Effect of Lubiprostone on Small Bowel Contractions in Female Patients With Constipation Irritable Bowel Syndrome (C-IBS)

NCT01085643 | Completed Results

• 1 other identifier: 17482
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Constipation-predominant Irritable Bowel Syndrome

Keywords

IBS; Lubiprostone; Small Bowel; High Resolution Manometry; Delayed Intestinal Transit

Outcome Measures

Primary Outcomes (2)

• A Change in Length of Spread of Antegrade Contractions After Placebo.

  Pressure waves are considered to represent contractions if the rise in intraluminal pressure is \>10mmHg above the baseline. They are considered propagating if they are recorded in more than one channel and occur within a time frame that allowed a minimal velocity of 0.7cm/sec and maximum velocity of 4cm/sec. All contractions, their direction (antegrade, stationary or retrograde) and the length of spread will be determined for each sequence at baseline (after taking Placebo)and within the following 3 hours.

  baseline and within the following 3 hours

• A Change in Length of Spread of Antegrade Contractions After Lubiprostone

  Pressure waves are considered to represent contractions if the rise in intraluminal pressure is \>10mmHg above the baseline. They are considered propagating if they are recorded in more than one channel and occur within a time frame that allowed a minimal velocity of 0.7cm/sec and maximum velocity of 4cm/sec. All contractions, their direction (antegrade, stationary or retrograde) and the length of spread will be determined for each sequence at baseline (after taking Placebo)and within the following 3 hours.

  baseline and within the following 3 hours

Secondary Outcomes (4)

• A Change in Length of Spread of Long Distance Propagating Contractions After Placebo.

  baseline and within the following 3 hours

• A Change in Length of Spread of Retrograde Contractions After Placebo

  baseline and within the following 3 hours

• A Change in Length of Spread of Long Distance Propagating Contractions After Lubiprostone

  baseline and within the following 3 hours

• A Change in Length of Spread of Retrograde Contractions After Lubiprostone

  baseline and within the following 3 hours

Study Arms (2)

Lubiprostone

ACTIVE COMPARATOR

Same patients are included in both the Lubiprostone arm and the Placebo arm. The reason why the same patients are assigned to two arms is because an effect comparison is done after taking the placebo and later after taking the lubiprostone.

Drug: Lubiprostone

Placebo

PLACEBO COMPARATOR

Same patients are included in both the Lubiprostone arm and the Placebo arm. The reason why the same patients are assigned to two arms is because an effect comparison is done after taking the placebo and later after taking the lubiprostone.

Drug: Placebo

Interventions

Lubiprostone DRUG

24mcg PO taken once

Also known as: Amitiza

Lubiprostone

Placebo DRUG

24mcg placebo capsule taken once

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead
• Takeda Pharmaceuticals North America, Inc.: collaborator

Study Sites (1)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

MeSH Terms

Interventions

Lubiprostone

Intervention Hierarchy (Ancestors)

Alprostadil; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Fatty Acids; Lipids

Limitations and Caveats

Limited time period resulting in recruitment of only 4 patients.

Results Point of Contact

• Title: Edy Soffer, MD
• Organization: Cedars-Sinai Medical Center

edy.soffer@cshs.org

(310) 423-6143

Study Officials

• Edy E Soffer, MD

  Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: March 11, 2010
• First Posted: March 12, 2010
• Study Start: March 1, 2010
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: December 12, 2011
• Results First Posted: December 12, 2011

Record last verified: 2011-11

Locations

US (1)