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

• Proportion of patients with adequate relief. [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  Compare the proportion of patients with irritable bowel syndrome (IBS-D) reporting adequate relief on Diet 1 v Diet 2.
  
  

• Composite endpoint [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  Composite endpoint: A responder will report a ≥30% reduction in mean daily abdominal pain score and a decrease in mean daily BSFS value of ≥1 compared to baseline for ≥2 of 4 treatment weeks. The proportion of responders between the 2 groups will be compared.
  
  
• Abdominal Pain [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  An abdominal pain responder will report a ≥30% reduction in mean daily abdominal pain score compared to baseline for ≥2 of 4 treatment weeks. The proportion of responders between the two groups will be compared. Between group differences in the proportion of patients with a ≥30% reduction in mean daily abdominal pain score compared to baseline at the end of each treatment week will also be assessed.
  
  
• Stool consistency [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  For stool consistency, a responder will be defined as one who reports a decrease in mean daily BSFS value of 1 or more compared to baseline for ≥2 of 4 treatment weeks. The proportion of responders between the 2 groups will be compared. Between group differences in the proportion of patients with a decrease in BSFS value of ≥1 compared to baseline at the end of each treatment week will also be assessed.
  
  
• Stool frequency [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  The number of bowel movements will be recorded each day by IVRS. The change from baseline in mean daily stool frequency for each treatment week will be compared for the two groups.
  
  
• Individual symptoms [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  The change from baseline in daily NRS scores averaged over each treatment week for abdominal discomfort, urgency, bloating, and fatigue will compared between the 2 groups.
  
  
• Quality of life measures [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  IBS-Quality of Life scores, Hospital Depression Anxiety Scores, Work Productivity and Activity Impairment questionnaire, and Sleep Assessment questionnaires will be compared between groups before and after the dietary intervention.
  
  
• Stool Microbiome [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

  The effect of these 2 diets on the gut microbiome (number and species) in the context of IBS is not known. A change in the microbiota may be a mechanism through which symptom response is mediated.

  We will be measuring the shift in the relative abundance (richness) and variety (diversity) of gut microbial taxa in patients with irritable bowel syndrome (IBS-D) in response to dietary intervention. Stool microbiome would be collected and analyzed using the PhyloChip™ Assay (Second Genome Inc., San Bruno, CA).

  
  
• Serum Biomarker Panel [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  Recent attempts have been made to identify a serological biomarker profile (Prometheus Therapeutics & Diagnostics, San Diego, CA) which accurately identifies patients with IBS. We intend to perform a biomarker test panel at enrollment in all study subjects to assess whether specific combinations of biomarkers can positively or negatively predict response to either diet.
  
  

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.