A Pilot Study Examining Low Sulfur Diet as Treatment for Persistent Symptoms in Quiescent Crohn's Disease

The goal of this study is to learn about a low sulfur diet in patients with Crohn's disease. Study participants will be randomized to receive a low sulfur diet or usual diet for 8 weeks. Participants will work with study nutritionists and receive dietary educational materials. Participants will attend 2 in-person visits as well as 6 phone visits during the study. In addition, subjects will undergo testing, including a test to measure rectal sensation, a test to look for small intestinal bacterial overgrowth, and a test to measure leaky gut.

Study Overview

• Status: Recruiting
• Conditions: Crohn's Disease in Remission
• Intervention / Treatment: Other: Low Sulfur Diet; Other: Usual Diet

Detailed Description

Even in the absence of active inflammation, persistent symptoms are reported in up to 46% of inflammatory bowel disease (IBD) patients, especially in Crohn's disease (CD). While persistent symptoms in quiescent Crohn's disease result in worsened quality of life and worse outcomes, evidence-based treatments do not currently exist due to lack of mechanistic understanding of this condition. The gut microbiome, which are the microbes that live in our gut, have been suggested as a potential cause of persistent symptoms. Diet is a major influence on the microbiome and may have a modifiable impact on persistent symptoms in Crohn's disease. However, this has not been well established.

The investigators propose a study period of approximately 8 weeks to evaluate the effects of a low sulfur diet in Crohn's disease. Participants will have an initial phone visit to determine eligibility to participate in the study and to review potential participants normal diet with a study nutritionist.

The treatment phase of 8 weeks will begin at the baseline visit (week 0). Participants will be randomized to receive a low sulfur diet or usual diet for 8 weeks. Participants on the low sulfur diet will meet with the study nutritionist to receive educational materials and recipes for the low sulfur diet. During this visit, participants will undergo testing, including a rectal barostat test to evaluate rectal sensation, glucose hydrogen breath test to assess for small intestinal bacterial overgrowth, lactulose-mannitol test to evaluate intestinal permeability, and a 24-hour urine sample to measure urine sulfate levels. Participants will be asked to collect saliva, serum, and stool samples.

Participants will then have phone visits every 2 weeks (week 2, week, 4, and week 6). Study nutritionists will monitor their dietary history and answer questions about the low sulfur diet if applicable.

At the conclusion of the 8 weeks, participants will have a final in-person study visit where rectal barostat, glucose hydrogen breath test, lactulose mannitol testing, and 24-hour urine sulfate level will be repeated. Stool and serum samples will be collected by participants.

Optional Low Sulfur Diet for participants randomized to the usual diet:

At the conclusion of the study (week 8), if participants randomized to usual diet are interested, will be offered treatment with a low sulfur diet for the next 8 weeks. Participants will meet with the study nutritionist that will provide educational materials on a low sulfur diet. Participants will have phone visits every 2 weeks (week 10, week 12, and week 14) to review dietary history and answer questions about the low sulfur diet. At the conclusion of the 16 weeks, participants will have a final in-person study visit where they will undergo testing, including a rectal barostat test to evaluate rectal sensation, glucose hydrogen breath test to assess for small intestinal bacterial overgrowth, lactulose-mannitol test to evaluate intestinal permeability, and a 24-hour urine sample to measure urine sulfate levels. Participants will be asked to collect saliva, serum, and stool samples.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Allen Lee, MD, MS; Phone Number: 734-936-9454; Email: allenlee@umich.edu
• Study Contact Backup: Name: Michael Santiago-Castro; Email: santiamn@med.umich.edu

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan
      • Principal Investigator: Allen Lee, MD
      • Contact: Allen Lee, MD, MS; Phone Number: 734-936-9454; Email: allenlee@umich.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Prior diagnosis of Crohn's disease based on endoscopic, radiographic, and/or histologic findings
• Quiescent Crohn's disease as defined by fecal calprotectin level less than 150 micrograms/gram (mcg/g) stool and/or absence of inflammation on colonoscopy within 30 and 90 days, respectively, of enrollment
• Persistent symptoms will be defined by abdominal pain and/or diarrhea T-scores greater than or equal to 55 by the National Institutes of Health (NIH) Patient-Reported outcomes measurement information system Gastrointestinal scale (PROMIS-GI)

Exclusion Criteria:

• Prior total colectomy
• Presence of an end ileostomy or colostomy in place
• Changes in immunosuppressive medications within the past 4 weeks
• Use of antibiotics or probiotics within the past 4 weeks
• Active or suspected stricture/stenosis of the GI tract
• Habitual vegetarian or vegan diet
• Active or suspected gastrointestinal stricture or stenosis
• Unable or unwilling to follow a low sulfur diet
• Patients who are underweight as defined by BMI < 18.5 kg/m2 or have significant unintentional weight loss as defined by >7.5% body weight in the past 3 months
• Currently pregnant, breastfeeding, and/or unwillingness/inability to use contraception start of the study until the last 13C-mannitol:lactulose test is complete. Sexually active male participants and/or their female partners of reproductive potential must agree to use effective contraception from the start of the study and until the last 13C-mannitol:lactulose test is complete. Women who are breastfeeding must stop breastfeeding during and for at least 12 hours after consuming the 13C-mannitol:lactulose test. Breastfeeding women must pump and dispose of the breastmilk during this time period
• Subjects must agree to not donate sperm or ova (eggs) or breast milk from the start of the study until the last 13C-mannitol:lactulose test is complete.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low Sulfur Diet; Participants in this group will follow a low sulfur diet. This diet decreases the amount of animal products (including meat, dairy, and eggs) as well as sulfur additives in the diet. The main types of foods in the low sulfur diet include fruits, vegetables, whole grains, nuts, seeds, and soy products.	Other: Low Sulfur Diet; Subjects will be placed on a low sulfur diet for 8 weeks with the support of a nutritionist. In addition, participants will be asked to complete: surveys, lactulose-mannitol test, glucose hydrogen breath test, blood samples, visceral sensation test, 24-hour urine sample for sulfate level, provide stool samples, optional colonoscopy.
Active Comparator: Usual Diet; Participants in this group will follow a standard of care usual diet for 8 weeks.	Other: Usual Diet; Subjects will continue on their usual diet for 8 weeks. At the end of 8 weeks, if participants are interested, they will be offered treatment with low sulfur diet for 8 weeks with the support of a nutritionist. In addition, participants will be asked to complete: surveys, lactulose-mannitol test, glucose hydrogen breath test, blood samples, visceral sensation test, 24-hour urine sample for sulfate level, provide stool samples, optional colonoscopy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in 24 hour urinary sulfate	Change in 24 hour urinary sulfate level from baseline	8 weeks
Change in 24 hour urinary sulfate	Change in 24 hour urinary sulfate level from baseline. This is for the group that voluntarily goes on the low sulfur diet after standard of care arm is completed	Approximately 16 weeks
Dietary Protein Intake for both groups as assessed by 24 hour diet recall	Dietary protein intake (animal-based) as assessed by 24 hour diet recall	8 weeks
Dietary Protein Intake as assessed by 24 hour diet recall	Dietary protein intake (animal-based) as assessed by 24 hour diet recall. This is for the group that voluntarily goes on the low sulfur diet after standard of care arm is completed.	Approximately 16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerability of Low Sulfur Diet based on the Visual Analog Scale (VAS)	The VAS has 5 questions in which participants are asked about knowledge, purchase, preparation, ease of following the diet, and overall tolerability of the sulfur diet. Each question participants will score between 0-100 (higher score is more tolerable with total points of 500).	Week 4
Tolerability of Low Sulfur Diet based on the Visual Analog Scale (VAS)	The VAS has 5 questions in which participants are asked about knowledge, purchase, preparation, ease of following the diet, and overall tolerability of the sulfur diet. Each question participants will score between 0-100 (higher score is more tolerable with total points of 500). This is for the group that voluntarily goes on the low sulfur diet after standard of care arm is completed.	Approximately week 12
Tolerability of Low Sulfur Diet based on the Visual Analog Scale (VAS)	The VAS has 5 questions in which participants are asked about knowledge, purchase, preparation, ease of following the diet, and overall tolerability of the sulfur diet. Each question participants will score between 0-100 (higher score is more tolerable with total points of 500).	Week 8
Tolerability of Low Sulfur Diet based on the Visual Analog Scale (VAS)	The VAS has 5 questions in which participants are asked about knowledge, purchase, preparation, ease of following the diet, and overall tolerability of the sulfur diet. Each question participants will score between 0-100 (higher score is more tolerable with total points of 500). This is for the group that voluntarily goes on the low sulfur diet after standard of care arm is completed.	Approximately 16 weeks

Collaborators and Investigators

• Sponsor: University of Michigan
• Investigators: Principal Investigator: Allen Lee, MD, MS, Assistant Professor

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2023
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: April 25, 2023
• First Submitted That Met QC Criteria: May 4, 2023
• First Posted (Actual): May 8, 2023

Study Record Updates

• Last Update Posted (Estimated): December 14, 2023
• Last Update Submitted That Met QC Criteria: December 12, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Microbiome; Crohn's disease; Quiescent Crohn's disease; Low sulfur diet
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: HUM00218796

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: To be determined

Drug and device information, study documents

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