Digestive Enzyme Formulation Intervention in IBS Patients Who Previously Clinically Responded to Mediterranean LFD

Digestive Enzyme Formulation Intervention in Irritable Bowel Syndrome Patients Who Previously Clinically Responded to Mediterranean Low FODMAP Diet: A Single-Arm Clinical Trial

Irritable bowel syndrome (IBS) is a highly prevalent chronic functional gastrointestinal disorder. The cardinal symptoms include abdominal pain, flatulence, bloating, and changes in bowel habits related to stool frequency and consistency, in the absence of detectable structural and biochemical abnormalities1,2. The prevalence is estimated at 5-10% among different ethnicities3. A low FODMAP diet is the most common dietary intervention with clinically proven benefits in symptom management and quality of life improvement of patients with Irritable Bowel Syndrome (IBS)4. Recently, a dietary digestive enzyme formulation (FODZYME©) claims similar efficacy in symptom management based on an ex-vivo study5. The study aims to examine the clinical efficacy of this formulation in managing IBS symptoms in patients who have previously clinically responded to a low FODMAP diet.

Study Overview

• Status: Recruiting
• Conditions: Irritable Bowel Syndrome
• Intervention / Treatment: Dietary supplement: digestive enzymes

Detailed Description

IBS patients who participated in a two-arm clinical trial (ClinicalTrials.gov ID: NCT03997708) and responded to the Mediterranean Diet Adjusted Low FODMAP (MED-LFD) Diet will be considered eligible if their symptoms recurred one year after their initial response to the dietary intervention. Among them, patients without any or mild symptoms, defined as IBS severity scoring system (IBS-SSS) ≤ 175, will be excluded. Moreover, subjects who were randomized to the MED-LFD arm in the previous study, but could not adhere to the dietary intervention, will be included too.

A jar containing the digestive enzymes in the form of powder will be provided to each patient at the start of the study. Patients will be instructed to use the powder formulation according to manufacturer instructions for 1 month. To assess compliance, the weight of each jar will be measured both at the initiation and the end of the study. Patients will also be asked on three different days (one day from the weekend), to estimate the average number of meals per day. Due to the limited sample size (54 patients who received the MED-LFD diet in the previous phase will be screened for eligibility), a control group will be omitted. To reduce the placebo effect, patients will be misinformed that half will take a placebo formulation, randomly.

All patients will be thoroughly trained regarding the proper consumption of the powder (exact dose, timing, etc.), through personal training, videos, leaflets, and other type of training materials.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: AREZINA KASTI, PhDc; Phone Number: +30 6942917860; Email: kastiare@yahoo.gr
• Study Contact Backup: Name: Konstantinos Triantafyllou, Professor; Phone Number: +30 6977402690; Email: ktriant@med.uoa.gr

Study Locations

• Greece
  • Athens, Greece, 12462
    • Recruiting
    • Attikon University General Hospital
    • Contact: Arezina Kasti; Phone Number: +30 2105832565; Email: kastiare@yahoo.gr
  • Athens
    • Chaïdári, Athens, Greece
      • Recruiting
      • Attikon University General Hospital
      • Contact: MAROULLA I NIKOLAKI, phD (c); Phone Number: 6979376752; Email: mnikolaki@med.uoa.gr
      • Contact: arezina kasti; Phone Number: 6942917860; Email: kastiare@yahoo.gr

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Provision of written informed consent.
• Commitment to availability throughout the study period.
• Patients who fulfilled the Rome IV criteria for IBS (IBS-D, IBS-M, IBS-U) participated in the two-arm clinical trial (ClinicalTrials.gov ID: NCT03997708) as responders to the Mediterranean Diet Adjusted to Low FODMAP (MED-LFD) (if their symptoms recurred -with IBS-SSS > 175- one year after their initial response to the dietary intervention).
• Subjects randomized to the MED-LFD arm of the previous study who could not adhere to the dietary intervention.

Exclusion Criteria:

• Patients who did not take part in the aforementioned study
• Patients who were randomized in the NICE group
• Patients with IBS-SSS<175.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: digestive enzymes group; Patients will be instructed to use a powder formulation according to manufacturer instructions and according to the meals that they consume per day, for 1 month. To reduce the placebo effect, patients will be misinformed that half will take a placebo formulation, randomly.

Dietary supplement: digestive enzymes; A jar or single-dose sachets containing the digestive enzymes in the form of powder will be provided to each patient at the study entry. Patients will be instructed to use the powder formulation according to manufacturer instructions and according to the meals that they consume per day, for 1 month. Participants will be asked to return the jar or the single dose sachets with the remaining product to assess compliance either by weighting the jar or by counting the number of single-dose sachets returned. To reduce the placebo effect, patients will be misinformed that half will take a placebo formulation, randomly. Participants will be asked to return the jar or the single-dose sachets with the remaining product to assess compliance either by weighting the jar or by counting the number of single-dose sachets returned.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in IBS-SSS from baseline to follow-up	Changes in IBS-SSS from baseline to follow-up in the group of patients that have responded to MED-LFD in the past. The IBS-SSS questionnaire consists of 5 specific questions6. Each of the five questions (pain severity, pain frequency, abdominal distension severity, bowel movement satisfaction, quality of life) ranges from a minimum score of 0 to a maximum score of 100, using a visual analog scale (VAS), with total scores ranging from 0 to 500.	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the Gastrointestinal Symptom Rating Scale - IBS version (GSRS-IBS).	The GSRS questionnaire is validated in patients with IBS. GSRS-IBS consists of 13 items, designed to assess gastrointestinal symptoms specifically for IBS patients. Each item is rated based on a 7-point Likert scale (1. "No discomfort at all"; 2. "Minor discomfort"; 3. "Mild discomfort"; 4. "Moderate discomfort"; 5. "Moderately severe discomfort"; 6. "Severe discomfort"; 7. "Very severe discomfort"). The questionnaire has a total score and five subscales (pain, bloating, constipation, diarrhea, and satiety), calculated by summing all questions corresponding to each scale and dividing with the number of questions summed in each scale. Both total and subscale scores are ranging from 1 (no discomfort) to 7 (severe discomfort), with higher scores representing increased symptom burden.	1 month
Changes in SF-12.	SF-12 is a 12-item questionnaire used to assess generic health outcomes from the patient's perspective, covering two domains of health outcomes: physical functioning and mental health. The items are weighted and summed to provide physical and mental health scores. The two composite scores are computed using the scores on the questions that range from 0 to 100, with higher score indicating better QoL. SF-12 is validated also in the Greek population.	1 month
Changes in IBS-Qol.	The IBS-QoL assesses the degree to which IBS interfered with quality of life over the past 30 days10. It is a self-reported quality of life measure, which includes eight domains, such as dysphoria, interference with activity, body image, health worry, food avoidance, social relations, sexual and relationship issues. Each of them is rated based on a 5-point Likert scale (1. "Not at all"; 2." Slightly"; 3. "Moderately"; 4. "Quite a bit" 5. "Extremely/ A great deal").	1 month

Collaborators and Investigators

• Sponsor: Attikon Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2024
• Primary Completion (Estimated): October 10, 2025
• Study Completion (Estimated): March 30, 2026

Study Registration Dates

• First Submitted: December 10, 2024
• First Submitted That Met QC Criteria: December 23, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 6, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: digestive enzymes; low FODMAP Diet; MED-LFD
• 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: ΕΒΔ 185/04-03-2024

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No