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

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

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.

Study Overview

• Status: Completed
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: Tofacitinib; Other: Fast Mimicking Diet; Drug: Infliximab induction; Drug: Ustekinumab induction

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Gabriella Grau, BS; Phone Number: 305-243-6405; Email: g.grau@miami.edu

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • The University of Miami

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients with ulcerative colitis who are beginning tofacitinib therapy.
2. Patients with ulcerative colitis who are initiating second line biologic therapy with ustekinumab
3. Patients with ulcerative colitis who are initiating second line biologic therapy with infliximab
4. Patients aged 18 years or older.
5. Patients with active disease defined as simple clinical colitis activity index (SCCAI) >2
6. Patients who have not been on antibiotics for 2 weeks or probiotics.

Exclusion Criteria:

1. Patients younger than 18 years.
2. Patients that do not meet the inclusion criteria specified above.
3. Patients with clinical signs of fulminant colitis, toxic megacolon, ischemic colitis or impending hospitalization for severe ulcerative colitis.
4. Patients with concomitant infectious colitis.
5. Patients allergic nuts/soy/sesame/oats.
6. Patients who do not like the food items that form part of the kits for the fasting mimicking diet (see below).
7. Patients that are diabetics on a glucose lowering drug.
8. Individuals with a history of syncope/presyncope with fasting or from medical conditions.
9. Women who are pregnant or nursing.
10. Individuals with very low BMI< or equal to 18.
11. Patients with the following comorbidities: chronic kidney disease, diabetes, active cancer.
12. Prohibited concomitant therapies will include TNF antagonists, azathioprine, methotrexate, and mercaptopurine.
13. Patients who routinely have fasting eating habits

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tofacitinib plus FMD group; 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; 10mg tofacitinib tablets taken twice daily for eight weeks; Other: Fast Mimicking Diet; 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.
Active Comparator: Tofacitinib only group; Participants in this group with UC consuming a standard, regular low-fiber diet will be provided Tofacitinib for eight consecutive weeks.	Drug: Tofacitinib; 10mg tofacitinib tablets taken twice daily for eight weeks
Experimental: Infliximab plus FMD group; 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; 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.; Drug: Infliximab induction; Participant will be initiated with infliximab induction therapy as second line biologic therapy
Active Comparator: Infliximab only; 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; Participant will be initiated with infliximab induction therapy as second line biologic therapy
Experimental: Ustekinumab plus FMD group; 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; 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.; Drug: Ustekinumab induction; Participant will be initiated with ustekinumab induction therapy as second line biologic therapy
Active Comparator: Ustekinumab only; 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; Participant will be initiated with ustekinumab induction therapy as second line biologic therapy

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Miami
• Collaborators: Pfizer
• Investigators: Principal Investigator: Oriana Damas, MD, University of Miami

Study record dates

Study Major Dates

• Study Start (Actual): September 18, 2020
• Primary Completion (Actual): December 7, 2023
• Study Completion (Actual): December 7, 2023

Study Registration Dates

• First Submitted: August 5, 2020
• First Submitted That Met QC Criteria: August 5, 2020
• First Posted (Actual): August 10, 2020

Study Record Updates

• Last Update Posted (Actual): December 8, 2023
• Last Update Submitted That Met QC Criteria: December 7, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Gastrointestinal Agents; Dermatologic Agents; Protein Kinase Inhibitors; Tumor Necrosis Factor Inhibitors; Janus Kinase Inhibitors; Infliximab; Tofacitinib; Ustekinumab
• Other Study ID Numbers: 20200436

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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No