Effect of Lubiprostone on Small Bowel Contractions in Female Patients With Constipation Irritable Bowel Syndrome (C-IBS)
Information source: Cedars-Sinai Medical Center
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Constipation-predominant Irritable Bowel Syndrome
Intervention: Lubiprostone (Drug); Placebo (Drug)
Phase: N/A
Status: Completed
Sponsored by: Cedars-Sinai Medical Center Official(s) and/or principal investigator(s): Edy E Soffer, MD, Principal Investigator, Affiliation: Cedars-Sinai Medical Center
Summary
Irritable Bowel Syndrome (IBS) is a common disorder, defined by symptom-based diagnostic
criteria. The pathogenesis is multifactorial and gut motor dysfunction is considered to be a
contributing factor. Changes in motor patterns in the small bowel in IBS patients are
quantitative rather than qualitative with no distinct patterns to distinguish patients from
healthy individuals. Changes in motor patterns can affect transit of bowel contents. Indeed,
variation in intestinal transit was reported in patients with IBS.
Lubiprostone is a novel agent that is Food and Drug Administration (FDA) approved for the
treatment of chronic constipation. More recently 2 randomized double-blind,
placebo-controlled trials showed the drug to be effective in relieving symptoms in patients
with constipation-predominant Irritable Bowel Syndrome (C-IBS), resulting in approval for
female patients with C-IBS at a dose of 8 micrograms twice a day.
The investigators hypothesize that lubiprostone works not just as a laxative, but by
actually altering motility patterns in the small intestine of female patients with C-IBS.
These alterations can be measured through High Resolution Manometry (HRM), a new technique
that uses catheters with multiple closely spaced sensors and special software that uses
color schemes to portray a pressure gradient. This technique allows a detailed assessment of
the direction and spread of contractions. The investigators would like to use HRM to see if
lubiprostone affects intestinal contractions by giving blinded participants lubiprostone and
placebo while they are undergoing High Resolution Manometry and seeing if any changes in
contractions occur. Participants will be recruited from investigator's clinic. If
interested, potential subjects will be provided with a copy of the consent form for review.
Patients will be informed that after they have had an opportunity to review the consent
form, they may contact the study team to further discuss the research and address any
questions/concerns they have.
Participants will undergo a screening visit and a manometry visit. During the screening
visit investigators will determine eligibility, including application of inclusion/exclusion
criteria and administration of a pregnancy test. Then during the manometry visit patients
will receive two capsules, lubiprostone and placebo, three hours apart during HRM. Patients
will receive each capsule only once and will not know which order they're receiving them in.
Clinical Details
Official title: The Effect of Lubiprostone on Patterns of Contractions in the Small Bowel in Female Patients With Constipation Predominant Irritable Bowel Syndrome (C-IBS)
Study design: Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Single Blind (Subject), Primary Purpose: Basic Science
Primary outcome: A Change in Length of Spread of Antegrade Contractions After Placebo.A Change in Length of Spread of Antegrade Contractions After Lubiprostone
Secondary outcome: A Change in Length of Spread of Long Distance Propagating Contractions After Placebo.A Change in Length of Spread of Retrograde Contractions After Placebo A Change in Length of Spread of Long Distance Propagating Contractions After Lubiprostone A Change in Length of Spread of Retrograde Contractions After Lubiprostone
Detailed description:
Irritable Bowel Syndrome (IBS) is a common disorder, defined by symptom-based diagnostic
criteria. The pathogenesis is multifactorial, and gut motor dysfunction is considered to be
a contributing factor. Dysmotility affects both the small bowel and the colon. Changes in
motor patterns in the small bowel in IBS are quantitative rather than qualitative, with no
distinct patterns to distinguish patients from healthy individuals. Changes in motor
patterns can potentially affect transit of bowel contents and contribute to symptoms.
Indeed, variation in intestinal transit was reported in patients with IBS. Small bowel
transit studies, using scintigraphy, radio-opaque markers and hydrogen breath test, have
shown that transit is delayed in constipation-predominant Irritable Bowel Syndrome (C-IBS)
and accelerated in diarrhea-predominant Irritable Bowel Syndrome (D-IBS).
Lubiprostone is a novel agent that has been Food and Drug Administration (FDA) approved for
the treatment of adult males and females with chronic constipation. More recently, 2
randomized, double-blind, placebo-controlled trials showed the drug to be effective in
relieving symptoms in patients with C-IBS, resulting in approval for female patients with
C-IBS, at a dose of 8 micrograms twice a day.
The investigators hypothesize that lubiprostone works not just as a laxative, but by
actually altering motility patterns in the small intestine of female C-IBS patients. These
alterations could be measured through High Resolution Manometry (HRM), a new technique that
uses catheters with multiple, closely spaced sensors, and special software that uses color
schemes to portray a pressure gradient. This technique allows a detailed assessment of the
direction and spread of individual contractions.
The investigators would like to use HRM to see if lubiprostone affects intestinal
contractions. The investigators would like to achieve this by administering blinded
participants lubiprostone and placebo while they are undergoing HRM and seeing if any
changes in contractions occur. Participants will be recruited both from the investigator's
own clinic and by word of mouth. Patients of the investigators will be approached by a
member of the research team during a regularly scheduled clinic visit. If interested,
potential subjects will be provided with a copy of the consent form for review. Patients
will be given ample time to review the consent form with friends, family, and/or other
physicians. Patients will be informed that after they have had an opportunity to review the
consent form, they may contact the study team to schedule an appointment with one of the
co-investigators to further discuss the research and address any questions or concerns the
patient may have. Once all the potential subject's issues and concerns have been addressed,
and the individual would like to enroll in the study, an investigator or co-investigator
will obtain informed consent. Referring physicians will be asked to give their patients the
contact information for the study team and the recruitment process will proceed as described
above.
Participants will undergo two visits: a screening visit and a manometry visit. During the
screening visit we will determine eligibility, including application of inclusion/exclusion
criteria and administration of a pregnancy test. Then during the manometry visit, patients
will receive the two capsules (lubiprostone and placebo), three hours apart during HRM.
Patients will receive each capsule only once, but they will not know which order they're
receiving them in.
Patients may receive lubiprostone without participating in the research study. As
lubiprostone is FDA approved, the indications would be the same, however, patients receiving
the drug under standard of care would not be undergoing the HRM or receiving a placebo
capsule. Patients also may not be required to undergo a washout from their standard
medication before starting on lubiprostone.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Female.
Criteria:
Inclusion Criteria:
- Constipation predominant IBS (C-IBS) patients diagnosed on the basis of Rome III
criteria
- Females 18 years or older with no operations (except for appendectomy) or medical
conditions that can affect small bowel motility
- Ability to comply with the requirements of the entire study
- Patient has given written informed consent to participate and is willing to
participate in the entire study
- Patients must not be pregnant or nursing as evidenced by a negative serum pregnancy
test taken 7-10 days prior to the manometry. Any female with a positive pregnancy
test will be immediately discontinued from the study
Exclusion Criteria:
- Evidence of structural abnormality of the gastrointestinal tract or
disease/conditions. These conditions include (but are not limited to): current
evidence of history of inflammatory bowel disease (Crohn's disease or ulcerative
colitis), active diverticulitis, duodenal ulcer, erosive esophagitis, gastric ulcer,
gastroparesis, gastrointestinal malignancy, Barrett's esophagus, gastrointestinal
obstruction, carcinoid syndrome, pancreatitis, cholelithiasis, amyloidosis, ileus,
progressive systemic sclerosis (scleroderma), anorexia nervosa
- Patients with previous gastrointestinal surgery other than appendectomy or
cholecystectomy
- Evidence of cathartic colon or a history of laxative use, that in the investigator's
opinion is consistent with severe laxative dependence such that the patient is likely
to require or use laxatives during the study
- Patients with clinically diagnosed diarrhea defined as 3 stools/day that are loose or
watery in nature
- Psychosis, schizophrenia, mania, severe depression or major psychiatric illness
needing pharmacological treatment. Well-compensated depression does not exclude a
potential patient. Antidepressant medication is allowed if patient has been on a
stable dose for at least the past 3 months
- Any evidence or treatment of malignancy (other than localized basal cell, squamous
cell skin cancer or in-situ uterine cervix cancer that has been resected) within the
previous five years
- Clinical evidence (including physical examination, laboratory tests and
Electrocardiogram) of non-controlled cardiovascular, respiratory, renal, hepatic,
hematologic, neurologic, psychiatric diseases or any disease that may interfere with
the study
- Existence of surgical or medical conditions that might interfere with the absorption,
distribution, metabolism and excretion of the study drug (i. e., gastrectomy, severe
renal insufficiency)
- Symptoms of a significant clinical illness in the preceding two weeks prior to the
Screening Visit
- Use of any concurrent prohibited medications e. g., drugs that affect Gastrointestinal
(GI) motility including lubiprostone, antibiotics (erythromycin), prokinetics,
narcotic analgesics, calcium channel blockers, nitroglycerin, and antispasmodics.
Patients must not have taken prohibited medications at least 7 days prior to
manometry.
- Planned use of drugs or agents 7 days prior to the Screening Visit that affect
gastrointestinal motility and/or perceptions including erythromycin
- Use of an investigational drug or participation in an investigational study, within
30 days of the Screening Visit
- Known hypersensitivity to the drug.
- Based on investigator opinion, evidence of alcohol or drug abuse within the past two
years
Locations and Contacts
Cedars-Sinai Medical Center, Los Angeles, California 90048, United States
Additional Information
Starting date: March 2010
Last updated: November 8, 2011
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