Microbiome Modification to Enhance Stelara Response in Crohn's Disease

Study Overview
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Brief Summary
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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
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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.

Official Title
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Microbiome Modification to Enhance Stelara Response in Crohn's Disease

Conditions
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Crohn Disease

Intervention / Treatment
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* Dietary Supplement: Low serine diet
* Dietary Supplement: High serine diet


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low serine diet<br> | Dietary Supplement: Low serine diet<br>* 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.<br>|
| Experimental: High serine diet<br> | Dietary Supplement: High serine diet<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ustekinumab, Stelara, Diet, Crohn's