search
Back to results

Personalized Research on Diet in Ulcerative Colitis and Crohn's Disease (PRODUCE)

Primary Purpose

Inflammatory Bowel Diseases, Crohn Disease, Ulcerative Colitis

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Specific Carbohydrate Diet (SCD)
Modified Specific Carbohydrate Diet (MSCD)
Sponsored by
Children's Hospital Medical Center, Cincinnati
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Inflammatory Bowel Diseases

Eligibility Criteria

7 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Diagnosis of Crohn's Disease (CD) or ulcerative colitis (UC) or Indeterminate colitis (IC)
  • Age 7-18 years
  • Enrolled in the ImproveCareNow (ICN2) registry

  • Evidence of acute inflammation and/or elevated acute phase reactant as measured by Fecal calprotectin 1.5 times the upper limit of normal, Lactoferrin 1.5 times the upper limit of normal, CRP 1.15 times the upper limit of normal, or ESR 1.15 times the upper limit of normal (based on local reference ranges) obtained within 8 weeks of enrollment.

    • Potential participants who are close to meeting one of the acute inflammation and/or elevated acute phase reactant markers and who meet all other study criteria will be considered for study participation on a case by case basis by the investigative study team in consultation with the patient's primary gastroenterologist.

Exclusion Criteria:

Complex and Unstable IBD:

  • Currently or within the past 9 months has had an abscess, fistula, stricturing CD, or ostomy
  • Severe disease activity as measured by a short Pediatric Crohn's Disease Activity Index (SPCDAI) score of >45 or Pediatric Ulcerative Colitis Activity Index (PUCAI) score of >60 assessed within three weeks of enrollment
  • Ever had history of full colectomy
  • Hospitalization or surgery planned within 3 months
  • Ongoing active gastrointestinal infection
  • Severe Malnutrition (BMI less than 5th percentile)

  • Recent medication changes including:

    • Thiopurines, natalizumab, or methotrexate started within 8 weeks prior to enrollment
    • Anti TNF (infliximab, adalimumab) started within 8 weeks prior to enrollment
    • Vedolizumab started within 16 weeks prior to enrollment
    • Increase in corticosteroids within 4 weeks of screening or have dose >20 mg prednisone or equivalent

Evidence of Other Complicating Medical Issues:

  • Other serious medical conditions, such as neurological, liver, kidney, or systemic disease
  • Serious psychological or psychiatric conditions such as eating disorders or self-harm
  • Pregnancy
  • Tobacco, alcohol, or illicit drug abuse

Inability to Complete the Protocol

  • Non-English speaking participants

  • On SCD or modified SCD anytime within 8 weeks of enrollment

    • If an otherwise eligible patient is on SCD or modified SCD within 8 weeks of enrollment but they are noncompliant per the determination of the patient's dietitian/primary gastroenterologist, then this patient is eligible to participant in the study.
  • Participants on a vegan diet
  • Lack of smart phone and data plan for participating caregiver
  • Participating in another concurrent intervention study

Sites / Locations

  • Arkansas Children's Hospital
  • Children's Hospital of Los Angeles
  • UCSF Benioff Children's Hospital Oakland
  • Lucile Packard Children's Hospital
  • University of California San Francisco Benioff Children's Hospita;
  • Nemours, Alfred I duPont Hospital for Children
  • Nemours Children's Speciality Care
  • Nemours Children's Hospital
  • GI Care for Kids
  • Riley Hospital for Children
  • Massachusetts General Hospital
  • Children's Mercy Hospital
  • Levine Children's Hospital
  • Nationwide Children's Hospital
  • Oregon Health Sciences University
  • Dell Children's Medical Center of Central Texas
  • UT Soutwestern Medical Center
  • Pediatric Specialists of Virginia
  • Children's Hospital of the King's Daughters
  • Seattle Children's

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Specific Carbohydrate Diet (First)

Modified Specific Carbohydrate Diet (First)

Arm Description

Participants will be following the Specific Carbohydrate Diet (SCD). Allowed foods include meat/fish/poultry, eggs, some legumes (e.g., lentils and split peas are permitted, chickpeas and soybeans are not), fully fermented yogurt, non-starchy vegetables, ripe fruit, nuts/seeds, honey and nut flours (e.g. almond flour or coconut flour). Restricted foods include all grains, milk products aside from 24-hour fermented SCD yogurt and cheeses aged greater than 30 days, starchy vegetables, processed foods with food additives and sweeteners other than honey.

Participants will be following a modified Specific Carbohydrate Diet (MSCD). In addition to the foods in the SCD, allowed foods will expand to include organic rice, oats, sweet potatoes, grade A maple syrup and cocoa. Gluten, corn products, milk products (except yogurt and hard cheeses), sweeteners (except honey), and process foods are still restricted.

Outcomes

Primary Outcome Measures

Stool frequency
Self-reported number of stools per day entered as an integer in the study mobile app
Stool Consistency
Self-reported assessment of stool consistency using the Bristol Stool Scale entered in the study mobile app
Pain Interference
Patient reported outcome of pain interference measured using the Patient Reported Outcomes Measurement Information System (PROMIS) Pain Interference Scale on the study app. The scale includes 8 items and responses to each item are on a 0 (Never) to 4 (Almost Always) scale. Higher scores indicate greater pain interference. Look up tables provided by the PROMIS Assessment Center will be used to transform the raw score to a T-score such that 50 is the mean for the population with a standard deviation of 10.
Gastrointestinal Symptoms
Self-reported outcome of GI symptom burden measured using the PROMIS GI Symptoms scale on the study app. The scale includes 4 items and responses to each item are on a 1 (Never) to 5 (Almost Always) scale. Higher scores indicate greater GI symptom burden. Look up tables provided by the measure developers will be used to transform the raw score to a T-score such that 50 is the mean for the population with a standard deviation of 10.
Fecal Calprotectin
Laboratory measurement of intestinal inflammation. Stool will be collected by participants at home and will be mailed to a central lab for processing and analysis.

Secondary Outcome Measures

Provider measured disease activity
Pediatric Ulcerative Colitis Index (PUCAI) or Short Pediatric Crohn's Index (sPCDAI) are completed by care providers at all scheduled clinic visits as part of standard of care and are entered into the ImproveCareNow (ICN) registry.
Laboratory markers of disease activity and inflammation
C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), albumin, and hematocrit as collected as part of standard of care and are entered into the ImproveCareNow (ICN) registry.
Growth
Weight and height are collected at all clinic visits and at the dietitian study follow up visits (2 weeks into the first diet period of each diet). These data are entered into the ICN registry as part of regular data entry. We will calculate weight for age Z-scores for all entries during study period. The age-specific mean and standard deviation from U.S. population norms will be used to calculate Z-scores using the Centers for Disease Control Epi-Info program.
Short Crohn's Disease Activity Index (sCDAI)
The short Crohn's disease activity index (sCDAI) will be used to assess disease activity based on self-report via the study app. For the sCDAI, items assess general well-being, abdominal pain, and liquid stools. Respondents are asked to report on symptoms for the previous 24 hour period. Scores are calculated based on a published algorithm.
Pediatric Ulcerative Colitis Activity Index (PUCAI)
A self-reported version of the Pediatric Ulcerative Colitis Activity Index (PUCAI) will be used to assess disease activity based on self-report via the study app. For the PUCAI, respondents are asked to report on abdominal pain, bloody stools, stool consistency, stool frequency, nocturnal stools, and activity level over the prior 24-hours. A weighted, summed score is calculated with higher scores indicating worse disease (score range 0-85).

Full Information

First Posted
September 26, 2017
Last Updated
June 22, 2022
Sponsor
Children's Hospital Medical Center, Cincinnati
Collaborators
University of California, San Francisco, Seattle Children's Hospital, Dayton Children's Hospital, Brown University
search

1. Study Identification

Unique Protocol Identification Number
NCT03301311
Brief Title
Personalized Research on Diet in Ulcerative Colitis and Crohn's Disease
Acronym
PRODUCE
Official Title
Using Single Subject (N-of-1) Designs to Answer Patient-Identified Research Questions--Aim 1: Personalized Research on Diet in Ulcerative Colitis and Crohn's Disease
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Completed
Study Start Date
April 10, 2018 (Actual)
Primary Completion Date
September 8, 2020 (Actual)
Study Completion Date
September 8, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Hospital Medical Center, Cincinnati
Collaborators
University of California, San Francisco, Seattle Children's Hospital, Dayton Children's Hospital, Brown University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
A series of N-of-1 trials will be used to determine the effectiveness of a specific carbohydrate diet (SCD) versus a modified SCD in patients in reducing symptoms and inflammatory burden at both the individual and population level. This is a four-year study. The study staff will recruit up to 60 patients across up to 21 sites in patients aged 7-18 with mild to moderate disease activity.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Inflammatory Bowel Diseases, Crohn Disease, Ulcerative Colitis, Indeterminate Colitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Model Description
We are using a series of N-of-1 trials where patients alternate (cross) between the two study interventions at set intervals. N-of-1 trial results will be examined at the individual and population level (through meta-analysis of individual N-of-1 trials)
Masking
None (Open Label)
Allocation
Randomized
Enrollment
54 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Specific Carbohydrate Diet (First)
Arm Type
Experimental
Arm Description
Participants will be following the Specific Carbohydrate Diet (SCD). Allowed foods include meat/fish/poultry, eggs, some legumes (e.g., lentils and split peas are permitted, chickpeas and soybeans are not), fully fermented yogurt, non-starchy vegetables, ripe fruit, nuts/seeds, honey and nut flours (e.g. almond flour or coconut flour). Restricted foods include all grains, milk products aside from 24-hour fermented SCD yogurt and cheeses aged greater than 30 days, starchy vegetables, processed foods with food additives and sweeteners other than honey.
Arm Title
Modified Specific Carbohydrate Diet (First)
Arm Type
Experimental
Arm Description
Participants will be following a modified Specific Carbohydrate Diet (MSCD). In addition to the foods in the SCD, allowed foods will expand to include organic rice, oats, sweet potatoes, grade A maple syrup and cocoa. Gluten, corn products, milk products (except yogurt and hard cheeses), sweeteners (except honey), and process foods are still restricted.
Intervention Type
Other
Intervention Name(s)
Specific Carbohydrate Diet (SCD)
Intervention Description
Patients will be randomized to start with either a strict SCD or modified SCD. Participants will alternate between each diet in 8-week intervals for a total duration of approximately 34 weeks. Participants will complete two 8-week intervention periods on each diet.
Intervention Type
Other
Intervention Name(s)
Modified Specific Carbohydrate Diet (MSCD)
Intervention Description
Patients will be randomized to start with either a strict SCD or modified SCD. Participants will alternate between each diet in 8-week intervals for a total duration of approximately 34 weeks. Participants will complete two 8-week intervention periods on each diet.
Primary Outcome Measure Information:
Title
Stool frequency
Description
Self-reported number of stools per day entered as an integer in the study mobile app
Time Frame
Daily through study completion (34 weeks from randomization)
Title
Stool Consistency
Description
Self-reported assessment of stool consistency using the Bristol Stool Scale entered in the study mobile app
Time Frame
Daily through study completion (34 weeks from randomization)
Title
Pain Interference
Description
Patient reported outcome of pain interference measured using the Patient Reported Outcomes Measurement Information System (PROMIS) Pain Interference Scale on the study app. The scale includes 8 items and responses to each item are on a 0 (Never) to 4 (Almost Always) scale. Higher scores indicate greater pain interference. Look up tables provided by the PROMIS Assessment Center will be used to transform the raw score to a T-score such that 50 is the mean for the population with a standard deviation of 10.
Time Frame
Weekly through study completion (34 weeks from randomization)
Title
Gastrointestinal Symptoms
Description
Self-reported outcome of GI symptom burden measured using the PROMIS GI Symptoms scale on the study app. The scale includes 4 items and responses to each item are on a 1 (Never) to 5 (Almost Always) scale. Higher scores indicate greater GI symptom burden. Look up tables provided by the measure developers will be used to transform the raw score to a T-score such that 50 is the mean for the population with a standard deviation of 10.
Time Frame
Weekly through study completion (34 weeks from randomization)
Title
Fecal Calprotectin
Description
Laboratory measurement of intestinal inflammation. Stool will be collected by participants at home and will be mailed to a central lab for processing and analysis.
Time Frame
At baseline and once at the end of each treatment period (weeks 10, 18, 26 and 34) for a total of 5 times
Secondary Outcome Measure Information:
Title
Provider measured disease activity
Description
Pediatric Ulcerative Colitis Index (PUCAI) or Short Pediatric Crohn's Index (sPCDAI) are completed by care providers at all scheduled clinic visits as part of standard of care and are entered into the ImproveCareNow (ICN) registry.
Time Frame
At baseline, 10 weeks and up to 2 -4 more times as standard of care visits for the duration of the study (34 weeks from randomization)
Title
Laboratory markers of disease activity and inflammation
Description
C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), albumin, and hematocrit as collected as part of standard of care and are entered into the ImproveCareNow (ICN) registry.
Time Frame
At baseline, 10 weeks and up to 2 -4 more times as standard of care visits for the duration of the study (34 weeks from randomization)
Title
Growth
Description
Weight and height are collected at all clinic visits and at the dietitian study follow up visits (2 weeks into the first diet period of each diet). These data are entered into the ICN registry as part of regular data entry. We will calculate weight for age Z-scores for all entries during study period. The age-specific mean and standard deviation from U.S. population norms will be used to calculate Z-scores using the Centers for Disease Control Epi-Info program.
Time Frame
At baseline, week 4, week 10, week 12 and up to 2 -4 more times as standard of care visits for the duration of the study (34 weeks from randomization)
Title
Short Crohn's Disease Activity Index (sCDAI)
Description
The short Crohn's disease activity index (sCDAI) will be used to assess disease activity based on self-report via the study app. For the sCDAI, items assess general well-being, abdominal pain, and liquid stools. Respondents are asked to report on symptoms for the previous 24 hour period. Scores are calculated based on a published algorithm.
Time Frame
Weekly through study completion (34 weeks from randomization)
Title
Pediatric Ulcerative Colitis Activity Index (PUCAI)
Description
A self-reported version of the Pediatric Ulcerative Colitis Activity Index (PUCAI) will be used to assess disease activity based on self-report via the study app. For the PUCAI, respondents are asked to report on abdominal pain, bloody stools, stool consistency, stool frequency, nocturnal stools, and activity level over the prior 24-hours. A weighted, summed score is calculated with higher scores indicating worse disease (score range 0-85).
Time Frame
Weekly through study completion (34 weeks from randomization)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
7 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of Crohn's Disease (CD) or ulcerative colitis (UC) or Indeterminate colitis (IC) Age 7-18 years Enrolled in the ImproveCareNow (ICN2) registry Evidence of acute inflammation and/or elevated acute phase reactant as measured by Fecal calprotectin 1.5 times the upper limit of normal, Lactoferrin 1.5 times the upper limit of normal, CRP 1.15 times the upper limit of normal, or ESR 1.15 times the upper limit of normal (based on local reference ranges) obtained within 8 weeks of enrollment. Potential participants who are close to meeting one of the acute inflammation and/or elevated acute phase reactant markers and who meet all other study criteria will be considered for study participation on a case by case basis by the investigative study team in consultation with the patient's primary gastroenterologist. Exclusion Criteria: Complex and Unstable IBD: Currently or within the past 9 months has had an abscess, fistula, stricturing CD, or ostomy Severe disease activity as measured by a short Pediatric Crohn's Disease Activity Index (SPCDAI) score of >45 or Pediatric Ulcerative Colitis Activity Index (PUCAI) score of >60 assessed within three weeks of enrollment Ever had history of full colectomy Hospitalization or surgery planned within 3 months Ongoing active gastrointestinal infection Severe Malnutrition (BMI less than 5th percentile) Recent medication changes including: Thiopurines, natalizumab, or methotrexate started within 8 weeks prior to enrollment Anti TNF (infliximab, adalimumab) started within 8 weeks prior to enrollment Vedolizumab started within 16 weeks prior to enrollment Increase in corticosteroids within 4 weeks of screening or have dose >20 mg prednisone or equivalent Evidence of Other Complicating Medical Issues: Other serious medical conditions, such as neurological, liver, kidney, or systemic disease Serious psychological or psychiatric conditions such as eating disorders or self-harm Pregnancy Tobacco, alcohol, or illicit drug abuse Inability to Complete the Protocol Non-English speaking participants On SCD or modified SCD anytime within 8 weeks of enrollment If an otherwise eligible patient is on SCD or modified SCD within 8 weeks of enrollment but they are noncompliant per the determination of the patient's dietitian/primary gastroenterologist, then this patient is eligible to participant in the study. Participants on a vegan diet Lack of smart phone and data plan for participating caregiver Participating in another concurrent intervention study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Heather C Kaplan, MD
Organizational Affiliation
Children's Hospital Medical Center, Cincinnati
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Lisa Opipari-Arrigan, PhD
Organizational Affiliation
Children's Hospital Medical Center, Cincinnati
Official's Role
Principal Investigator
Facility Information:
Facility Name
Arkansas Children's Hospital
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72202
Country
United States
Facility Name
Children's Hospital of Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
UCSF Benioff Children's Hospital Oakland
City
Oakland
State/Province
California
ZIP/Postal Code
94609
Country
United States
Facility Name
Lucile Packard Children's Hospital
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
University of California San Francisco Benioff Children's Hospita;
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Facility Name
Nemours, Alfred I duPont Hospital for Children
City
Wilmington
State/Province
Delaware
ZIP/Postal Code
19803
Country
United States
Facility Name
Nemours Children's Speciality Care
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32207
Country
United States
Facility Name
Nemours Children's Hospital
City
Orlando
State/Province
Florida
ZIP/Postal Code
32827
Country
United States
Facility Name
GI Care for Kids
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Name
Riley Hospital for Children
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Children's Mercy Hospital
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
Levine Children's Hospital
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28203
Country
United States
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
Oregon Health Sciences University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Dell Children's Medical Center of Central Texas
City
Austin
State/Province
Texas
ZIP/Postal Code
78723
Country
United States
Facility Name
UT Soutwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235
Country
United States
Facility Name
Pediatric Specialists of Virginia
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Facility Name
Children's Hospital of the King's Daughters
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23507
Country
United States
Facility Name
Seattle Children's
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
We intend to provide access to the de-identified, HIPAA-compliant databases as required within a year after the study has been completed. Data plans, analysis plans, data dictionaries, study manuals and annotated case report forms will be made available, upon request, in a read-only format (PDF). Each dataset will be accompanied by appropriate documentation listing each variable, variable definition, decode values (if appropriate), an indication of the variable as a source collected or derived variable, and derivation algorithms for any derived values. Datasets will be available as SAS, SAS transport, XML or CSV with labels. Other formats may be created if requested. All necessary security measures will be taken to ensure patient privacy and confidentiality, and details on how data may be used, including the use of de-identified data sets, will be included in the informed consent.
IPD Sharing Time Frame
Within a year after study completion.
Citations:
PubMed Identifier
35442220
Citation
Kaplan HC, Opipari-Arrigan L, Yang J, Schmid CH, Schuler CL, Saeed SA, Braly KL, Chang F, Murphy L, Dodds CM, Nuding M, Liu H, Pilley S, Stone J, Woodward G, Yokois N, Goyal A, Lee D, Yeh AM, Lee P, Gold BD, Molle-Rios Z, Zwiener RJ, Ali S, Chavannes M, Linville T, Patel A, Ayers T, Bassett M, Boyle B, Palomo P, Verstraete S, Dorsey J, Kaplan JL, Steiner SJ, Nguyen K, Burgis J, Suskind DL; ImproveCareNow Pediatric IBD Learning Health System. Personalized Research on Diet in Ulcerative Colitis and Crohn's Disease: A Series of N-of-1 Diet Trials. Am J Gastroenterol. 2022 Jun 1;117(6):902-917. doi: 10.14309/ajg.0000000000001800. Epub 2022 Apr 20.
Results Reference
result

Learn more about this trial

Personalized Research on Diet in Ulcerative Colitis and Crohn's Disease

We'll reach out to this number within 24 hrs