Low FODMAP Plus PEG 3350 for the Treatment of Patients With Irritable Bowel Syndrome-Constipation

A. Specific Aims: While a diet low in fermentable oligo, di, monosaccharides and polyols
(FODMAPs) has gained popularity as a treatment for patients with Irritable Bowel Syndrome and
diarrhea (IBS-D), the impact of this diet on patients with IBS and constipation (IBS-C) is
unknown. We propose a randomized, controlled trial in IBS-C patients to compare the efficacy
of PEG 3350 and the low FODMAP diet to PEG 3350 and a sham diet. We hypothesize that:

1. The PEG 3350 and low FODMAP diet group will achieve greater improvements in abdominal
symptoms including pain, discomfort, and bloating than the group receiving PEG 3350 and
the sham diet.

2. The PEG 3350 and low FODMAP diet group will achieve greater improvements in IBS related
quality of life and anxiety than the group receiving PEG 3350 and the sham diet.

3. Both strategies will improve constipation related complaints including stool frequency,
stool consistency and straining to a similar degree.

We plan to test our central hypothesis and, thereby, accomplish the objective of this
application by pursuing the following 2 specific aims:

Aim 1: Compare the proportion of patients with IBS-C on a diet of low FODMAP diet plus PEG
3350 vs. sham diet plus PEG 3350 reporting an improvement of abdominal pain. Our working
hypothesis is that a higher proportion of patients randomized to the low FODMAP diet plus PEG
3350 will experience a reduction in the abdominal pain when compared to PEG 3350 plus sham
diet alone.

Aim 2: Compare the efficacy of the low FODMAP diet plus PEG 3350 vs. sham diet plus PEG 3350
on pre-specified key clinical and disease specific quality of life endpoints in patients with
IBS-C. Through our randomized controlled trial, we will assess the impact of the dietary
interventions on stool consistency, stool frequency, and bloating and quality of life
endpoints.

A positive result to this study would have significant impact on the treatment of patients
with IBS by expanding the indications for the low FODMAP diet to all affected patients,
regardless of bowel subtype. This would be particularly relevant to IBS-C patients for whom
we currently have few evidence-based diet recommendations outside of increasing fiber intake.

Inclusion Criteria:

1. Subjects aged 18 and older meeting the Rome IV criteria for IBS-C*:

• Recurrent abdominal pain, on average, at least 1 day/week in the last 3 months,
associated with two or more of the following:

1. related to defecation

2. associated with a change in the frequency of stool (reduction of stools)

3. associated with a change in the form of stool (hard or lumpy stools) AND >25% hard
stools and <25% loose stools * Criteria fulfilled for the last 3 months

Exclusion Criteria:

- any other IBS subtype other than IBS-C

- >3 spontaneous bowel movements during the last 7 days of run-in

- Have cognitive dysfunction or unable to understand or provide written informed consent

- Pregnancy (evaluated by self-report)

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

- Inflammatory bowel disease

- Extra-intestinal disease known to affect the gastrointestinal system (i.e.,
scleroderma, unstable thyroid disease, etc.)

- Severe renal or hepatic disease

- Previous abdominal surgery other than appendectomy, cholecystectomy, and
gynecologic/urologic surgery if performed more than six months prior to enrollment

- Previous treatment with the low FODMAP diet under a dietician guidance

- Concurrent medications not permitted including probiotics, antibiotics, prescription
or over-the-counter medication for IBS, and narcotics

- New antidepressant use (less than 3 months on stable dose)

- Active participation in another form of dietary therapy