Crohn Disease
Conditions
Keywords
diet, specific carbohydrate diet, Mediterranean style diet, randomized controlled trial
Brief summary
This protocol is designed to compare the effectiveness of two dietary interventions for patients with Crohn's disease (CD): the Specific Carbohydrate Diet (SCD) and a Mediterranean style diet (MSD) that has been demonstrated to have numerous other health benefits. The two diets will be compared in terms of their ability to resolve both the symptoms and bowel inflammation that characterize this debilitating disease.
Detailed description
This study tested whether the SCD is superior to a MSD for managing symptoms and reducing inflammatory markers in patients with CD. The study was designed to include 194 patients with CD who have 1) active symptoms defined by a short Crohn's Disease Activity Index (sCDAI) score \>175. Although the initial plan was to also require that all patients have active inflammation documented by a fecal calprotectin (FCP) concentration \>250mcg/g or high sensitivity C-reactive protein (CRP) \>7 mg/L or ulceration of the small bowel and/or colon consistent with an SES-CD score \>4 as documented in routine clinical practice within 4 weeks of screening, a decision was made early in the recruitment period to enroll all patients with CD with sCDAI\>175 regardless of the results of the tests for inflammatory markers and to perform subgroup analyses of those with and without evidence of inflammation. Eligible participants were randomly assigned to follow one of the diets in a 1:1 ratio. Participants were provided with 3 meals and 2 snacks each day for a period of 6 weeks. The meals and snacks were prepared by the food vendor, Healthy Chef Creations, and were delivered directly to the participant's home once per week. Participants in both groups were also provided with instructions on how to follow the diets on their own. Participants reported their symptoms through an electronic diary and provided stool samples for FCP measurement and blood for CRP measurement at weeks 0, 6 and 12. The primary and secondary outcomes were assessed at week 6. Following week 6, participants were able to pay out of pocket to purchase food from Healthy Chef Creations and/or could attempt to follow their assigned diet completely on their own. At week 12, in addition to the primary and secondary outcomes assessed again
Interventions
OTHERDiet
food for the diet will be provided to the participants for 6 weeks and participants will follow the diet on their own for the remaining 6 weeks
Sponsors
Patient-Centered Outcomes Research Institute
Crohn's and Colitis Foundation
University of North Carolina, Chapel Hill
University of Pennsylvania
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 2. Documented diagnosis of Crohn's disease 3. sCDAI score \>175 4. Documentation of receipt of a baseline stool sample by the data coordinating center and hsCRP. 5. Access to a computer with internet and the ability to complete daily online surveys 6. Capable of providing consent to participate 7. Able to receive weekly food shipments delivered every Friday for 6 weeks
Exclusion criteria
1. Pregnancy 2. sCDAI \>400 3. Hospitalized patients 4. Anticipated need for surgery within 6 weeks of randomization 5. Use of the Specific Carbohydrate Diet within 4 weeks of screening 6. Start or change\*\*\* dose of thiopurines (azathioprine and 6-MP), methotrexate, natalizumab, or vedolizumab within 12 weeks prior to screening 7. Start or change\*\*\* dose of anti-tumor necrosis factor (TNF) agents (including infliximab (Remicade), adalimumab (Humira), certolizumab pegol (Cimzia), golimumab (Simponi) or ustekinumab within 8 weeks prior to screening. 8. Start or change in dose of any 5-aminosalicylic acid (5-ASA) medications within 2 weeks of screening. 9. Start or change dose of corticosteroids within 1 week of screening or a dose \>20mg/day prednisone or equivalent\* 10. Use of antibiotics (other than topical formulations) for any reason within 2 weeks prior to screening 11. Known symptomatic intestinal stricture. 12. Presence of an ostomy 13. Baseline stool frequency \>4 bowel movements/day when well 14. BMI \<16 15. BMI ≥40 16. Celiac disease 17. Documented C difficile colitis within four weeks of screening 18. Diabetes Mellitus requiring medication 19. Albumin\<2.0mg/dl, within 4 weeks of screening (if tested as part of routine clinical care) 20. Known allergy to tree nuts or peanuts 21. Other conditions that would be a contraindication to any of the study diets or preclude the participant from completing the study. 22. Currently participating in another clinical trial of a drug to treat Inflammatory Bowel Disease (IBD) or a dietary therapy for any indication. * Patients may continue these medications at stable dose for the first six weeks and budesonide may be used at any dose. After the 6th week in the study, patients may taper their steroid dose. The study will provide a recommended taper schedule. * Loading/induction doses of biologic type medication will be considered a stable doses. \*\*\*Exception for treatment failures: if a subject is determined to fail on any of the following standard lines of treatment at the treating investigator's discretion, subjects may screen for study intervention based upon the following wash out periods: 4 weeks for thiopurine and methotrexate and 8 weeks for natalizumab, vedolizumab, anti-TNF, or ustekinumab.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants That Achieved Symptomatic Remission at Week 6 | 6 weeks | Assessed by Short Crohn's Disease Activity Index (sCDAI) - diarrhea, abdominal pain and general well being; sCDAI \<150 in the absence of initiation or increase of any CD medications |
| Reduction in Bowel Inflammation Among Those Whose Screening Fecal Calprotectin (FC) Was Greater Than 250μg/g at Baseline and Who Had an FC Results at Both Baseline and Week 6 | 6 weeks | reduction of calprotectin to less than 250 μg/g and by greater than 50% from screening among those with screening FC \>250 μg/g |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants That Reached Clinical Remission at Week 6 | 6 weeks | Assessed by the CDAI - CDAI \<150 |
| Percentage of Participants With a Reduction in Systemic Inflammation at Week 6 | 6 weeks | reduction in high-sensitivity CRP (hsCRP) to \<5 mg/L and \>50% reduction from screening among those with screening hsCRP \>5mg/L |
Countries
United States
Participant flow
Recruitment details
The study was conducted in 33 clinical sites across the United States. Enrollment in the trial occurred between September 29, 2017 and October 8, 2019.
Pre-assignment details
There were 3 main reasons that participants who consented to the study were not randomized. The majority did not meet eligibility criteria. A small number withdrew or were lost to follow-up
Participants by arm
| Arm | Count |
|---|---|
| Mediterranean Style Diet Diet: food for the diet will be provided to the participants for 6 weeks and participants will follow the diet on their own for the remaining 6 weeks | 92 |
| Specific Carbohydrate Diet Diet: food for the diet will be provided to the participants for 6 weeks and participants will follow the diet on their own for the remaining 6 weeks | 99 |
| Total | 191 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Baseline to Week 6 | Adverse Event | 6 | 6 |
| Baseline to Week 6 | Change in Crohn's disease medication | 4 | 2 |
| Baseline to Week 6 | Difficulty following the diet | 0 | 2 |
| Baseline to Week 6 | Lost to Follow-up | 3 | 2 |
| Baseline to Week 6 | Physician Decision | 1 | 0 |
| Baseline to Week 6 | Withdrawal by Subject | 4 | 3 |
| Week 6 to Week 12 | Adverse Event | 4 | 3 |
| Week 6 to Week 12 | Change in medication | 5 | 7 |
| Week 6 to Week 12 | Difficulty following the assigned diet | 2 | 3 |
| Week 6 to Week 12 | Withdrawal by Subject | 9 | 4 |
Baseline characteristics
| Characteristic | Specific Carbohydrate Diet | Total | Mediterranean Style Diet |
|---|---|---|---|
| Age, Continuous | 36.0 years | 37 years | 37.0 years |
| AMeD Score | 2.0 units on a scale | 3.0 units on a scale | 3.0 units on a scale |
| Body Mass Index (BMI) | 25.6 kg/m2 | 25.3 kg/m2 | 25.1 kg/m2 |
| CDAI (median, Q1-Q3) | 210.0 units on a scale | 209.5 units on a scale | 206.8 units on a scale |
| CD behavior Non-stricturing, nonpenetrating | 60 Participants | 116 Participants | 56 Participants |
| CD behavior Penetrating | 13 Participants | 22 Participants | 9 Participants |
| CD behavior Stricturing | 17 Participants | 36 Participants | 19 Participants |
| CD behavior Stricturing and penetrating | 9 Participants | 17 Participants | 8 Participants |
| Crohn's disease distribution Colon alone | 13 Participants | 30 Participants | 17 Participants |
| Crohn's disease distribution Ileum alone | 30 Participants | 52 Participants | 22 Participants |
| Crohn's disease distribution Ileum and Colon | 55 Participants | 108 Participants | 53 Participants |
| Crohn's disease distribution Missing | 1 Participants | 1 Participants | 0 Participants |
| Current use of any biologic | 53 Participants | 108 Participants | 55 Participants |
| Current use of immunomodulators | 11 Participants | 22 Participants | 11 Participants |
| Current use of oral 5-ASA | 15 Participants | 21 Participants | 6 Participants |
| Current use of oral steroids | 11 Participants | 14 Participants | 3 Participants |
| Current use of rectal 5 ASA | 3 Participants | 3 Participants | 0 Participants |
| Current use of rectal steroids | 2 Participants | 3 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 8 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 92 Participants | 180 Participants | 88 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 3 Participants | 0 Participants |
| FC>250 ug/g or hsCRP>5 mg/L or definite inflammation on colonoscopy | 50 Participants | 88 Participants | 38 Participants |
| fecal calprotectin (FC) >250 ug/g | 23 Participants | 36 Participants | 13 Participants |
| fecal calprotectin (FC) ug/g | 107.5 ug/g | 70 ug/g | 40.0 ug/g |
| History of intestinal surgery | 29 Participants | 63 Participants | 34 Participants |
| History of perianal fistula | 20 Participants | 44 Participants | 24 Participants |
| hsCRP >5 mg/L | 37 Participants | 65 Participants | 28 Participants |
| hsCRP mg/L | 3.2 mg/L | 2.9 mg/L | 2.5 mg/L |
| Inflammation on colonoscopy No | 1 Participants | 3 Participants | 2 Participants |
| Inflammation on colonoscopy Not performed | 89 Participants | 169 Participants | 80 Participants |
| Inflammation on colonoscopy Probably | 0 Participants | 1 Participants | 1 Participants |
| Inflammation on colonoscopy Probably not | 1 Participants | 2 Participants | 1 Participants |
| Inflammation on colonoscopy Yes | 8 Participants | 16 Participants | 8 Participants |
| Inflammatory back pain screen 0 | 40 Participants | 70 Participants | 30 Participants |
| Inflammatory back pain screen 1-3 | 40 Participants | 79 Participants | 39 Participants |
| Inflammatory back pain screen >3 | 18 Participants | 40 Participants | 22 Participants |
| Inflammatory back pain screen Missing | 1 Participants | 2 Participants | 1 Participants |
| Number of prior anti-TNF medications 0 | 34 Participants | 62 Participants | 28 Participants |
| Number of prior anti-TNF medications 1 | 29 Participants | 51 Participants | 22 Participants |
| Number of prior anti-TNF medications 2 | 26 Participants | 58 Participants | 32 Participants |
| Number of prior anti-TNF medications 3 | 9 Participants | 18 Participants | 9 Participants |
| Number of prior anti-TNF medications 4 | 1 Participants | 2 Participants | 1 Participants |
| Prior ustekinumab | 23 Participants | 45 Participants | 22 Participants |
| Prior vedolizumab | 22 Participants | 49 Participants | 27 Participants |
| PROMIS measures (median, Q1-Q3) Fatigue | 58.9 units on a scale | 59.6 units on a scale | 60.4 units on a scale |
| PROMIS measures (median, Q1-Q3) Pain interference | 61.3 units on a scale | 61.2 units on a scale | 60.1 units on a scale |
| PROMIS measures (median, Q1-Q3) Sleep disturbance | 54.5 units on a scale | 56.0 units on a scale | 57.3 units on a scale |
| PROMIS measures (median, Q1-Q3) Social isolation | 47.2 units on a scale | 47.9 units on a scale | 48.4 units on a scale |
| Race/Ethnicity, Customized Asian | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Black | 5 Participants | 7 Participants | 2 Participants |
| Race/Ethnicity, Customized Multiracial | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 4 Participants | 3 Participants |
| Race/Ethnicity, Customized Unknown | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 88 Participants | 174 Participants | 86 Participants |
| sCDAI (median, Q1-Q3) | 226.0 units on a scale | 223.0 units on a scale | 217.7 units on a scale |
| Sex: Female, Male Female | 58 Participants | 121 Participants | 63 Participants |
| Sex: Female, Male Male | 41 Participants | 70 Participants | 29 Participants |
| Short IBDQ (median, Q1-Q3) | 40.0 units on a scale | 39.0 units on a scale | 38.0 units on a scale |
| Smoking status Current | 0 Participants | 3 Participants | 3 Participants |
| Smoking status Never | 79 Participants | 147 Participants | 68 Participants |
| Smoking status Past | 20 Participants | 41 Participants | 21 Participants |
| Years since CD diagnosis | 10 years | 10 years | 10 years |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 92 | 0 / 99 |
| other Total, other adverse events | 18 / 92 | 19 / 99 |
| serious Total, serious adverse events | 5 / 92 | 3 / 99 |
Outcome results
Primary
Percentage of Participants That Achieved Symptomatic Remission at Week 6
Assessed by Short Crohn's Disease Activity Index (sCDAI) - diarrhea, abdominal pain and general well being; sCDAI \<150 in the absence of initiation or increase of any CD medications
Time frame: 6 weeks
Population: percentage of participants who achieved symptomatic remission at week 6
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mediterranean Style Diet | Percentage of Participants That Achieved Symptomatic Remission at Week 6 | 40 Participants |
| Specific Carbohydrate Diet | Percentage of Participants That Achieved Symptomatic Remission at Week 6 | 46 Participants |
Primary
Reduction in Bowel Inflammation Among Those Whose Screening Fecal Calprotectin (FC) Was Greater Than 250μg/g at Baseline and Who Had an FC Results at Both Baseline and Week 6
reduction of calprotectin to less than 250 μg/g and by greater than 50% from screening among those with screening FC \>250 μg/g
Time frame: 6 weeks
Population: This measure includes only those whose screening fecal calprotectin (FC) was greater than 250μg/g at baseline and who had an FC results at both baseline and week 6
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mediterranean Style Diet | Reduction in Bowel Inflammation Among Those Whose Screening Fecal Calprotectin (FC) Was Greater Than 250μg/g at Baseline and Who Had an FC Results at Both Baseline and Week 6 | 4 Participants |
| Specific Carbohydrate Diet | Reduction in Bowel Inflammation Among Those Whose Screening Fecal Calprotectin (FC) Was Greater Than 250μg/g at Baseline and Who Had an FC Results at Both Baseline and Week 6 | 8 Participants |
Secondary
Percentage of Participants That Reached Clinical Remission at Week 6
Assessed by the CDAI - CDAI \<150
Time frame: 6 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mediterranean Style Diet | Percentage of Participants That Reached Clinical Remission at Week 6 | 44 Participants |
| Specific Carbohydrate Diet | Percentage of Participants That Reached Clinical Remission at Week 6 | 48 Participants |
Secondary
Percentage of Participants With a Reduction in Systemic Inflammation at Week 6
reduction in high-sensitivity CRP (hsCRP) to \<5 mg/L and \>50% reduction from screening among those with screening hsCRP \>5mg/L
Time frame: 6 weeks
Population: This measure includes only those that had a screening hsCRP \> 5mg/L and had hsCRP measured at both screening and at week 6
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mediterranean Style Diet | Percentage of Participants With a Reduction in Systemic Inflammation at Week 6 | 1 Participants |
| Specific Carbohydrate Diet | Percentage of Participants With a Reduction in Systemic Inflammation at Week 6 | 2 Participants |