Prevention of Inflammatory Bowel Diseases in Persons at Risk The PIONIR (Preventing IBD Onset in Individuals at Risk) Trial (PIONIR)
Primary Purpose
Inflammatory Bowel Diseases
Status
Recruiting
Phase
Not Applicable
Locations
Israel
Study Type
Interventional
Intervention
Tasty&Healthy
Habitual diet
Sponsored by
About this trial
This is an interventional prevention trial for Inflammatory Bowel Diseases focused on measuring Chron
Eligibility Criteria
Inclusion criteria
- Clinically healthy subjects (i.e. lack of symptoms that may suggest IBD) that are enrolled to the GEM project, with a high faecal calprotectin (FC)>70μg/g or chrons multiplex or elevated GRS score or increased microbiome risk score.
- Younger than 36 years of age, in order to maximize future risk of developing CD.
- No overt ulcerations (other than aphthous ulcerations) in the colon.
Exclusion Criteria:
- Ulcerative colitis (UC) or IBD-unclassified (IBDU) diagnosis
- The use of antibiotics in the preceding month
- Prior intestinal resection
- Pregnancy (and up until six months after giving birth)
- Celiac disease or Diabetes
- Weight loss or weight gain by more than 20% body weight in the last 3 months
- Extraintestinal manifestations (Arthritis/arthralgia, iritis/uveitis, skin/mouth lesions, peri-anal disease, Other fistula).
- Underweight (children <3th BMI percentile, adult above the age of 18 years: BMI<18.5 kg/m2).
Sites / Locations
- Shaare Zedek Medical CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Other
Other
Arm Label
Tasty&Healthy
Habitual diet
Arm Description
Tasty&Healthy intervention: subjects will receive dietary advice to exclude pro-inflammatory dietary components
Habitual diet: subjects will continue their habitual diet.
Outcomes
Primary Outcome Measures
The likelihood to develop CD measured by the GRS scale.
Several important factors associated with CD onset have already been identified in the GEM analyses, such as elevated fecal calprotectin (FC), altered gut permeability, proteomics, anti-microbial serology, and microbiome composition. These parameters are potentially modifiable and will be combined into a model to construct the GEM Risk Score (GRS). The range of the GRS is 60.54682691 or higher. The higher the GRS score there is an increased chance of developing Chron's dis.
Secondary Outcome Measures
FC decreased by >30% at the end of the "Tasty&Healthy" intervention, compared to the FC before the intervention.
Decreased level of fecal calprotectin with at least 30% decline from baseline. fecal calprotectin is a test used to detect inflammation in the gastrointestinal tract and is associated with Crohn's disease onset.
Microbiome risk score (MRS) Change in one standard deviation.
Decreased level of Microbiome risk score with at least one standard deviation decline from baseline. The Microbiome risk score is a test we develop to classify individuals according to their risk to develop Crohn's disease onset.
Lactulose-Mannitol Ratio (LMR) Change in one standard deviation.
Decreased level of urinary fractional excretion ratio of Lactulose to Mannitol (LMR) with at least one standard deviation decline from baseline. The LMR is an in vivo test that allow quantification of intestinal barrier permeability that is associated with risk to develop Crohn's disease.
Change in Serum Metabolomics pre and post-intervention
Change in levels of stool, urine, and serum metabolites with at least one standard deviation difference from baseline. Metabolomics allow assessment of host chemical processes involving metabolites, small molecule substrates, intermediates and products of cell or microbial metabolism. Unit of measure is raw area count rescaled to set the median equal to 1.
Change in Serum Proteomics pre and post-intervention
Change in serum proteomics with at least one standard deviation different from baseline. Proteomics allows to assess initiators of most biological processes such as enzymes, cytokines, and transcription factors that contribute to Crohn's disease onset. Unit of measure is normalized protein expression.
Change in Serology pre and post-intervention
Change in antimicrobial antibodies response with at least one standard deviation different from baseline. Serum antimicrobial antibodies allows to assess the immune response against commensal bacteria that are associated with risk of Crohn's disease onset. Unit of measure is titer.
Ability to maintain a balanced diet as measured by food diaries.
Will be assessed by daily caloric intake and nutritional components.
Adherence with the interventions, including assessment of faecal gluten.
Will be assessed using ELISA kit- Buhlman fCAL Elisa
Satisfaction with the treatment received, as assessed by the Satisfaction with Food-Related Life (SFRL) questionnaire.
Will be assessed by the SFRL questionnaire - Grunert KG, Dean M, Raats MM, Nielsen NA, Lumbers M; Food in Later Life Team. A measure of satisfaction with food-related life. Appetite. 2007 Sep;49(2):486-93. doi: 10.1016/j.appet.2007.03.010. Epub 2007 Mar 24. PMID: 17481776.
Full Information
NCT ID
NCT05211518
First Posted
October 4, 2021
Last Updated
December 28, 2022
Sponsor
Shaare Zedek Medical Center
Collaborators
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, The Hospital for Sick Children
1. Study Identification
Unique Protocol Identification Number
NCT05211518
Brief Title
Prevention of Inflammatory Bowel Diseases in Persons at Risk The PIONIR (Preventing IBD Onset in Individuals at Risk) Trial
Acronym
PIONIR
Official Title
Preventing IBD Onset in Individuals at Risk
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
May 4, 2021 (Actual)
Primary Completion Date
May 1, 2023 (Anticipated)
Study Completion Date
May 1, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shaare Zedek Medical Center
Collaborators
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, The Hospital for Sick Children
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
The goal of this study is to explore in a cross over randomized controlled trial, the ability of the Tasty&Healthy dietary intervention (NCT04239248) to alter the parameters associated with future risk of developing Chron's disease (CD) using subjects identified in the Genetic Environmental Microbiome (GEM) Study as having a high-risk score. Specifically, the investigators aim to determine if the Tasty&Healthy dietary intervention can decrease the overall GEM Risk Score (GRS) and/or to alter the individual biological parameters that contribute to this score. The investigators hypothesize that the Tasty&Healthy dietary approach will alter the risk of CD as reflected by a decrease in the GRS.
Detailed Description
Several important factors associated with CD onset have already been identified in the GEM analyses, such as elevated faecal calprotectin(FC),altered gut permeability, proteomics, anti-microbial serology, and microbiome composition. These parameters are combined into the GEM Risk Score (GRS).
The first-line therapy in children with CD, according to ECCO/ESPGHAN guidelines, is exclusive enteral nutrition (EEN), meaning 8-12 weeks of exclusive liquid formula. Nutritional therapy may alter intestinal inflammation by several mechanisms, including modulation of the microbiome and an effect on intestinal permeability, both factors assessed in the GEM cohort. EEN is safe and effective, but it is challenging to implement.
Several diets, based on solid foods, have been proposed as alternatives to EEN in an attempt to increase feasibility, three of which have the most data.
Specific carbohydrate diet (SCD) restricts carbohydrates and processed foods and has been long used with variable reported effectiveness.
The CD-TREAT diet induced a positive change to the microbiome, children with active CD entered clinical remission with decreased inflammatory markers.
Crohn's Disease Exclusion Diet (CDED) is based on the exclusion of processed and pro-inflammatory foods, similar to Tasty&Healthy. A recent RCT of CDED diet with 50% liquid formula showed comparable effectiveness as EEN, including normalization of FC and positive effect on the microbiome.
However, the allowed dietary components are not liberal, and the diet is rigid, making it unsuitable as a prevention measure.
In 2014, a cook-book named "Tasty&Healthy" was published as a simple approach to dietary treatment based on the best available evidence. A steering committee of physicians experienced in IBD and nutrition, as well as leading IBD dieticians, reviewed results of dietary studies from animal models, humans and epidemiological cohorts. This review resulted in agreed-upon foods that may aggravate inflammation and thus should be excluded, including all processed and industrialized food, animal fat (dairy, meat), gluten and sugar. Overall, allowed foods in liberal quantities are those prepared at home from readily available ingredients such as fruits, vegetables, fish and shellfish, poultry, oats, eggs, non-gluten grains and legumes. Tasty&Healthy is not a specific diet; it is a dietary approach in which the allowed foods are not structured or restricted. This approach allows flexibility to increase adherence In this study, The Investigators hypothesize that the Tasty&Healthy dietary approach will alter the risk of CD as reflected by a decrease in the GEM CD risk score or alteration of its individual components.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Inflammatory Bowel Diseases
Keywords
Chron
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Tasty&Healthy
Arm Type
Other
Arm Description
Tasty&Healthy intervention: subjects will receive dietary advice to exclude pro-inflammatory dietary components
Arm Title
Habitual diet
Arm Type
Other
Arm Description
Habitual diet: subjects will continue their habitual diet.
Intervention Type
Other
Intervention Name(s)
Tasty&Healthy
Intervention Description
exclude pro-inflammatory dietary components
Intervention Type
Other
Intervention Name(s)
Habitual diet
Intervention Description
subjects will continue their habitual diet.
Primary Outcome Measure Information:
Title
The likelihood to develop CD measured by the GRS scale.
Description
Several important factors associated with CD onset have already been identified in the GEM analyses, such as elevated fecal calprotectin (FC), altered gut permeability, proteomics, anti-microbial serology, and microbiome composition. These parameters are potentially modifiable and will be combined into a model to construct the GEM Risk Score (GRS). The range of the GRS is 60.54682691 or higher. The higher the GRS score there is an increased chance of developing Chron's dis.
Time Frame
8 weeks of Tasty&Healthy diet.
Secondary Outcome Measure Information:
Title
FC decreased by >30% at the end of the "Tasty&Healthy" intervention, compared to the FC before the intervention.
Description
Decreased level of fecal calprotectin with at least 30% decline from baseline. fecal calprotectin is a test used to detect inflammation in the gastrointestinal tract and is associated with Crohn's disease onset.
Time Frame
8 weeks of Tasty&Healthy diet.
Title
Microbiome risk score (MRS) Change in one standard deviation.
Description
Decreased level of Microbiome risk score with at least one standard deviation decline from baseline. The Microbiome risk score is a test we develop to classify individuals according to their risk to develop Crohn's disease onset.
Time Frame
8 weeks of Tasty&Healthy diet.
Title
Lactulose-Mannitol Ratio (LMR) Change in one standard deviation.
Description
Decreased level of urinary fractional excretion ratio of Lactulose to Mannitol (LMR) with at least one standard deviation decline from baseline. The LMR is an in vivo test that allow quantification of intestinal barrier permeability that is associated with risk to develop Crohn's disease.
Time Frame
8 weeks of Tasty&Healthy diet.
Title
Change in Serum Metabolomics pre and post-intervention
Description
Change in levels of stool, urine, and serum metabolites with at least one standard deviation difference from baseline. Metabolomics allow assessment of host chemical processes involving metabolites, small molecule substrates, intermediates and products of cell or microbial metabolism. Unit of measure is raw area count rescaled to set the median equal to 1.
Time Frame
8 weeks of Tasty&Healthy diet.
Title
Change in Serum Proteomics pre and post-intervention
Description
Change in serum proteomics with at least one standard deviation different from baseline. Proteomics allows to assess initiators of most biological processes such as enzymes, cytokines, and transcription factors that contribute to Crohn's disease onset. Unit of measure is normalized protein expression.
Time Frame
8 weeks of Tasty&Healthy diet.
Title
Change in Serology pre and post-intervention
Description
Change in antimicrobial antibodies response with at least one standard deviation different from baseline. Serum antimicrobial antibodies allows to assess the immune response against commensal bacteria that are associated with risk of Crohn's disease onset. Unit of measure is titer.
Time Frame
8 weeks of Tasty&Healthy diet.
Title
Ability to maintain a balanced diet as measured by food diaries.
Description
Will be assessed by daily caloric intake and nutritional components.
Time Frame
8 weeks of Tasty&Healthy diet.
Title
Adherence with the interventions, including assessment of faecal gluten.
Description
Will be assessed using ELISA kit- Buhlman fCAL Elisa
Time Frame
8 weeks of Tasty&Healthy diet.
Title
Satisfaction with the treatment received, as assessed by the Satisfaction with Food-Related Life (SFRL) questionnaire.
Description
Will be assessed by the SFRL questionnaire - Grunert KG, Dean M, Raats MM, Nielsen NA, Lumbers M; Food in Later Life Team. A measure of satisfaction with food-related life. Appetite. 2007 Sep;49(2):486-93. doi: 10.1016/j.appet.2007.03.010. Epub 2007 Mar 24. PMID: 17481776.
Time Frame
8 weeks of Tasty&Healthy diet.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion criteria
Clinically healthy subjects (i.e. lack of symptoms that may suggest IBD) that are enrolled to the GEM project, with a high faecal calprotectin (FC)>70μg/g or chrons multiplex or elevated GRS score or increased microbiome risk score.
Younger than 36 years of age, in order to maximize future risk of developing CD.
No overt ulcerations (other than aphthous ulcerations) in the colon.
Exclusion Criteria:
Ulcerative colitis (UC) or IBD-unclassified (IBDU) diagnosis
The use of antibiotics in the preceding month
Prior intestinal resection
Pregnancy (and up until six months after giving birth)
Celiac disease or Diabetes
Weight loss or weight gain by more than 20% body weight in the last 3 months
Extraintestinal manifestations (Arthritis/arthralgia, iritis/uveitis, skin/mouth lesions, peri-anal disease, Other fistula).
Underweight (children <3th BMI percentile, adult above the age of 18 years: BMI<18.5 kg/m2).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Gili Focht, Study Director
Phone
972-25645028
Email
gilif@szmc.org.il
First Name & Middle Initial & Last Name or Official Title & Degree
Elisheva Shachmon, R.N
Phone
972524749263
Email
elishevas@szmc.org.il
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dan Turner, Prof
Organizational Affiliation
Saare Zedek Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Shaare Zedek Medical Center
City
Jerusalem
Country
Israel
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gili Focht
Phone
+972 25645028
Email
gilif@szmc.org.il
First Name & Middle Initial & Last Name & Degree
Dan Turner, MD
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
33438721
Citation
Stulman MY, Asayag N, Focht G, Brufman I, Cahan A, Ledderman N, Matz E, Chowers Y, Eliakim R, Ben-Horin S, Odes S, Dotan I, Balicer RD, Benchimol EI, Turner D. Epidemiology of Inflammatory Bowel Diseases in Israel: A Nationwide Epi-Israeli IBD Research Nucleus Study. Inflamm Bowel Dis. 2021 Oct 20;27(11):1784-1794. doi: 10.1093/ibd/izaa341.
Results Reference
background
PubMed Identifier
33010847
Citation
Department of Error. Lancet. 2020 Oct 3;396(10256):e56. doi: 10.1016/S0140-6736(20)32028-6. No abstract available.
Results Reference
background
PubMed Identifier
32002671
Citation
Beard JA, Franco DL, Click BH. The Burden of Cost in Inflammatory Bowel Disease: A Medical Economic Perspective and the Future of Value-Based Care. Curr Gastroenterol Rep. 2020 Jan 30;22(2):6. doi: 10.1007/s11894-020-0744-z.
Results Reference
background
PubMed Identifier
31937567
Citation
Barnes C, Ashton JJ, Borca F, Cullen M, Walker DM, Beattie RM. Children and young people with inflammatory bowel disease attend less school than their healthy peers. Arch Dis Child. 2020 Jul;105(7):671-676. doi: 10.1136/archdischild-2019-317765. Epub 2020 Jan 14.
Results Reference
background
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Prevention of Inflammatory Bowel Diseases in Persons at Risk The PIONIR (Preventing IBD Onset in Individuals at Risk) Trial
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