Safety Study of Probiotics in Adults With Irritable Bowel Syndrome

Recent studies performed outside the U.S. and/or prior to recent FDA requirements suggest
that the probiotics in VSL#3 may be effective in IBS in adults. Because there is a
significant unmet need for improved IBS therapies to prevent frequent exacerbations that
lead to unscheduled health care, we will conduct a safety study of the probiotic VSL#3.
Preliminary studies suggest that probiotics such as VSL#3 are effective in the treatment of
adults with IBS but safety studies have not been carried out. A safety study of VSL#3 has
been carried out in adult asthmatics that demonstrated no significant adverse effects.
Before a trial of VSL#3 can be performed in children with IBS, the FDA has requested that a
safety trial be conducted in adults with IBS.

Consent will be obtained from the subject.

Adults who meet the criteria for irritable bowel syndrome will be recruited and studied.
They will have been diagnosed by an adult gastroenterologist.

During a baseline one week period, the subjects will keep a diary of pain episodes, pain
severity, pain-induced interference with activity, and stooling pattern (i.e.,
pain/activity/stool diary).

Following the baseline period, the subjects will be randomized into either a 4 week or 8
week treatment period with the probiotic. The treatment will be open label. During the
treatment period, subjects will keep the diary for pain and stooling habits and a daily
record of symptoms (i.e., daily temperature monitoring).

At the end of the treatment period the pain/stool/activity diary will be repeated. Four
weeks after the treatment period ends a follow-up phone call will be made to participants to
check on their pain and stooling patterns.

Inclusion Criteria:

- Otherwise well and meet the criteria for IBS as defined by the Rome III criteria

- Ability to speak and understand English

- Telephone access

- IBS Severity Scale score of >= 75

Exclusion Criteria:

- Organic disease accounting for GI symptoms.

- Chronic illness such as renal disease, congenital heart disease, diabetes, moderate
or severe asthma, abdominal surgery, or immunosuppressed (e.g., organ transplant
recipient).

- Have received extraneous probiotic (i.e., not in a food such as yogurt) within 4
months of starting the study.

- Subjects who are taking prescription or over-the-counter medications for GI disorders
that completely relieve their symptoms because by definition these individuals do not
have IBS (e.g., antacids, proton pump inhibitors, histamine receptor antagonists).

- Medication allergies or contraindications which would preclude antimicrobial
treatment for potential infection with VSL#3 component organisms.

- Pregnancy.

- Subjects who have an individual in the household who is immunosuppressed (e.g.,
genetic immune disorder, organ transplant).

- Oral temperature > 38.0 degrees Celsius.

- Poorly controlled hypertension, history of cardiac disease, stroke/cerebral vascular
accident, bowel ischemia, or other risk factors for bowel ischemia.

- History of acute or chronic pancreatitis

- Cardiac valvular disease or other risk factor for endocarditis

- Subjects who indicate on the IBS scoring questionnaire that their pain is "severe" or
"very severe."

- Subjects who pain lasts more than 5 out of 10 days.

- Subjects whose scores indicate more than mild IBS who are over 45 years of age