Other ConstipationPhase 1NCT00934479
Intestinal Microecology in Chronic Constipation
A Phase 1 study testing Lubiprostone in people with Other Constipation and Irritable Bowel Syndrome, run by Mayo Clinic at 1 site in United States.
Trial summary
The purpose of this study is to determine whether the bacteria normally present in the bowels are different in people with constipation and to see what effect the treatment with the Food and Drug Administration (FDA) - approved drug, lubiprostone, has on these bacteria. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Other Constipation, Irritable Bowel Syndrome
- What is being tested?
- Lubiprostone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2010to Feb 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Fewer than 3 bowel movements/day and more than 3 bowel movements/week without the need for significant straining with defecation or frequent sensation of incomplete evacuation after defecation
- Absence of current or chronic gastrointestinal symptoms
- Meet Rome III criteria for chronic functional constipation
- Colonoscopy within the previous 10 years for subjects ≥ 50 years of age
- Inclusion Criteria for Constipation-Predominant IBS Patients:
- Meet Rome III criteria for C-IBS
- Colonoscopy within the previous 10 years for subjects ≥ 50 years of age
Who cannot join
- Prior gastrointestinal surgery that altered the anatomy of the esophagus, stomach, or small/large intestine (exceptions include appendectomy and cholecystectomy)
- Gastrointestinal, cardiovascular, endocrine, renal, or other chronic disease likely to affect gastrointestinal motility (e.g., uncontrolled diabetes mellitus)
- Females of childbearing age who are not practicing birth control and/or are pregnant or lactating (a urine pregnancy test will be performed on female subjects prior to lubiprostone use)
- Significant untreated psychiatric disease
- History of hypersensitivity reaction or intolerance to lubiprostone
- Inability to stop antibiotics, probiotics, and fiber supplements 1 month prior to stool sample collection
- Inability to stop proton pump inhibitors, histamine 2 receptor antagonists, prokinetic agents, narcotic analgesic agents, laxatives, and anticholinergic agents 2 weeks prior to stool sample collection
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Intestinal Microecology in Chronic Constipation
The purpose of this study is to determine whether the bacteria normally present in the bowels are different in people with constipation and to see what effect the treatment with the Food and Drug Administration (FDA) - approved drug, lubiprostone, has on these bacteria.
Read the detailed description
Chronic constipation is a common condition with a heterogeneous pathophysiology and resulting clinical manifestations. Recent evidence in the literature and collected in our laboratory confirm that there are differences in the gut microbiota between healthy individuals and those with a variety of disorders (e.g., inflammatory bowel disease, irritable bowel syndrome and obesity) suggesting that the development of certain disorders may be determined by the composition of the gut microbiota. Existing evidence warrants further investigation of the role of the microbial ecology of the human gut in constipation and an exploration of modification of the gut microbiota as a means to treat constipation by its actions on the colonic metabolism of nutrient substrates to alter colonic transit and fluid fluxes.
The proposed research will exploit our proven capability to use high-throughput molecular genomic techniques to define the intestinal microbiome in order to help define the role of the gut microbiota in chronic constipation and will explore the potential value of altering the microbiota as a management strategy in constipation. The linkage of high-throughput genomic analyses with cause-and-effect understanding of how the gut microbiota affects bowel function may lead to a reliable means to manage the gut microbiota with the intent to prevent and/or treat constipation. The immediate goals of this project are to expand on existing information about the microbial ecology in the human intestines focusing on its relationship with constipation using molecular microbiological techniques and to assess the effects on the gut microorganisms resulting from the use of the FDA-approved medication, lubiprostone. Lubiprostone is a member of a novel therapeutic class called prostones and is an orally active, bicyclic fatty acid that selectively acts on type 2 chloride channels to stimulate chloride secretion which induces a net increase in luminal fluid secretion. Unlike antibiotic, probiotic and prebiotic agents, it has no known direct effects on the gut microbiota. It is FDA-approved for the treatment of chronic constipation in men and women and for women with constipation-predominant IBS (C-IBS). The rationale for using lubiprostone to modify the gut microbiota stems from the use of similar strategies for controlling recalcitrant small intestinal bacterial overgrowth (i.e., altering fluid fluxes in the gut lumen).
We believe that this research will greatly improve our understanding of the role that the gut microbiota play in the development of constipation and potentially lead to new strategies with which to combat this common problem.
- Conditions
- Other Constipation, Irritable Bowel Syndrome
- Being tested
- Lubiprostone
- Keywords
- Chronic Constipation, Constipation Predominant Irritable Bowel Syndrome, Intestinal Microecology
- 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.
LubiprostoneDrug
Also called Amitiza
Following the initial stool and breath collections and because of differences in the FDA-approved dosing for the 2 subtypes of chronic constipation, (that is, chronic constipation (CC) versus constipation due to irritable bowel syndrome (C-IBS), the CC subjects received open-label lubiprostone 24 mcg orally twice daily for 4 weeks; while the C-IBS subjects received open-label lubiprostone 8 mcg orally twice daily for 4 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Healthy Subjects | No intervention | Healthy subjects completed a baseline 1-week diary of stool and defecatory characteristics, fasting breath for hydrogen and methane and a stool sample for pyrosequencing. Otherwise, the healthy subjects received no intervention. |
| Constipated Subjects | Experimental | Subjects with constipation included those with chronic constipation (CC) and those with constipation predominant irritable bowel syndrome (C-IBS). They completed a baseline 1-week diary of stool and defecatory characteristics, fasting breath for hydrogen and methane and a stool sample for pyrosequencing.
Following baseline test and because of differences in the FDA-approved dosing for the 2 subtypes of chronic constipation, the CC subjects received open-label lubiprostone 24 mcg orally twice daily for 4 weeks; while the C-IBS subjects received open-label lubiprostone 8 mcg orally twice daily for 4 weeks.
Following the 4-weeks treatment with lubiprostone, they completed another stool diary, fasting breath test, and stool sample for pyrosequencing. Receives: Drug: Lubiprostone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identification of specific microorganisms associated with chronic constipation in comparison to healthy subjects and those with C-IBS
Measured: 5 weeks
Secondary outcomes (1)
Evaluate changes in the gut microbiota after lubiprostone treatment in the chronic constipation subjects and those with C-IBS
Measured: 5 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2009 (estimated)
- Study startApr 2010
- Primary completionFeb 2012
- Study completionFeb 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Other ConstipationStudies 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 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- Arizona State University, Takeda Pharmaceuticals North America, Inc.
- Responsible party
- Principal investigator, John K. DiBaise, Mayo Clinic
- Investigators
- John K. DiBaise, M.D., Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00934479
- Sponsor's protocol ID
- 09-001281
- Status last verified
- Jul 2013
- First submitted
- 6 Jul 2009
- Last updated
- 17 Jul 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Kang DW, DiBaise JK, Ilhan ZE, Crowell MD, Rideout JR, Caporaso JG, Rittmann BE, Krajmalnik-Brown R. Gut microbial and short-chain fatty acid profiles in adults with chronic constipation before and after treatment with lubiprostone. Anaerobe. 2015 Jun;33:33-41. doi: 10.1016/j.anaerobe.2015.01.005. Epub 2015 Jan 21.
PubMed 25617726
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Intestinal Microecology in Chronic Constipation
- ClinicalTrials.gov ID
- NCT00934479
- Acronym / sponsor ID
- 09-001281
- Conditions
- Other Constipation, Irritable Bowel Syndrome
- Keywords
- Chronic Constipation, Constipation Predominant Irritable Bowel Syndrome, Intestinal Microecology
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- Arizona State University, Takeda Pharmaceuticals North America, Inc.
- Study start
- Apr 2010
- Primary completion
- Feb 2012 (actual)
- Study completion
- Feb 2012 (actual)
- First posted
- 8 Jul 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether the bacteria normally present in the bowels are different in people with constipation and to see what effect the treatment with the Food and Drug Administration (FDA) - approved drug, lubiprostone, has on these bacteria.
Detailed description
Chronic constipation is a common condition with a heterogeneous pathophysiology and resulting clinical manifestations. Recent evidence in the literature and collected in our laboratory confirm that there are differences in the gut microbiota between healthy individuals and those with a variety of disorders (e.g., inflammatory bowel disease, irritable bowel syndrome and obesity) suggesting that the development of certain disorders may be determined by the composition of the gut microbiota. Existing evidence warrants further investigation of the role of the microbial ecology of the human gut in constipation and an exploration of modification of the gut microbiota as a means to treat constipation by its actions on the colonic metabolism of nutrient substrates to alter colonic transit and fluid fluxes.
The proposed research will exploit our proven capability to use high-throughput molecular genomic techniques to define the intestinal microbiome in order to help define the role of the gut microbiota in chronic constipation and will explore the potential value of altering the microbiota as a management strategy in constipation. The linkage of high-throughput genomic analyses with cause-and-effect understanding of how the gut microbiota affects bowel function may lead to a reliable means to manage the gut microbiota with the intent to prevent and/or treat constipation. The immediate goals of this project are to expand on existing information about the microbial ecology in the human intestines focusing on its relationship with constipation using molecular microbiological techniques and to assess the effects on the gut microorganisms resulting from the use of the FDA-approved medication, lubiprostone. Lubiprostone is a member of a novel therapeutic class called prostones and is an orally active, bicyclic fatty acid that selectively acts on type 2 chloride channels to stimulate chloride secretion which induces a net increase in luminal fluid secretion. Unlike antibiotic, probiotic and prebiotic agents, it has no known direct effects on the gut microbiota. It is FDA-approved for the treatment of chronic constipation in men and women and for women with constipation-predominant IBS (C-IBS). The rationale for using lubiprostone to modify the gut microbiota stems from the use of similar strategies for controlling recalcitrant small intestinal bacterial overgrowth (i.e., altering fluid fluxes in the gut lumen).
We believe that this research will greatly improve our understanding of the role that the gut microbiota play in the development of constipation and potentially lead to new strategies with which to combat this common problem.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Healthy Subjects | No intervention | –Healthy subjects completed a baseline 1-week diary of stool and defecatory characteristics, fasting breath for hydrogen and methane and a stool sample for pyrosequencing. Otherwise, the healthy subjects received no intervention. |
| Constipated Subjects | Experimental | Drug: LubiprostoneSubjects with constipation included those with chronic constipation (CC) and those with constipation predominant irritable bowel syndrome (C-IBS). They completed a baseline 1-week diary of stool and defecatory characteristics, fasting breath for hydrogen and methane and a stool sample for pyrosequencing. Following baseline test and because of differences in the FDA-approved dosing for the 2 subtypes of chronic constipation, the CC subjects received open-label lubiprostone 24 mcg orally twice daily for 4 weeks; while the C-IBS subjects received open-label lubiprostone 8 mcg orally twice daily for 4 weeks. Following the 4-weeks treatment with lubiprostone, they completed another stool diary, fasting breath test, and stool sample for pyrosequencing. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Fewer than 3 bowel movements/day and more than 3 bowel movements/week without the need for significant straining with defecation or frequent sensation of incomplete evacuation after defecation
- Absence of current or chronic gastrointestinal symptoms
- Meet Rome III criteria for chronic functional constipation
- Colonoscopy within the previous 10 years for subjects ≥ 50 years of age
- Meet Rome III criteria for C-IBS
Key exclusion criteria (7 listed)
- Prior gastrointestinal surgery that altered the anatomy of the esophagus, stomach, or small/large intestine (exceptions include appendectomy and cholecystectomy)
- Gastrointestinal, cardiovascular, endocrine, renal, or other chronic disease likely to affect gastrointestinal motility (e.g., uncontrolled diabetes mellitus)
- Females of childbearing age who are not practicing birth control and/or are pregnant or lactating (a urine pregnancy test will be performed on female subjects prior to lubiprostone use)
- Significant untreated psychiatric disease
- History of hypersensitivity reaction or intolerance to lubiprostone
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 |
|---|---|---|
| LubiprostoneAlso: AmitizaFollowing the initial stool and breath collections and because of differences in the FDA-approved dosing for the 2 subtypes of chronic constipation, (that is, chronic constipation (CC) versus constipation due to irritable bowel syndrome (C-IBS), the CC subjects received open-label lubiprostone 24 mcg orally twice daily for 4 weeks; while the C-IBS subjects received open-label lubiprostone 8 mcg orally twice daily for 4 weeks. | Drug | Constipated Subjects |
Primary outcome
Identification of specific microorganisms associated with chronic constipation in comparison to healthy subjects and those with C-IBS
Time frame: 5 weeks
1 secondary outcome
Evaluate changes in the gut microbiota after lubiprostone treatment in the chronic constipation subjects and those with C-IBS
Time frame: 5 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2013.
- Derived from this study: PubMed 25617726Kang DW, DiBaise JK, Ilhan ZE, Crowell MD, Rideout JR, Caporaso JG, Rittmann BE, Krajmalnik-Brown R. Gut microbial and short-chain fatty acid profiles in adults with chronic constipation before and after treatment with lubiprostone. Anaerobe. 2015 Jun;33:33-41. doi: 10.1016/j.anaerobe.2015.01.005. Epub 2015 Jan 21.
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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.
John K. DiBaise, 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 1 study testing Lubiprostone in people with Other Constipation and 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 7 inclusion and 7 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 17 Jul 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Identification of specific microorganisms associated with chronic constipation in comparison to healthy subjects and those with C-IBS (time frame: 5 weeks). 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 NCT00934479, which also lists 1 linked publication.
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 17 Jul 2013.