charcoal particles to evaluate colonic transit on sequential scans. Meanwhile, orally ingested 99 mTc-labeled egg meal allows measurement of gastric and small bowel transit. (Technetium [99mTc] sestamibi (trade name Cardiolite) is a pharmaceutical agent used in nuclear medicine imaging.) We have previously shown that the gastric emptying (GE) at 2 and 4 hours, colonic filling (CF) at 6 hours, and colonic geometric center (GC, weighted average of isotopic counts) in colon at 4, 24 and 48 hours provide excellent summaries of gastric emptying and colonic transit with similar diagnostic accuracy as more detailed, costly, and time-consuming analyses. The normal values for these parameters have been previously published (Cremonini et al).
Scintigraphic gastric emptying and intestinal/colonic transit analysis: A variable region of interest program will be used to measure transit, as in previous studies from our lab. Radioisotope content in each region (gastric, ascending, transverse, descending, rectosigmoid) will be corrected for decay and tissue attenuation or depth.
Anticipated Result: CDC will accelerate whole colonic transit and loosen stool form in patients with constipation predominant IBS.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| NaCDC 500 mg | Experimental | Drug: Sodium chenodeoxycholate (NaCDC)Participants randomized to this arm received 500 mg NaCDC per day for 4 days. |
| NaCDC 1000 mg | Experimental | Drug: Sodium chenodeoxycholate (NaCDC)Participants randomized to this arm received 1000 mg NaCDC per day for 4 days. |
| Placebo | Placebo comparator | Other: PlaceboParticipants randomized to this arm received a placebo capsule each day for 4 days. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Age (yr) 18-65
- Gender (F:M)3.5 :1
- Bowel Disease Questionnaire (BDQ) - IBS symptoms negative by Rome III criteria
- Hospital Anxiety/Depression score <8
- Age (yr) 18-65
Key exclusion criteria (4 listed)
- Abdominal surgery (except appendectomy or cholecystectomy)
- GI medications during the 48h prior to transit measurement
- Aspartate/Alanine transaminases >2 X Upper Limit of Normal (ULN)
- Other Medications except stable doses of estrogen, thyroid, low dose antidepressants of the dopaminergic or serotonergic class
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 |
|---|---|---|
| Sodium chenodeoxycholate (NaCDC)Also: Chenodiol500 or 1000 milligrams NaCDC per day each for a period of 4 days | Drug | NaCDC 1000 mg, NaCDC 500 mg |
| PlaceboPlacebo capsules with identical appearance to the study drug were prepared by the Mayo Clinic research pharmacy. | Other | Placebo |
Primary outcome
Colonic Geometric Center at 24 Hours (GC24)
Time frame: after 4 days of treatment
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.
4 secondary outcomes
Colonic Transit at 48 Hours (GC48)
Time frame: after 4 days of treatment
Ascending Colon Emptying (AC t_1/2)
Time frame: after 4 days' treatment
Stool Consistency
Time frame: after 4 days' treatment
Colonic Filling at 6 Hours
Time frame: after 4 days' treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 12269971Cremonini F, Mullan BP, Camilleri M, Burton DD, Rank MR. Performance characteristics of scintigraphic transit measurements for studies of experimental therapies. Aliment Pharmacol Ther. 2002 Oct;16(10):1781-90. doi: 10.1046/j.1365-2036.2002.01344.x.
- Results publication: PubMed 20691689Rao AS, Wong BS, Camilleri M, Odunsi-Shiyanbade ST, McKinzie S, Ryks M, Burton D, Carlson P, Lamsam J, Singh R, Zinsmeister AR. Chenodeoxycholate in females with irritable bowel syndrome-constipation: a pharmacodynamic and pharmacogenetic analysis. Gastroenterology. 2010 Nov;139(5):1549-58, 1558.e1. doi: 10.1053/j.gastro.2010.07.052. Epub 2010 Aug 4.
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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 L. Camilleri, M.D. 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 Sodium chenodeoxycholate (NaCDC) in people with Constipation-predominant 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 10 inclusion and 4 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 2 Jul 2012. 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 2 Jul 2012). 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 Geometric Center at 24 Hours (GC24) (time frame: after 4 days of treatment). 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 NCT00912301, 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 2 Jul 2012.