Irritable Bowel Syndrome With Constipation (IBS-C)NCT02078323
Investigation of Linaclotide's Effect on the Bi-directional Brain and Gut Axis in IBS-C Patients
A study testing Linaclotide in people with Irritable Bowel Syndrome With Constipation (IBS-C), run by Augusta University at 1 site in United States.
Trial summary
The purpose of this study is to understand how a drug called Linaclotide improves bowel function and abdominal pain in patients with Irritable Bowel Syndrome with Constipation (IBS-C) as well as to examine whether Linaclotide alters communication between the brain and pelvic-floor region. Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Irritable Bowel Syndrome With Constipation (IBS-C)
- What is being tested?
- Linaclotide
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 39 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2014to 20 Jul 2018
- Phase
- Interventional
- 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 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- During the previous year, all patients must have recurrent abdominal discomfort or pain for at least 3 days per month in the last 3 months associated with two or more of the following symptoms (36): i) improvement with defecation; ii) onset associated with a change in frequency of stool; and/or iii) onset associated with a change in form (appearance) of stool.
- No evidence for structural diseases- (excluded by colonoscopy, sigmoidoscopy or barium enema). Patients over 50 will not be eligible to enroll unless they have had a colonoscopy, sigmoidoscopy or barium enema within ten years prior to screening. Individuals under the age of 50 would only be required to undergo one of such diagnostic procedures if they present with alarm symptoms such as rectal bleeding, unexplained weight loss or anemia). There is no plan undergo such procedures as part of this research protocol. Therefore, individuals requiring such a procedure will be referred back to their treating physician (due to reaching age 50 and requiring a general screening of colon check or any age, due to alarm symptoms) and will not be enrolled in the study.
- No evidence of metabolic problems (to be excluded by laboratory testing; a comprehensive blood count and metabolic panel are required to be within six months of screening visit. If none are available on the patient's electronic records or records provided by an external provider, we will have them complete blood testing to exclude clinically significant metabolic abnormalities). The P.I. will decide if any values that fall out of range represent clinical significance or not.
- Women of childbearing potential must agree to a urine pregnancy test at screening and to avoid pregnancy throughout the study.
- On a prospective symptom/stool diary patients reported i) presence of abdominal pain/discomfort for at least 2 days per week; ii) hard or lumpy stools >25% and loose or watery stools in < 25% of bowel movements (IBS-C); (iii) loose or watery stools in >25% of bowel movements and hard stools <25% of Bowel Movements(IBS-D); >25% of hard or loose stools within one week (IBS-M)
Who cannot join
- Patients with laxative abuse, anorexia nervosa, and bulimia;
- Patients taking opioids (e.g. codeine or morphine), antispasmodics (dicyclomine or hyoscyamine), or muscle relaxants (e.g. cyclobenzaprine). If a patient is taking any of these drugs or supplements, and the P.I. determines that they may be able to safely come off of their medication, the patient may be eligible to re-screen, pending a two week minimum washout before enrollment;
- Patients with active episodic major depression will not be enrolled and will be referred for treatment, if necessary. Patients with a history of depression and have achieved stable remission are eligible.
- Patients with comorbid illnesses, severe cardiac disease, chronic renal failure or previous gastrointestinal surgery except cholecystectomy and appendectomy;
- Patients with neurologic diseases (e.g. head injuries, epilepsy, multiple sclerosis, strokes, spinal cord injuries) or brain disorders prone to causing seizures;
- Patients experiencing impaired cognizance (mini mental score of < 15) and/or legally blind;
Show all 9Show fewer
- Women who are pregnant or likely to conceive (women with potential for pregnancy must use contraceptive measures to be included);
- Patients with ulcerative and Crohns colitis;
- Patients with rectal prolapse, anal fissure, anal surgery or inflamed hemorrhoids. Patients found to have any of these conditions are not eligible for enrollment due to the potential discomfort of probe placement. If a patient who is excluded due to anal fissure or inflamed hemorrhoids achieves full remission after the initial screening, they may be eligible for rescreening.
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to understand how a drug called Linaclotide improves bowel function and abdominal pain in patients with Irritable Bowel Syndrome with Constipation (IBS-C) as well as to examine whether Linaclotide alters communication between the brain and pelvic-floor region.
Linaclotide has been shown to improve abdominal pain and bowel symptoms in IBS-C, and is approved by the FDA for the treatment of this condition. However, how exactly this drug works to relieve abdominal pain and discomfort in humans is not clearly known. Studies in animal models suggest that patients with IBS-C have hypersensitivity in the gut.
Read more
Consequently, in IBS-C patients, there is rapid and excessive conduction of signals both from the brain and central nervous system region towards the pelvic-floor (anorectal axis) and the reverse direction. The investigators hypothesize that treatment with Linaclotide may improve/normalize these signals and thereby improve bowel symptoms.
Investigators will test this theory using a new, noninvasive (and established) method of studying this communication pathway between the brain and gut.
Read the detailed description
modulate these mechanisms and thereby improve visceral pain.
Investigators propose three specific aims:
- Examine the hyperexcitability of the afferent-pelvic floor brain axis in 60 patients with IBS by measuring the cortical evoked potentials (CEP) and sensory thresholds after electrical stimulation of the rectum and anus before and after administration of linaclotide or placebo for a period of 10 weeks.
- Study the efferent brain pelvic floor axis by stimulating the cortex with transcranial magnetic stimulation and record the anal and rectal motor evoked potentials (MEP) in 60 IBS-C patients.
- Determine the locus for neuronal modulation i.e are the neuroenteric changes due to central or peripheral neuronal sensitization or both, by evoking anal and rectal MEPs after selectively stimulating the lumbar and sacral nerves bilaterally, and by comparing segmental with transcranial-induced MEPs.
- Being tested
- Linaclotide, Placebo
- Keywords
- Irritable Bowel Syndrome with Constipation (IBS-C), Linaclotide
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LinaclotideDrug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Linaclotide | Active comparator | Linaclotide 290micrograms q day 30 min before meal for a 10 week period Receives: Drug: Linaclotide |
| placebo | Placebo comparator | Placebo q day 30 min before meal for a 10 week period Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
1: Change from baseline in Prolongation and normalization of anal CEP and rectal CEP responses at 10 weeks.
A rectal catheter will be inserted into the rectum, up to 10 cm from the anal verge. The threshold for first sensation and pain will be determined by increasing the electrical stimulation in steps of 1 mA. subsequent stimuli will be applied at an intensity of 75% of the difference between the first sensation and pain thresholds. The CEPs will be recorded in a quiet room in a semi-recumbent position. Four runs of 50 stimuli will be averaged for both the rectal and anal stimulation studies, with a 5-min rest period between each run and a 30 minute rest period between rectal and anal studies.
Measured: at baseline assessment and at 10 weeks following baseline
Change from Baseline in Prolongation and normalization of rectal MEP and anal MEP at 10 weeks.
A 70 mm figure of eight coil, positioned over the cranium's vertex. TThe coil will be placed with the anterior edge of the cross point over the region of interest, with the handle pointing backward (for midline grid points) or at an angle of 45º tangential to the scalp surface (for lateral grid points). We will perform TMS of the anorectal motor cortex and assess the anal and rectal MEPs (EMG), by using the anorectal probe.
Measured: at baseline assessment at at 10 weeks following this baseline assessment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2014 (estimated)
- Study startFeb 2014
- Primary completion4 Oct 2017
- Study completion20 Jul 2018
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 Irritable Bowel Syndrome With Constipation (IBS-C)Studies 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 N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- Augusta University
- Sponsor type
- University, hospital or other
- Collaborators
- Forest Laboratories
- Responsible party
- Principal investigator, Satish Rao, Augusta University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02078323
- Sponsor's protocol ID
- LNZ-IT-01
- Status last verified
- Jul 2018
- First submitted
- 8 Jan 2014
- Last updated
- 23 Jul 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Rao SSC, Xiang X, Yan Y, Rattanakovit K, Patcharatrakul T, Parr R, Ayyala D, Sharma A. Randomised clinical trial: linaclotide vs placebo-a study of bi-directional gut and brain axis. Aliment Pharmacol Ther. 2020 Jun;51(12):1332-1341. doi: 10.1111/apt.15772. Epub 2020 May 13.
PubMed 32406112
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation of Linaclotide's Effect on the Bi-directional Brain and Gut Axis in IBS-C Patients
- ClinicalTrials.gov ID
- NCT02078323
- Acronym / sponsor ID
- LNZ-IT-01
- Keywords
- Irritable Bowel Syndrome with Constipation (IBS-C), Linaclotide
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- Augusta UniversityUniversity, hospital or other
- Collaborators
- Forest Laboratories
- Study start
- Feb 2014
- Primary completion
- 4 Oct 2017 (actual)
- Study completion
- 20 Jul 2018 (actual)
- First posted
- 5 Mar 2014 (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 understand how a drug called Linaclotide improves bowel function and abdominal pain in patients with Irritable Bowel Syndrome with Constipation (IBS-C) as well as to examine whether Linaclotide alters communication between the brain and pelvic-floor region.
Linaclotide has been shown to improve abdominal pain and bowel symptoms in IBS-C, and is approved by the FDA for the treatment of this condition. However, how exactly this drug works to relieve abdominal pain and discomfort in humans is not clearly known. Studies in animal models suggest that patients with IBS-C have hypersensitivity in the gut.
Consequently, in IBS-C patients, there is rapid and excessive conduction of signals both from the brain and central nervous system region towards the pelvic-floor (anorectal axis) and the reverse direction. The investigators hypothesize that treatment with Linaclotide may improve/normalize these signals and thereby improve bowel symptoms.
Investigators will test this theory using a new, noninvasive (and established) method of studying this communication pathway between the brain and gut.
Detailed description
modulate these mechanisms and thereby improve visceral pain.
Investigators propose three specific aims:
- Examine the hyperexcitability of the afferent-pelvic floor brain axis in 60 patients with IBS by measuring the cortical evoked potentials (CEP) and sensory thresholds after electrical stimulation of the rectum and anus before and after administration of linaclotide or placebo for a period of 10 weeks.
- Study the efferent brain pelvic floor axis by stimulating the cortex with transcranial magnetic stimulation and record the anal and rectal motor evoked potentials (MEP) in 60 IBS-C patients.
- Determine the locus for neuronal modulation i.e are the neuroenteric changes due to central or peripheral neuronal sensitization or both, by evoking anal and rectal MEPs after selectively stimulating the lumbar and sacral nerves bilaterally, and by comparing segmental with transcranial-induced MEPs.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Linaclotide | Active comparator | Drug: LinaclotideLinaclotide 290micrograms q day 30 min before meal for a 10 week period |
| placebo | Placebo comparator | Drug: PlaceboPlacebo q day 30 min before meal for a 10 week period |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- During the previous year, all patients must have recurrent abdominal discomfort or pain for at least 3 days per month in the last 3 months associated with two or more of the following symptoms (36): i) improvement with defecation; ii) onset associated with a change in frequency of stool; and/or iii) onset associated with a change in form (appearance) of stool.
- No evidence for structural diseases- (excluded by colonoscopy, sigmoidoscopy or barium enema). Patients over 50 will not be eligible to enroll unless they have had a colonoscopy, sigmoidoscopy or barium enema within ten years prior to screening. Individuals under the age of 50 would only be required to undergo one of such diagnostic procedures if they present with alarm symptoms such as rectal bleeding, unexplained weight loss or anemia). There is no plan undergo such procedures as part of this research protocol. Therefore, individuals requiring such a procedure will be referred back to their treating physician (due to reaching age 50 and requiring a general screening of colon check or any age, due to alarm symptoms) and will not be enrolled in the study.
- No evidence of metabolic problems (to be excluded by laboratory testing; a comprehensive blood count and metabolic panel are required to be within six months of screening visit. If none are available on the patient's electronic records or records provided by an external provider, we will have them complete blood testing to exclude clinically significant metabolic abnormalities). The P.I. will decide if any values that fall out of range represent clinical significance or not.
- Women of childbearing potential must agree to a urine pregnancy test at screening and to avoid pregnancy throughout the study.
- On a prospective symptom/stool diary patients reported i) presence of abdominal pain/discomfort for at least 2 days per week; ii) hard or lumpy stools >25% and loose or watery stools in < 25% of bowel movements (IBS-C); (iii) loose or watery stools in >25% of bowel movements and hard stools <25% of Bowel Movements(IBS-D); >25% of hard or loose stools within one week (IBS-M)
Key exclusion criteria (9 listed)
- Patients with laxative abuse, anorexia nervosa, and bulimia;
- Patients taking opioids (e.g. codeine or morphine), antispasmodics (dicyclomine or hyoscyamine), or muscle relaxants (e.g. cyclobenzaprine). If a patient is taking any of these drugs or supplements, and the P.I. determines that they may be able to safely come off of their medication, the patient may be eligible to re-screen, pending a two week minimum washout before enrollment;
- Patients with active episodic major depression will not be enrolled and will be referred for treatment, if necessary. Patients with a history of depression and have achieved stable remission are eligible.
- Patients with comorbid illnesses, severe cardiac disease, chronic renal failure or previous gastrointestinal surgery except cholecystectomy and appendectomy;
- Patients with neurologic diseases (e.g. head injuries, epilepsy, multiple sclerosis, strokes, spinal cord injuries) or brain disorders prone to causing seizures;
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 |
|---|---|---|
| Linaclotide | Drug | Linaclotide |
| Placebo | Drug | placebo |
Primary outcome
1: Change from baseline in Prolongation and normalization of anal CEP and rectal CEP responses at 10 weeks.
Time frame: at baseline assessment and at 10 weeks following baseline
A rectal catheter will be inserted into the rectum, up to 10 cm from the anal verge. The threshold for first sensation and pain will be determined by increasing the electrical stimulation in steps of 1 mA. subsequent stimuli will be applied at an intensity of 75% of the difference between the first sensation and pain thresholds. The CEPs will be recorded in a quiet room in a semi-recumbent position. Four runs of 50 stimuli will be averaged for both the rectal and anal stimulation studies, with a 5-min rest period between each run and a 30 minute rest period between rectal and anal studies.
Change from Baseline in Prolongation and normalization of rectal MEP and anal MEP at 10 weeks.
Time frame: at baseline assessment at at 10 weeks following this baseline assessment
A 70 mm figure of eight coil, positioned over the cranium's vertex. TThe coil will be placed with the anterior edge of the cross point over the region of interest, with the handle pointing backward (for midline grid points) or at an angle of 45º tangential to the scalp surface (for lateral grid points). We will perform TMS of the anorectal motor cortex and assess the anal and rectal MEPs (EMG), by using the anorectal probe.
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 23 Jul 2018.
- Derived from this study: PubMed 32406112Rao SSC, Xiang X, Yan Y, Rattanakovit K, Patcharatrakul T, Parr R, Ayyala D, Sharma A. Randomised clinical trial: linaclotide vs placebo-a study of bi-directional gut and brain axis. Aliment Pharmacol Ther. 2020 Jun;51(12):1332-1341. doi: 10.1111/apt.15772. Epub 2020 May 13.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Linaclotide in people with Irritable Bowel Syndrome With Constipation (IBS-C), run by Augusta University 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 9 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 23 Jul 2018. 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.
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?
1: Change from baseline in Prolongation and normalization of anal CEP and rectal CEP responses at 10 weeks. (time frame: at baseline assessment and at 10 weeks following baseline). The study lists 2 primary outcomes in all. 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 NCT02078323, 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 23 Jul 2018.