Second Line Induction Therapy and Healthy Diet for Patients With Ulcerative Colitis

Study Overview
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Brief Summary
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The purpose of this study is to determine whether a diet intervention (the Fasting Mimicking diet) will help induce clinical and biochemical response to tofacitinib therapy or second line biologic therapy with ustekinumab or infliximab in patients with ulcerative colitis. Study period will be 8 weeks during induction of tofacitinib or ustekinumab or infliximab. The primary aims of this study are to determine clinical response and improvement in fecal calprotectin and C-reactive protein levels. Secondary outcomes will include assessment of changes in the stool microbiome.

Official Title
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A Randomized Control Study to Examine the Influence of a Healthy Diet on Moderate to Severe Ulcerative Colitis Patients Undergoing Second Line Induction With Biological Medications Tofacitinib, Ustekinumab or Vedolizumab

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: Tofacitinib
* Other: Fast Mimicking Diet
* Drug: Ustekinumab induction
* Drug: Infliximab induction


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with ulcerative colitis who are beginning tofacitinib therapy. Patients with ulcerative colitis who are initiating second line biologic therapy with ustekinumab Patients with ulcerative colitis who are initiating second line biologic therapy with infliximab Patients aged 18 years or older. Patients with active disease defined as simple clinical colitis activity index (SCCAI) >2 Patients who have not been on antibiotics for 2 weeks or probiotics. Exclusion Criteria: Patients younger than 18 years. Patients that do not meet the inclusion criteria specified above. Patients with clinical signs of fulminant colitis, toxic megacolon, ischemic colitis or impending hospitalization for severe ulcerative colitis. Patients with concomitant infectious colitis. Patients allergic nuts/soy/sesame/oats. Patients who do not like the food items that form part of the kits for the fasting mimicking diet (see below). Patients that are diabetics on a glucose lowering drug. Individuals with a history of syncope/presyncope with fasting or from medical conditions. Women who are pregnant or nursing. Individuals with very low BMI< or equal to 18. Patients with the following comorbidities: chronic kidney disease, diabetes, active cancer. Prohibited concomitant therapies will include TNF antagonists, azathioprine, methotrexate, and mercaptopurine. Patients who routinely have fasting eating habits

Ages Eligible for Study
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Minimum Age: 18 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: Tofacitinib plus FMD group<br>Participants in this group with UC consuming a standard, regular low-fiber diet will be provided Tofacitinib for eight consecutive weeks with the addition of two, five-day cycles of Fast Mimicking Diet (FMD) daily meals on weeks 2 and 6. | Drug: Tofacitinib<br>* 10mg tofacitinib tablets taken twice daily for eight weeks<br>Other: Fast Mimicking Diet<br>* FMD is a five day meal plan that includes foods such as soups, snacks, bards, teas and supplements (omega-3 fatty acids) for a total of 66 items per box. The diet is plant-based, gluten free and dairy free without any artificial preservatives, chemicals or biologically active ingredients.<br>|
| Active Comparator: Tofacitinib only group<br>Participants in this group with UC consuming a standard, regular low-fiber diet will be provided Tofacitinib for eight consecutive weeks. | Drug: Tofacitinib<br>* 10mg tofacitinib tablets taken twice daily for eight weeks<br>|
| Experimental: Infliximab plus FMD group<br>Participants in this group with UC consuming a standard, regular low-fiber diet and will have initiated second line biologic therapy with infliximab with the addition of two, five-day cycles of Fast Mimicking Diet (FMD) daily meals on weeks 2 and 6. | Other: Fast Mimicking Diet<br>* FMD is a five day meal plan that includes foods such as soups, snacks, bards, teas and supplements (omega-3 fatty acids) for a total of 66 items per box. The diet is plant-based, gluten free and dairy free without any artificial preservatives, chemicals or biologically active ingredients.<br>Drug: Infliximab induction<br>* Participant will be initiated with infliximab induction therapy as second line biologic therapy<br>|
| Active Comparator: Infliximab only<br>Participants in this group with UC consuming a standard, regular low-fiber diet for 8 consecutive weeks and will have initiated second line biologic therapy with infliximab | Drug: Infliximab induction<br>* Participant will be initiated with infliximab induction therapy as second line biologic therapy<br>|
| Experimental: Ustekinumab plus FMD group<br>Participants in this group with UC consuming a standard, regular low-fiber diet and will have initiated second line biologic therapy with ustekinumab with the addition of two, five-day cycles of Fast Mimicking Diet (FMD) daily meals on weeks 2 and 6. | Other: Fast Mimicking Diet<br>* FMD is a five day meal plan that includes foods such as soups, snacks, bards, teas and supplements (omega-3 fatty acids) for a total of 66 items per box. The diet is plant-based, gluten free and dairy free without any artificial preservatives, chemicals or biologically active ingredients.<br>Drug: Ustekinumab induction<br>* Participant will be initiated with ustekinumab induction therapy as second line biologic therapy<br>|
| Active Comparator: Ustekinumab only<br>Participants in this group with UC consuming a standard, regular low-fiber diet for 8 consecutive weeks and will have initiated second line biologic therapy with ustekinumab | Drug: Ustekinumab induction<br>* Participant will be initiated with ustekinumab induction therapy as second line biologic therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients who achieved clinical response | Clinical response will be evaluated using the Simple Clinical Colitis Activity Index (SCCAI). The SCCAI has a total range from 0-19 with a higher score indicating greater disease activity. A clinical response is defined as a SCCAI decrease of ≥2 points from baseline. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Fecal Calprotectin levels | Calprotectin levels will be evaluated using fecal samples | baseline, 8 weeks | 
| Change in CRP levels | C-Reactive Protein (CRP) levels will be evaluated using blood samples | baseline, 8 weeks |