Microbiome Modification to Enhance Stelara Response in Crohn's Disease (MIM-TESRIC)

This pilot study is being completed to determine whether a low-serine diet vs a high serine diet will reduce inflammation and symptoms in Crohn's disease (CD), as well as determine whether a low-serine diet (vs. a high serine diet) will improve responses in patients initiating therapy with Ustekinumab (Stelara), an FDA-approved biologic therapy for Crohn's disease.

Study Overview

• Status: Withdrawn
• Conditions: Crohn Disease
• Intervention / Treatment: Dietary supplement: Low serine diet; Dietary supplement: High serine diet

Detailed Description

Eligible participants that will be given Ustekinumab as part of their standard of care will be enrolled in this study.

The study hypotheses include that a low serine diet (compared to a high serine diet) in patients with active CD will:

• Reduce the relative abundance of Adherent invasive ecoli (AIEC), and increase the relative abundance of Bacteroides and Faecalibacterium in stool of patients with Crohn's disease.
• Make patients more likely to respond to ustekinumab (anti-Interleukin12/23) therapy with control of inflammation as measured by the mean Simple endoscopic subscore Crohn's disease (SES-CD) in each group at week 25.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Confirmed diagnosis of Crohn's Disease (CD) for at least 3 months prior to baseline. Appropriate documentation of biopsy results consistent with the diagnosis of CD, as determined by the investigator.
• Simple endoscopic subscore Crohn's disease (SES-CD) ≥ 7 for ileocolonic CD (or >=4 if only ileal CD) as confirmed by Dr. Higgins' scoring of colonoscopy.
• Are scheduled to begin Ustekinumab within the next 7-60 days
• Must be scheduled for clinically indicated colonoscopy, ordered by primary Gastroenterologist physician, and covered by insurance
• Must have access to a computer capable of completing video visits
• Must be willing to follow assigned meat-free diet provided by the study exclusively for 2 weeks
• Patients on anti-diarrheals must be on a stable dose for at least 2 weeks
• Prednisone is allowed up to a daily dose of 20 mg, with a stable dose for at least 1 week

Exclusion Criteria:

• Subject with a current diagnosis of Ulcerative Colitis
• Subjects requiring or receiving any Total Parenteral Nutrition (TPN) and/or exclusive enteral nutrition.
• Subjects who are pregnant or plan to become pregnant over the duration of the study
• Antibiotics in the previous 2 weeks.
• Probiotics in the previous 2 weeks.
• Ongoing therapy with infliximab, adalimumab, certolizumab, vedolizumab, or tofacitinib, is not allowed - must stop at least 1 week prior to ustekinumab start.
• Changes in dose of 5-aminosalicylates within the past 1 week - must be on a stable dose for at least one week.
• Changes in dose of immunomodulators (including Azathioprine, 6-mercaptopurine, methotrexate) within the past 4 weeks - must be on a stable dose for 4 weeks.
• Subjects with the following known complications of CD; Toxic megacolon, Short bowel syndrome or short gut (less than 100 centimeters, Ostomy, Symptomatic bowel strictures (scope cannot be passed through), any diagnosis that could interfere with nutrient absorption, note that actively draining fistulas are allowed at entry.
• Diabetes
• Subjects who use dietary supplements such as liquid or powder protein drinks/shakes, meal replacement shakes, and fiber supplements, etc. must be willing to stop at least 24 hours prior to starting the assigned diet
• Known allergy to soy products
• Oral Iron must be stopped at least 24 hours prior to baseline
• For severe anemia, intravenous (IV) iron can replace oral iron if approved and ordered by the prescribing physician
• Any subject currently hospitalized
• Any subject with a positive Clostridium difficile test (within 30 days of baseline) or currently being treated for Clostridium difficile.
• History of clinically significant medical condition or any other reason which, in the opinion of the PI, would interfere with the subject's participation
• Any active, chronic or recurrent infection that, based on the investigator's clinical assessment, makes the subject an unsuitable candidate for the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low serine diet	Dietary supplement: Low serine diet; Participants will be on this diet 1 week prior to initiation and 1 week after initiation of Ustekinumab (standard of care medication). The meals will be prepared in the Michigan Clinical Research Unit (MCRU) at the University of Michigan Health System and given to the participants.
Experimental: High serine diet	Dietary supplement: High serine diet; Participants will be on this diet 1 week prior to initiation and 1 week after initiation of Ustekinumab (standard of care medication). The meals will be prepared in the Michigan Clinical Research Unit (MCRU) at the University of Michigan Health System and given to the participants.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The mean simple endoscopic subscore Crohn's disease (SES-CD) score at week 25 between the two treatment groups.	This will be calculated by endoscopist at week 25.	25 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The mean Crohn's disease patient report outcomes (CD-PRO) score at week 2 will be compared between the two groups with Student's t test	There are a series of 52 questions to measure the extent of participant's crohn's disease. The higher the score the worse the disease.	2 weeks
The mean CD-PRO scores calculated by study team at week 25 will be compared between the two groups with Student's t test.	There are a series of 52 questions to measure the extent of participant's crohn's disease. The higher the score the worse the disease.	25 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The mean stool flagellin content at week 2 will be compared between the two groups with Student's t test.	This will be based on biopsies taken at 2 weeks.	2 weeks
The mean lamina propria mucosa (LPM) response in stool at week 2 will be compared between the two groups with Student's t test.	This will be based on biopsies taken at 2 weeks.	2 weeks
The mean C-reactive protein (CRP) at week 2 will be compared between the two groups with Student's t test.	Blood test checked at 2 weeks	2 weeks
The mean Fecal Calprotectin (FCP) at week 2 will be compared between the two groups with Student's t test.	Stool test checked at week 2	2 weeks
The mean lactulose to mannitol ratio (L/M) at week 2 will be compared between the two groups with Student's t test.	Urine test checked at week 2	2 weeks
The mean CRP at week 25 will be compared between the two groups with Student's t test.	Blood test checked at week 25	25 weeks
The mean FCP at week 25 will be compared between the two groups with Student's t test.	Stool test checked at week 25	25 weeks
The mean L/M ratio at week 25 will be compared between the two groups with Student's t test.	Urine test checked at week 25	25 weeks
The mean Crohn's Disease Activity Index (CDAI) scores calculated by study team at week 25 will be compared between the two groups with Student's t test	This score is based on blood tests, weight, and extra intestinal manifestations. The higher the score the worse the disease.	2 weeks

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: Kenneth Rainin Foundation
• Investigators: Principal Investigator: Peter D Higgins, MD, University of Michigan

Study record dates

Study Major Dates

• Study Start (Estimated): March 18, 2021
• Primary Completion (Estimated): March 1, 2023
• Study Completion (Estimated): March 1, 2023

Study Registration Dates

• First Submitted: March 9, 2021
• First Submitted That Met QC Criteria: March 9, 2021
• First Posted (Actual): March 12, 2021

Study Record Updates

• Last Update Posted (Actual): June 12, 2023
• Last Update Submitted That Met QC Criteria: June 9, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Diet; Ustekinumab; Stelara; Crohn's
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: HUM00185677

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