Microbiome Modification to Enhance Stelara Response in Crohn's Disease (MIM-TESRIC)
Primary Purpose
Crohn Disease
Status
Withdrawn
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Low serine diet
High serine diet
Sponsored by
About this trial
This is an interventional treatment trial for Crohn Disease focused on measuring Ustekinumab, Stelara, Diet, Crohn's
Eligibility Criteria
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.
Sites / Locations
- University of Michigan
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Low serine diet
High serine diet
Arm Description
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
Full Information
NCT ID
NCT04795960
First Posted
March 9, 2021
Last Updated
June 9, 2023
Sponsor
University of Michigan
Collaborators
Kenneth Rainin Foundation
1. Study Identification
Unique Protocol Identification Number
NCT04795960
Brief Title
Microbiome Modification to Enhance Stelara Response in Crohn's Disease
Acronym
MIM-TESRIC
Official Title
Microbiome Modification to Enhance Stelara Response in Crohn's Disease
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Withdrawn
Why Stopped
Lack of eligible and interested patients
Study Start Date
March 18, 2021 (Anticipated)
Primary Completion Date
March 2023 (Anticipated)
Study Completion Date
March 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Michigan
Collaborators
Kenneth Rainin Foundation
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Crohn Disease
Keywords
Ustekinumab, Stelara, Diet, Crohn's
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Low serine diet
Arm Type
Experimental
Arm Title
High serine diet
Arm Type
Experimental
Intervention Type
Dietary Supplement
Intervention Name(s)
Low serine diet
Intervention Description
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.
Intervention Type
Dietary Supplement
Intervention Name(s)
High serine diet
Intervention Description
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.
Primary Outcome Measure Information:
Title
The mean simple endoscopic subscore Crohn's disease (SES-CD) score at week 25 between the two treatment groups.
Description
This will be calculated by endoscopist at week 25.
Time Frame
25 weeks
Secondary Outcome Measure Information:
Title
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
Description
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.
Time Frame
2 weeks
Title
The mean CD-PRO scores calculated by study team at week 25 will be compared between the two groups with Student's t test.
Description
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.
Time Frame
25 weeks
Other Pre-specified Outcome Measures:
Title
The mean stool flagellin content at week 2 will be compared between the two groups with Student's t test.
Description
This will be based on biopsies taken at 2 weeks.
Time Frame
2 weeks
Title
The mean lamina propria mucosa (LPM) response in stool at week 2 will be compared between the two groups with Student's t test.
Description
This will be based on biopsies taken at 2 weeks.
Time Frame
2 weeks
Title
The mean C-reactive protein (CRP) at week 2 will be compared between the two groups with Student's t test.
Description
Blood test checked at 2 weeks
Time Frame
2 weeks
Title
The mean Fecal Calprotectin (FCP) at week 2 will be compared between the two groups with Student's t test.
Description
Stool test checked at week 2
Time Frame
2 weeks
Title
The mean lactulose to mannitol ratio (L/M) at week 2 will be compared between the two groups with Student's t test.
Description
Urine test checked at week 2
Time Frame
2 weeks
Title
The mean CRP at week 25 will be compared between the two groups with Student's t test.
Description
Blood test checked at week 25
Time Frame
25 weeks
Title
The mean FCP at week 25 will be compared between the two groups with Student's t test.
Description
Stool test checked at week 25
Time Frame
25 weeks
Title
The mean L/M ratio at week 25 will be compared between the two groups with Student's t test.
Description
Urine test checked at week 25
Time Frame
25 weeks
Title
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
Description
This score is based on blood tests, weight, and extra intestinal manifestations. The higher the score the worse the disease.
Time Frame
2 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter D Higgins, MD
Organizational Affiliation
University of Michigan
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Microbiome Modification to Enhance Stelara Response in Crohn's Disease
We'll reach out to this number within 24 hrs