Prevention of Inflammatory Bowel Diseases in Persons at Risk The PIONIR (Preventing IBD Onset in Individuals at Risk) Trial (PIONIR)

Preventing IBD Onset in Individuals at Risk

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 First Degree Relatives of patients with Crohn's disease, including 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.

Study Overview

• Status: Completed
• Conditions: Inflammatory Bowel Diseases
• Intervention / Treatment: Other: Tasty&Healthy; Other: Habitual diet

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.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Israel
  • Jerusalem, Israel
    • Shaare Zedek Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 35 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion criteria

• Clinically healthy subjects (i.e. lack of symptoms that may suggest IBD) who are First degree relatives of someone with CD with a high faecal calprotectin (FC)>70μg/g or subjects who have a risk factor for example elevated GRS. Where available LMR will also be assessed to identify subjects ranked as top 100 at risk of CD.
• Younger than 39 years of age, in order to maximize future risk of developing CD.
• No overt ulcerations (other than aphthous ulcerations) in the ileum or colon. Some degree of inflammation may be seen in these high-risk subjects with increased risk parameters and this does not necessarily prompt the diagnosis of CD. Moreover, in this proof of concept study we would like to have those with the highest risk (hence some degree of initial inflammation) but without macroscopic inflammation that clearly is associated with the diagnosis of CD. Patency capsule and VCE procedure will be performed if the subjects calprotectin levels are >70μg/g.

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Tasty&Healthy; Tasty&Healthy intervention: subjects will receive dietary advice to exclude pro-inflammatory dietary components	Other: Tasty&Healthy; exclude pro-inflammatory dietary components
Other: Habitual diet; Habitual diet: subjects will continue their habitual diet.	Other: Habitual diet; subjects will continue their habitual diet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction in fecal calprotectin (FC) levels over the 8 week Tasty & Healthy dietary intervention, reflecting improvement in intestinal inflammatory activity.	Fecal calprotectin (FC) is a validated, sensitive marker of intestinal inflammation and reflects short term biological changes expected from the Tasty & Healthy intervention. For this reason, the primary endpoint is a reduction in FC over the 8 weeks of the intervention.	8 weeks of Tasty&Healthy diet.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ability to maintain a balanced diet as measured by food diaries.	Will be assessed by daily caloric intake and nutritional components.	8 weeks of Tasty&Healthy diet.
Adherence with the interventions, including assessment of faecal gluten.	Will be assessed using ELISA kit- Buhlman fCAL Elisa	8 weeks of Tasty&Healthy diet.
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.	8 weeks of Tasty&Healthy diet.
Change in routine blood biomarkers over the course of the 8 week intervention	Biomarkers will be measured at baseline, and end of each intervention in hospital laboratories.	8 weeks of Tasty&Healthy intervention
Change in the GEM integrative risk score	The GEM integrative risk score assesses how a participant's composite GEM risk score changes from baseline to after the intervention. The iGRS integrates multiple biological markers to reflect overall risk for developing Crohn's disease. A reduction in the score would indicate a favorable shift in these modifiable risk factors.	8 weeks of Tasty & Healthy intervention
Change in Microbiome risk score (MRS)	Decreased level of Microbiome risk score. The Microbiome risk score is a test we develop to classify individuals according to their risk to develop Crohn's disease onset.	8 weeks of Tasty&Healthy diet.
Change in Lactulose-Mannitol Ratio (LMR).	Decreased level of urinary fractional excretion ratio of Lactulose to Mannitol (LMR). The LMR is an in vivo test that allow quantification of intestinal barrier permeability that is associated with risk to develop Crohn's disease.	8 weeks of Tasty&Healthy diet.
Change in Serum Metabolomics pre and post-intervention	Change in levels of stool, urine, and serum metabolites. 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.	8 weeks of Tasty&Healthy diet.
Change in Serum Proteomics pre and post-intervention	Change in serum proteomics. 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.	8 weeks of Tasty&Healthy diet.

Collaborators and Investigators

• Sponsor: Shaare Zedek Medical Center
• Collaborators: University of Manitoba; The Hospital for Sick Children; University of British Columbia; McGill University; University of Calgary; Samuel Lunenfeld Research Institute, Mount Sinai Hospital; IWK Health Centre; The Governors of the University of Alberta; Beilinson Hospital, Petach Tikva,Israel
• Investigators: Principal Investigator: Dan Turner, Prof, Saare Zedek Medical Center

Publications and helpful links

General Publications

• 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.
• Department of Error. Lancet. 2020 Oct 3;396(10256):e56. doi: 10.1016/S0140-6736(20)32028-6. No abstract available.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 4, 2021
• Primary Completion (Actual): January 15, 2026
• Study Completion (Actual): January 15, 2026

Study Registration Dates

• First Submitted: October 4, 2021
• First Submitted That Met QC Criteria: January 26, 2022
• First Posted (Actual): January 27, 2022

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 22, 2026
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Chron
• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases
• Other Study ID Numbers: PIONIR trial

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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