Clinical trial NCT05211518: Prevention of Inflammatory Bowel Diseases in Persons At Risk the PIONIR (Preventing IBD Onset in Individuals At Risk) Trial
Official title: Preventing IBD Onset in Individuals At Risk
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Inflammatory Bowel Diseases
Keywords: Chron
Lead sponsor: Shaare Zedek Medical Center
Sponsor class: OTHER
Collaborators: name: Samuel Lunenfeld Research Institute, Mount Sinai Hospital
name: The Hospital for Sick Children
name: The Governors of the University of Alberta
name: University of Manitoba
name: IWK Health Centre
name: University of British Columbia
name: University of Calgary
name: McGill University
name: Beilinson Hospital, Petach Tikva,Israel
First posted: 2022-01-27
Enrollment: 30
Sex: ALL
Minimum age (years): 6
Maximum age (years): 38
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

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 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.

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.

Eligibility criteria: 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)\&gt;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 \&gt;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 \&lt;3th BMI percentile, adult above the age of 18 years: BMI\&lt;18.5 kg/m2).

Primary outcomes:
measure: The likelihood to develop CD measured by the GRS scale.
timeFrame: 8 weeks of Tasty&Healthy diet.
Secondary outcomes:
measure: FC decreased by >30% at the end of the "Tasty&Healthy" intervention, compared to the FC before the intervention.
timeFrame: 8 weeks of Tasty&Healthy diet.
measure: Microbiome risk score (MRS) Change in one standard deviation.
timeFrame: 8 weeks of Tasty&Healthy diet.
measure: Lactulose-Mannitol Ratio (LMR) Change in one standard deviation.
timeFrame: 8 weeks of Tasty&Healthy diet.
measure: Change in Serum Metabolomics pre and post-intervention
timeFrame: 8 weeks of Tasty&Healthy diet.
measure: Change in Serum Proteomics pre and post-intervention
timeFrame: 8 weeks of Tasty&Healthy diet.
measure: Change in Serology pre and post-intervention
timeFrame: 8 weeks of Tasty&Healthy diet.
measure: Ability to maintain a balanced diet as measured by food diaries.
timeFrame: 8 weeks of Tasty&Healthy diet.
measure: Adherence with the interventions, including assessment of faecal gluten.
timeFrame: 8 weeks of Tasty&Healthy diet.
measure: Satisfaction with the treatment received, as assessed by the Satisfaction with Food-Related Life (SFRL) questionnaire.
timeFrame: 8 weeks of Tasty&Healthy diet.
Other outcomes:
Locations:
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
Study officials:
affiliation: Saare Zedek Medical Center
name: Dan Turner, Prof
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: Department of Error. Lancet. 2020 Oct 3;396(10256):e56. doi: 10.1016/S0140-6736(20)32028-6. No abstract available.
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.
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.