Predictive Value of Hydrogen/Methane Lactose Breath Testing on the Therapeutic Effect of Lactose-free Diet in Moderate to Severe ROME IV IBS.

Lactose intolerance (LI) results from lactose malabsorption (LM) secondary to insufficient hydrolysis of the disaccharide lactose into galactose and glucose (Misselwitz 2019). The undigested lactose will eventually reach the colon, resulting in fermentation from colonic bacteria with production of different compounds such as short chain fatty acids, carbon dioxide, H2 and methane (Catanzaro 2021). These compounds have an osmotic effect and can stimulate colonic contractions. These pathophysiological mechanisms encountered in patients suffering from LI generate symptoms, such as abdominal pain and cramps, flatulence, diarrhea, borborygmi among others. As dairy products are highly present in our Western diet, LI will often be considered in patients presenting with these symptoms and they will be referred for further testing. When LM is diagnosed, a lactose-free diet (LFD) will be advocated to alleviate symptoms. However, studies indicate that individuals with LM should tolerate up to 12 g of lactose when administered in a single dose (Suchy 2010).

Irritable bowel syndrome (IBS) is another frequently encountered disorder. According to the Rome IV criteria, it is characterized by abdominal pain associated with a change in stool frequency or consistency, or with symptomatic improvement by defecation (Mearin 2016). Associated symptoms, such as bloating and flatulence, are frequently reported. As such, discerning between IBS and LI based on symptoms alone can be challenging. Moreover lactose is considered part of the so-called fermentable oligo-, di-, monosaccharides and polyols (FODMAPs). A low FODMAP diet has been advocated for IBS with beneficial response in at least part of the patients (Halmos 2014).

Many studies investigated the role of lactose in IBS. These studies were performed in the pre-Rome IV era and before standardized interpretation rules for Hydrogen breath testing (H2BT) were published (meta-analysis by Varju 2019). This meta-analysis indicated that subjective LI was more frequently reported by IBS patients, but also objectively more prevalent in IBS patients, when assessed by any test modality. However, the role of a LFD in IBS remains uncertain.

This study aims to:

• Determine if the diagnosis of LM by H2BT predicts the short-term and long-term response to a LFD in moderate to severe IBS as defined by Rome IV criteria;
• Determine the changes in quality of life in response to a LFD in ROME IV IBS patients.

Study Overview

• Status: Recruiting
• Conditions: Irritable Bowel Syndrome; Lactose Intolerant
• Intervention / Treatment: Other: low fat diet

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Sébastien Kindt, MD; Phone Number: 37 15 +32 2 476; Email: Sebastien.kindt@uzbrussel.be

Study Locations

• Belgium
  • Brussels
    • Jette, Brussels, Belgium, 1090
      • Recruiting
      • UZ Brussel
      • Contact: Sébastien Kindt, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Fulfilling the ROME IV criteria for IBS;
• Moderate symptom severity as defined by a IBS-SSS > 175;
• Consumption of lactose containing products.

Exclusion Criteria:

• Clinical suspicion of an organic disorder different from LI or IBS (patients can be included when this disorder had been excluded);
• Known lactose intolerance or malabsorption;
• Known inflammatory bowel disorder;
• Known intestinal motility disorder;
• Alcohol (defined as more than 14 U per week) or other substance abuse;
• Active psychiatric disorder;
• Known systemic or auto-immune disorder with implication for the GI system;
• Prior abdominal surgery (with the exception of appendectomy);
• Any prior diagnosis of cancer other than basocellular carcinoma;
• Current chemotherapy;
• History of gastro-enteritis in the past 8 weeks;
• Intake of antibiotics, pre- or probiotics during the past 8 weeks;
• Dietary supplements unless taken at a stable dose for more than 8 weeks;
• Treatment with neuromodulators (one neuromodulator taken at a stable dose for more than 12 weeks is allowed);
• Treatment with spasmolytic agents, opioids, loperamide, gelatin tannate or mucoprotect-ants during the past 8 weeks;
• LFD or low FODMAP diet in the past

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: H2BT-positive	Other: low fat diet; A trained dietitian will provide instruction of the LFD according to standard practice.
Experimental: H2BT-negative	Other: low fat diet; A trained dietitian will provide instruction of the LFD according to standard practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
symptomatic improvement	To compare the symptomatic improvement by a LFD in Rome IV IBS patients with and without LM according to a H2BT.	from baseline till visit 4 (week 4)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
reduction in Irritable bowel syndrome - symptom severity scale	reduction in IBS-SSS at the end of 4 weeks of a LFD in Rome IV IBS subjects identified as lactose mal-absorbers vs. lactose absorbers by lactose H2BT	baseline till visit 4 (week 4)

Collaborators and Investigators

• Sponsor: Universitair Ziekenhuis Brussel

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2021
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: July 13, 2021
• First Submitted That Met QC Criteria: July 13, 2021
• First Posted (Actual): July 23, 2021

Study Record Updates

• Last Update Posted (Estimated): December 1, 2023
• Last Update Submitted That Met QC Criteria: November 30, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Irritable Bowel Syndrome
• Other Study ID Numbers: PreVaIL

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