Ulcerative Colitis
Conditions
Brief summary
The purpose of this study is to determine whether a diet intervention (the Fasting Mimicking diet) will help induce clinical and biochemical response to an advanced therapy in patients with ulcerative colitis. Study period will be 8 weeks during induction of advanced therapies. The primary aims of this study will be clinical response, as determined by the simple clinical colitis activity index (SCCAI). Secondary outcomes will be improvement in fecal calprotectin and C-reactive protein levels.
Detailed description
Advanced therapies included will be: JAK inhibitors (tofacitinib or upadacitinib) IL-23 inhibitors (ustekinumab or risankizumab) Anti-TNF (infliximab) Patients will be provided these medications as part of their standard of care, as decided by their treating physician.
Interventions
OTHERA plant based high fiber diet that mimics fasting (FMD) plus advanced therapy
Patients will do two 5-day cycles of a fasting mimicking diet. They will start the first diet cycle 1 week after initiating a new advanced therapy: Tofacitinib and Upadacitinib (JAK inhibitors), Infliximab (anti-TNF), Ustekinumab or Risankizumab (IL-23 inhibitors).
DRUGAdvanced therapy only without dietary intervention
Patients in this group will start an advanced therapy and follow a diet solely based on dietary tolerance: new advanced therapy: Tofacitinib and Upadacitinib (JAK inhibitors), Infliximab (anti-TNF), Ustekinumab or Risankizumab (IL-23 inhibitors).
Sponsors
Pfizer
University of Miami
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Who Achieved Clinical Response | 8 weeks | 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 ≥3 points from baseline. Therefore, the study team will examine the percentage of patients who achieve 'clinical response', defined by an SCCAI decrease of ≥3 points. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fecal Calprotectin Levels Measured in Micrograms/Gram | baseline, 8 weeks | Calprotectin levels were evaluated using fecal samples to compare the levels between the treatment and control arms before (baseline) and after the intervention (at 8 weeks). Fecal calprotectin was measured using a BUHLMANN fCAL ELISA Kit. Unit of measure was micrograms/gram. |
| CRP Levels Measured in mg/dl | baseline, 8 weeks | Comparison of Median C-Reactive Protein (CRP) levels between the treatment and control arms before (baseline) and after the intervention (at 8 weeks) will be evaluated using blood samples, unit of measure was mg/dl |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Advanced Therapy Plus FMD Group Participants in this group with UC will start an advanced therapy for eight consecutive weeks with the addition of two, five-day cycles of Fast Mimicking Diet (FMD) daily meals on weeks 2 and 7.
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. | 14 |
| Advanced Therapy Only Group (no Diet Intervention) Participants in this group with UC will be begin an advanced therapy and consume a a diet based on dietary tolerance. | 18 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | abdominal pain after starting tofacitinib | 1 | 1 |
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | did not want to follow diet | 1 | 0 |
| Overall Study | flare up of ulcerative colitis | 0 | 1 |
| Overall Study | initiated another diet on their own | 0 | 2 |
| Overall Study | Lost to Follow-up | 0 | 2 |
Baseline characteristics
| Characteristic | Advanced Therapy Only Group (no Diet Intervention) | Total | Advanced Therapy Plus FMD Group |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 3 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants | 29 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 15 Participants | 25 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 7 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 9 Participants | 15 Participants | 6 Participants |
| Sex: Female, Male Male | 9 Participants | 17 Participants | 8 Participants |
| Simple clinical colitis activity index | 7.0 units on a scale | 7.5 units on a scale | 8.0 units on a scale |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 18 |
| other Total, other adverse events | 1 / 14 | 2 / 18 |
| serious Total, serious adverse events | 2 / 14 | 0 / 18 |
Outcome results
Primary
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 ≥3 points from baseline. Therefore, the study team will examine the percentage of patients who achieve 'clinical response', defined by an SCCAI decrease of ≥3 points.
Time frame: 8 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Advanced Therapy Plus FMD Group | Percentage of Patients Who Achieved Clinical Response | 57 percentage of patients |
| Advanced Therapy Without FMD (Medication Only Group) | Percentage of Patients Who Achieved Clinical Response | 35 percentage of patients |
p-value: 0.05Mixed Models Analysis
Secondary
CRP Levels Measured in mg/dl
Comparison of Median C-Reactive Protein (CRP) levels between the treatment and control arms before (baseline) and after the intervention (at 8 weeks) will be evaluated using blood samples, unit of measure was mg/dl
Time frame: baseline, 8 weeks
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Advanced Therapy Plus FMD Group | CRP Levels Measured in mg/dl | Baseline | 0.45 mg/dl |
| Advanced Therapy Plus FMD Group | CRP Levels Measured in mg/dl | Week 8 | 0.09 mg/dl |
| Advanced Therapy Without FMD (Medication Only Group) | CRP Levels Measured in mg/dl | Week 8 | 1.10 mg/dl |
| Advanced Therapy Without FMD (Medication Only Group) | CRP Levels Measured in mg/dl | Baseline | 2.10 mg/dl |
Secondary
Fecal Calprotectin Levels Measured in Micrograms/Gram
Calprotectin levels were evaluated using fecal samples to compare the levels between the treatment and control arms before (baseline) and after the intervention (at 8 weeks). Fecal calprotectin was measured using a BUHLMANN fCAL ELISA Kit. Unit of measure was micrograms/gram.
Time frame: baseline, 8 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Advanced Therapy Plus FMD Group | Fecal Calprotectin Levels Measured in Micrograms/Gram | Baseline | 3710 mcg/gram |
| Advanced Therapy Plus FMD Group | Fecal Calprotectin Levels Measured in Micrograms/Gram | Week 8 | 1375 mcg/gram |
| Advanced Therapy Without FMD (Medication Only Group) | Fecal Calprotectin Levels Measured in Micrograms/Gram | Baseline | 5138 mcg/gram |
| Advanced Therapy Without FMD (Medication Only Group) | Fecal Calprotectin Levels Measured in Micrograms/Gram | Week 8 | 5691 mcg/gram |