GWAS to Identify Predictive Genetic Factors for the Success of Dietary Intervention in the Treatment of IBS Symptoms

Whole Genome Association Study (GWAS) to Identify Predictive Genetic Factors for the Success of Dietary Intervention in the Treatment of Irritable Bowel Syndrome (IBS) Symptoms

This is a GWAS that aims to identify possible single nucleotide polymorphisms (SNPs) that are associated with the response in a combined dietary pattern low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols and Meditteranean diet (MED-LFD) in a small group of patients with Irritable Bowel Syndrome (IBS).

Study Overview

• Status: Recruiting
• Conditions: Irritable Bowel Syndrome (IBS); Mediterranean Diet; Single Nucleotide Polymorphisms; Genome-wide Association Study; FODMAP Diet
• Intervention / Treatment: Other: Med-LFD intervention

Detailed Description

Irritable bowel syndrome (IBS) is a very common chronic gastrointestinal disorder. Several factors seem to contribute to its development, such as psychological stress, intestinal dysbiosis, infections, post-traumatic syndrome and genetic predisposition. Regarding the nutritional management of IBS, there are several approaches to alleviate symptoms, such as the low-fructose diet low in fermentable oligosaccharides, disaccharides, monosaccharides and FODMAP polyols (LFD), recommendations from the British Institute of Health and Care Excellence (NICE) and the recently proposed combination of the Mediterranean diet and LFD (MED-LFD) proposed by our Research Group. However, genetic background expressed in single nucleotide polymorphisms (SNPs) appears to influence the response to even dietary interventions.

The aim of this GWAS is to identify SNPs that are associated with the negative or positive response to the diet.

At the baseline, blood samples will be collected for DNA extraction. Genotyping will be based on Next Generation Sequencing (NGS) technology to detect genetic factors associated with the effectiveness of the intervention. Symptom severity will be measured by the IBS-SSS scale. Mental health status will be assessed with the HADS (Hospital Anxiety and Depression Scale) questionnaire.

Patients will be recruited by the Department of Clinical Nutrition, Attikon University General Hospital, where the nutritional intervention will be carried out.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Konstantinos Triantafyllou, Proffesor; Phone Number: +306977402690; Email: ktriant@med.uoa.gr
• Study Contact Backup: Name: Maroulla Nikolaki, PhD (c); Phone Number: +30 6979376752; Email: mnikolaki@med.uoa.gr

Study Locations

• Greece
  • Athens, Greece, 12462
    • Recruiting
    • Attikon General University Hospital of Athens

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients 18-65 years with IBS (fullfiling ROME IV criteria) who have IBS-SSS>175. People with any concomitant disease requiring specialized nutrition, pregnant or lactating women will be excluded.

Description

Inclusion Criteria:

• Fulfillment of the Rome IV criteria for IBS
• Provision of written informed consent.
• Commitment of availability throughout the study period.
• IBS-SSS > 175

Exclusion Criteria:

• Any concomitant disease requiring specialized nutrition (e.g. renal failure, diabetes, celiac disease, cerebrovascular disease of the central nervous system, major surgical cavity).
• Pregnancy.
• Breastfeeding.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Basic group; MED-LFD Diet for 2 - 6 weeks. After this period there will be a reintroduction phase protocol that will last 6 - 8 weeks.

Other: Med-LFD intervention; In the beginning of the intervention, blood and stool samples will be collected. All participants of the group at phase 1 (elimination phase), will initially follow the Med- LFD (2-6 weeks). At phase 2 (reintroduction phase), patients will gradually reintroduce foods rich in FODMAPs (6-8 weeks) and test their tolerance. At phase 3 (maintenance phase), following the reintroduction of foods rich in FODMAPs, patients will follow an individualized diet based on their personal tolerance (a combination of high and low FODMAPs). In the end of intervention, stool samples will be collected again.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Find single nucleotide polymorphisms (SNPs) that associate with the diet respone	Blood samples will be collected for DNA extraction. Genotyping be based on Next Generation Sequencing (NGS). Quality control (QC) filtering will be applied at individual-and variant-level using specialized software.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of symptoms severity pre and post intervention using a specialized questionnaire.	IBS- SSS contains 5 specific questions with instructions on how to score them. Each of the five questions (pain severity, pain frequency, abdominal distension severity, bowel movement satisfaction, quality of life) ranges from 0 to a maximum score of 100 using a visual analog scale (VAS) with total scores ranging from 0 to 500, with higher scores indicating more severe symptoms. Subjects can be categorized as having mild (75-175), moderate (175-300), or severe (>300) IBS. A decrease of 50 points is associated with a clinically meaningful improvement.	Baseline and through study completion (an average of 1 year)
Evaluation of the effect of interventions on gut microbiota composition between groups.	Fecal samples will be collected from each participant and stored at -80°C.	Baseline and through study completion (an average of 1 year)
Assessment of general quality of life pre and post intervention between groups	12-Item Short Form Survey (SF-12) is a 12-item questionnaire used to assess generic health outcomes from the patient's perspective, covering the eight domains of health outcomes: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional & mental health. The items are weighted and summed to provide physical and mental health scores (PCS and MCS). The two composite scores are computed using the scores on the questions that range from 0 to 100, with higher score indicating better health.	Baseline and through study completion (an average of 1 year)
Assessment of symptoms burden in general pre and post intervention.	The GSRS questionnaire was originally developed for dyspeptic patients but was later validated in patients with IBS. The GSRS is a 15-item questionnaire designed to assess common gastrointestinal symptoms. The questionnaire has five subscales, reflux, diarrhea, constipation, indigestion, and abdominal pain, with subscale scores ranging from 1 (no discomfort) to 7 (severe discomfort). Higher scores represent higher symptom burden.	Baseline and through study completion (an average of 1 year)
Assessment of anxiety and depression disorders pre and post intervention.	The Hospital Anxiety and Depression Scale (HADS) questionnaire is used for the assessment of anxiety and depression symptoms. It's a 14-item scale with seven items for each subscale, anxiety (HADS-A) and depression (HADS-D). Each item is scored on a response scale with four alternatives, ranging between 0 and 3. The total score is the sum of the 14 items, and for each subscale the score is the sum of the respective seven items (ranging from 0-21). A final score of 0-7 on each scale indicates that the patient has no symptoms, a score of 8-10 indicates mild symptoms while a score ≥11 indicates severe symptoms of anxiety and depressive disorders.	Baseline and through study completion (an average of 1 year)

Collaborators and Investigators

• Sponsor: Attikon Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2024
• Primary Completion (Estimated): September 15, 2026
• Study Completion (Estimated): February 15, 2027

Study Registration Dates

• First Submitted: January 14, 2025
• First Submitted That Met QC Criteria: March 29, 2025
• First Posted (Actual): April 6, 2025

Study Record Updates

• Last Update Posted (Actual): April 6, 2025
• Last Update Submitted That Met QC Criteria: March 29, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: nutrigenetics; diet response
• Additional Relevant MeSH Terms: Pathologic Processes; Intestinal Diseases; Disease; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Colonic Diseases, Functional; Irritable Bowel Syndrome; Syndrome
• Other Study ID Numbers: ΕΒΔ407/30.5.2024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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