Comparing the Effectiveness of 2 Diets for Patients With Irritable Bowel Syndrome

As irritable bowel syndrome (IBS) symptoms are often refractory to conventional therapies,
there has been increasing interest in the role of diet in IBS. Certain foods may exacerbate
symptoms of IBS. Thus, restricted diets have recently gained attention for the treatment
IBS. The mechanism by which symptoms are improved is unclear, but these diets may improve
symptoms by exerting changes on the GI microbiome.

Aims:

Primary Objective:

-Compare the proportion of patients with irritable bowel syndrome (IBS-D) reporting adequate
relief on Diet 1 vs Diet 2

Secondary Objectives:

- Assess the effects of these diets in patients with diarrhea-predominant IBS on the
gastrointestinal microbiota and blood based biomarkers.

- Compare the efficacy of Diet 1 vs Diet 2 in patients with diarrhea-predominant IBS on
pre-specified clinical and quality of life endpoints.

Methods:

This is a prospective randomized control trial of adults meeting the Rome III criteria for
irritable bowel syndrome with diarrhea (IBS-D). After a 2 week screening period and
randomization, during which the severity of symptoms will be assessed and eligibility
determined, patients will be randomized to Diet 1 vs Diet 2 for a period of 4 weeks.

The primary endpoint will be a comparison of the proportion of patients in each group
reporting adequate relief of their IBS symptoms. For the secondary clinical outcomes, a
responder definition incorporating abdominal pain and stool consistency as proposed by the
FDA will be utilized. Key IBS-D symptoms will be assessed daily and adequate relief of IBS-D
symptoms will be assessed weekly during the randomization period. We will also determine if
a difference can be detected with high probability in the relative abundance and variety of
specific bacterial taxa between the two groups before and after the 4 week dietary
intervention. In addition, blood samples will be collected before and after randomization to
measure relevant biomarkers of immune activation.

Inclusion Criteria:

- Meet Rome III criteria for IBS as assessed by a gastroenterologist:

- Fulfill the Rome III stool consistency criteria for IBS -D

- Willingness to maintain a stable dosage of IBS medications during the pretreatment
baseline period, including tricyclic antidepressants; "rescue" medications permitted
(ie Loperamide 2mg up to 4 times per day prn diarrhea)

- Ability to provide written informed consent for study participation

- Capable of independently completing all requirements of the study including returning
for required visits

- Documentation of normal colonoscopy with colon biopsies within five years

- Documentation of normal TSH, CBC, electrolyte panel

- Negative evaluation for celiac disease either with normal TTG, EMA, and/or duodenal
biopsy.

Exclusion Criteria:

- Unable to understand or provide written informed consent

- Pregnancy

- IBS with constipation or mixed subtype

- Comorbid medical problems that may affect gastrointestinal transit or motility:

- Inflammatory bowel disease

- Extraintestinal disease known to affect the gastrointestinal system (ie, scleroderma,
unstable thyroid disease, diabetes mellitus, etc.)

- Severe renal or hepatic disease

- Previous abdominal surgery other than appendectomy, cholecystectomy, and
gynecologic/urologic surgery

- Previous treatment with some diets for IBS

- Concurrent medications not permitted including probiotics, antibiotics, and narcotics

- Active participation in another form of dietary therapy

- Patients who have undergone surgery to the GI tract except appendectomy or
cholecystectomy if performed more than six months prior to enrollment.