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

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-IBS (IBS-C) and accelerated in
diarrhea predominant-IBS (IBS-D).

Lubiprostone is a novel agent that has been 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.

We hypothesize that lubiprostone works not just as a laxative, but by actually altering
motility patterns in the small intestine of female IBS-C 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.

We would like to use HRM to see if lubiprostone affects intestinal contractions. We 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.