The Role of Fiber in the Prevention and Treatment of Fecal Incontinence

The purpose of this study is to determine the effect of fiber supplementation on the fecal metagenome and metabolome in relation to symptoms and anorectal physiology in post-menopausal women with irritable bowel syndrome with diarrhea suffering from liquid stool fecal incontinence (FI.)

Study Overview

• Status: Recruiting
• Conditions: Irritable Bowel Syndrome With Diarrhea; Fecal Incontinence
• Intervention / Treatment: Dietary supplement: Psyllium

Detailed Description

This is an open-label, single-arm study at Massachusetts General Hospital that aims to recruit post-menopausal female patients with solid stool fecal incontinence. The investigators hope that subjects taking a daily fiber supplement will experience reduced episodes and symptoms of fecal incontinence, measured through quality of life questionnaires and daily stool and food diaries. Subjects will undergo 2 anorectal manometry procedures. Stool samples will also be collected for metabolomic and metagenomic analysis.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kyle Staller, MD MPH; Phone Number: 617-724-6038; Email: kstaller@mgh.harvard.edu
• Study Contact Backup: Name: Braden Kuo, MD; Phone Number: 617-726-5525; Email: bkuo@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Libby Gardner; Phone Number: 617-643-5742; Email: eggardner@mgh.harvard.edu
      • Sub-Investigator: Braden Kuo, MD
      • Principal Investigator: Kyle Staller, MD, MPH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Female, post-menopausal
2. Age 50-90 years old
3. BMI >18.5 and <40 kg/m2
4. Rome IV criteria for liquid stool fecal incontinence occurring at least twice per month
5. At least one FI episode during the run-in period
6. Compliant with reporting during run-in (completion of two 3-day food diaries and two 7-day bowel diaries)
7. Submission of two stool samples during the run-in period
8. Ability to follow verbal and written instructions
9. Informed consent form signed by the subjects

Exclusion Criteria:

1. Less than two episodes per month of liquid stool fecal incontinence
2. Non-compliance with reporting during run-in
3. Patients reporting laxative, enema, and/or suppository usage during the run-in period
4. GI tract structural abnormality that would increase likelihood of obstruction
5. Dysphagia, swallowing disorder, or history of esophageal structural lesions
6. History of GI lumen surgery within 60 days prior to entry into the study
7. Neurological disorders, metabolic disorders, or other significant disease that would impair their ability to participate in the study
8. Inability to tolerate or contraindication to performance of anorectal manometry
9. Celiac disease, Crohn's disease, ulcerative colitis
10. Current anorectal fistula and/or abscess
11. Age <50 or >90
12. BMI of <18.5 or ≥40 kg/m2
13. History of allergic reaction to psyllium
14. Previous trial of soluble fiber supplementation for fecal incontinence within the previous 30 days
15. History of sacral nerve stimulator or artificial anal sphincter placement
16. Administration of investigational products within 1 month prior to Screening Visit
17. Subjects anticipating surgical intervention during the study

19. History of intestinal stricture (e.g., Crohn's disease) 20. History of intestinal obstruction or subjects at high risk of intestinal obstruction including suspected small bowel adhesions 21. History of malabsorption 22. Any other clinically significant disease interfering with the assessments of psyllium, according to the Investigator (e.g., disease requiring corrective treatment, potentially leading to study discontinuation) 23. Any relevant biochemical abnormality interfering with the assessments of psyllium, according to the Investigator 24. Patients with metallic implants within a 30 cm radius of the TAMS electromagnetic coil 25. Currently on opioids 26. Patients with severe cardiac disease, chronic renal failure, or previous GI surgery EXCEPT cholecystectomy, appendectomy, Nissen fundoplication, and partial colectomy 27. Patients with neurological diseases and increased intracranial pressure 28. Patients with impaired cognizance 29. Previous pelvic surgery/radiation, radical hysterectomy 30. Patients with Ulcerative Colitis or Crohn's Disease 31. History of or current rectal prolapse 32. Previous history of anal fissure, anal surgery (abscess), congenital anorectal malformation, fistulae or inflamed hemorrhoids 33. Pregnant women 34. Use of antibiotics in previous 60 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Psyllium fiber supplement treatment; All patients will receive psyllium fiber in the form of edible bars, 7g, twice a day to total 14g per day.	Dietary supplement: Psyllium; Psyllium fiber powder baked into a bar is commonly used as a first line of treatment for patients with fecal incontinence.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stool metagenomics	Sequence-based microbial community surveys will be carried out to characterize rare taxa and understand relationships between community membership and function from stool samples collected from baseline to the final visit.	Change from baseline to final visit. Through study completion, up to 6 weeks.
Stool microbiome	Stool samples will be shipped to Metabolon Inc, for metabolomics profiling on a well-validated high-throughput metabolomics platform. Sample prep and global metabolomics profiling will be conducted using four liquid chromatography tandem mass spectrometry methods that measure four complementary sets of metabolite classes. Metabolite peaks are quantified using area-under-the curve. Raw area counts for each metabolite in each sample are normalized to correct for variation resulting from inter-day tuning differences by setting the medians to 1.0 for each run. Metabolites are identified by automated comparison of the ion features in the experimental samples to a reference library of ~8,000 chemical standard entries that are curated for quality control using Metabolon software. Coefficients of variations (CVs) will be measured in blinded quality control samples randomly distributed among study samples, and we will analyze and control for batch variation.	Change from baseline to final visit. Through study completion, up to 6 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fecal incontinence severity index (FISI)	Questionnaire about the severity of symptoms in those with fecal incontinence. Consists of 4 questions, each rated on a scale of 1 to 6. Lower scores indicate higher severity of symptoms. (Min, 4, max 24)	Change from baseline to final visit. Through study completion, up to 6 weeks.
Fecal Incontinence quality of life (FIQL)	Questionnaire about the quality of life of those with fecal incontinence. Questions are rated from 1 to 4 in each section. Lower rating represent worse quality of life. Subscales exist for lifestyle, coping behavior, embarrassment, and depression. There is no total score for this outcome, only subscores per section. (Min 4, max, 16)	Change from baseline to final visit. Through study completion, up to 6 weeks.
Anorectal manometry parameters	Anorectal manometry (ARM) procedure performed to measure the change in anal and rectal muscle function and sensation at baseline and at the final visit.	Change from baseline to final visit. Through study completion, up to 6 weeks.
Translumbosacral anorectal magnetic stimulation	Translumbosacral anorectal magnetic stimulation (TAMS) performed during the ARM procedure to measure the change in the nerve conduction between the spinal cord and rectum at baseline and at the final visit.	Change from baseline to final visit. Through study completion, up to 6 weeks.
Global assessment of relief	A 7-point scale indicating overall fecal incontinence symptom relief where 1 represents completely relieved and 7 represents completely worse.	Change from baseline to final visit. Through study completion, up to 6 weeks.
Bloating scale	A 10-point scale indicating bloating severity where 0 represents the least severity and 10 represents the most severity	Change from baseline to final visit. Through study completion, up to 6 weeks.
Urgency scale	A 10-point scale indicating urgency severity where 0 represents the least severity and 10 represents the most severity	Change from baseline to final visit. Through study completion, up to 6 weeks.
Flatus scale	A 10-point scale indicating flatus severity where 0 represents the least severity and 10 represents the most severity	Change from baseline to final visit. Through study completion, up to 6 weeks.
Waist circumference measurement (cm)	A measure of the subject's waist circumference in the area where the most bloating is experienced	Change from baseline to final visit. Through study completion, up to 6 weeks.

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Kyle Staller, MD MPH, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2021
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: March 8, 2021
• First Submitted That Met QC Criteria: March 16, 2021
• First Posted (Actual): March 19, 2021

Study Record Updates

• Last Update Posted (Actual): March 22, 2024
• Last Update Submitted That Met QC Criteria: March 21, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Irritable Bowel Syndrome; IBS; IBS-D; Fecal Incontinence; FI; Irritable Bowel Syndrome with Diarrhea
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Syndrome; Irritable Bowel Syndrome; Diarrhea; Fecal Incontinence; Gastrointestinal Agents; Cathartics; Psyllium
• Other Study ID Numbers: 2021P000691

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No