An Intervention Study Using HMOs to Improve IBS Symptoms

NCT06281600 | Recruiting DMC

• 2 other identifiers: REC: 23/SW/0042326109
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

There is now strong evidence implicating the human gut microbiota in many gastrointestinal diseases, including irritable bowel syndrome (IBS). Importantly, this enteric population is susceptible to dietary intervention and represents an exciting target for the prevention and treatment of gut mediated disorders. This study will investigate microbial components and activities associated with the gut microbiome, using a global systems biology approach to explore the capacity of a human milk carbohydrate intervention in modulating this microbial community to target IBS, with the primary objective of improving IBS symptoms. IBS is a highly prevalent gastrointestinal (GI) disorder with significant negative impact on quality of life of patients and high healthcare costs. Although prognosis of IBS is benign, it is a disorder that poses a considerable burden on the individual sufferer and society. Patients typically present with chronic abdominal pain and an altered bowel habit, frequently accompanied by bloating and distension. Often, IBS will afflict sufferers for life, with flares of activity followed by periods of remission. Incidence commonly peaks in the third and fourth decades of life. IBS is suggested to be a disorder of gut-brain interaction, and alterations of the microbiota-host interactions at the mucosal border may cause symptoms such as those previously mentioned. Therefore, microbiota-targeted interventions may benefit some people with IBS by beneficially modulating the gut microbiome. Several studies have confirmed that prebiotics, such as galactooligosaccharides (GOS), are able to successfully stimulate gut bifidobacteria and alleviate symptoms in IBS. Prebiotics are defined as "a substrate that is selectively utilised by host microorganisms conferring a health benefit" \[8\]. These studies suggest that prebiotics may have potential as therapeutic agents in IBS. Breastmilk is known to play a crucial role in the development of infants, providing key nutrients and immunological compounds important for initial protection against pathogens \[9\]. Among these compounds, human milk oligosaccharides (HMOs) represent the third most important component of breastmilk after lipids and lactose. HMOs have also been investigated for potential health benefits in adults, including their potential role as prebiotics for improved gut microbiota modulation. Studies looking specifically at HMO interventions in humans with IBS are sparse. These include a phase II, parallel, RCT in 58 IBS volunteers by Iribarren et al. and an open-label trial with 245 IBS participants from 17 sites across USA by Palsson et al.. None have been sufficiently powered to a degree which could influence clinical practice, but crucially tolerability and safety profiles of HMOs investigated, to date, have been consistently high. Using the global systems biology approach not yet applied to this research question, a pre-competitive approach to selecting a candidate HMO, and a crossover feasibility trial design, the investigators hope to forge a new direction in establishing the merits of HMO use in IBS. This study will look specifically at patients with all IBS subtypes, an area where there is a real therapeutic gap and clinical need for safe, effective therapy to improve quality of life. Participants will be randomly allocated to be given either the HMO or a placebo, with neither the patient nor the researchers knowing which they are receiving (randomised and double blind design). They will take this HMO or placebo for 28 days (randomly distributed), and then stop taking it in a 'washout' period of 28 days, allowing the gut microbiota to return to baseline. Then, the participants will take the other intervention (placebo or prebiotic, whichever they did not take in the first half of the study) for 28 days, then have a further washout period of 14 days. The study will then be over. With this proposal, the aim is to explore how HMOs affect the gut microbiota and whether they can do so in a manner that positively influences patients with IBS. The investigators also hope to develop molecular profiling as part of a research toolkit for gut microbiome-based HMO supplement studies.

Conditions

Irritable Bowel Syndrome

Keywords

Gut microbiome; IBS; Human milk oligosaccharides

Outcome Measures

Primary Outcomes (1)

• IBS-SSS

  Irritable Bowel Syndrome Symptom Severity Score validated questionnaire. Each measure is rated from 0 to 100, with total scores ranging from 0 to 500.

  Clinically significant improvement in patient symptoms as defined by a decrease in IBS-symptom severity scoring over 16-week trial duration.

Secondary Outcomes (3)

• Change in anxiety and depression scores (ADS)

  Over 16-week trial duration.

• Improvement of the Pittsburgh Sleep Quality Index (PSQI).

  Over 16-week trial duration.

• Changes in faecal microbiota e.g. Bifidobacterium

  Over 16-week trial duration.

Study Arms (2)

Placebo control arm

PLACEBO COMPARATOR

Maltodextrin will be given as a white powder placebo for 4 weeks.

Dietary Supplement: Maltodextrin placebo

HMO intervention arm

EXPERIMENTAL

HMOs will be given as a white powder for 4 weeks.

Dietary Supplement: Human milk oligosaccharide

Interventions

Human milk oligosaccharide DIETARY_SUPPLEMENT

5g daily dose of HMOs.

Also known as: HMOs

HMO intervention arm

Maltodextrin placebo DIETARY_SUPPLEMENT

5g daily dose of maltodextrin.

Also known as: Placebo

Placebo control arm

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Signed consent form.
• Adults (aged from 18 to 60).
• Diagnosis of irritable bowel syndrome by a clinician (according to the Rome IV criteria).
• Absence of gut conditions other than IBS.

You may not qualify if:

• Intake of an experimental drug within four weeks prior to study.
• Former participation in prebiotic, probiotic or laxative trials within the previous four weeks.
• Former participation in a dietary intervention within the previous four weeks.
• Use of antibiotics within the previous four weeks.
• Intake of other specific prebiotics (such as oligosaccharides e.g. inulin), or probiotics (e.g. live yoghurts, other fermented products), drugs active on gastrointestinal motility, or a laxative of any class, for four weeks prior to study.
• Women who are lactating, pregnant or planning pregnancy during the study period.

Sponsors & Collaborators

• Glenn Gibson: lead
• Royal Berkshire NHS Foundation Trust: collaborator

Study Sites (1)

The University of Reading

Reading, Berkshire, RG6 6LA, United Kingdom

RECRUITING

Related Publications (1)

• Sanz Morales P, Wijeyesekera A, Robertson MD, Jackson PPJ, Gibson GR. The Potential Role of Human Milk Oligosaccharides in Irritable Bowel Syndrome. Microorganisms. 2022 Nov 25;10(12):2338. doi: 10.3390/microorganisms10122338.

  PMID: 36557589 BACKGROUND

MeSH Terms

Conditions

Irritable Bowel Syndrome

Condition Hierarchy (Ancestors)

Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Study Officials

• Glenn Gibson, Prof.

  The University of Reading

  STUDY DIRECTOR

Central Study Contacts

Patricia Sanz Morales

CONTACT

+447843865554; p.sanzmorales@pgr.reading.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Every individual involved in undertaking this trial will be blinded.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Food Microbiology

Model Details: This is a 16-week, randomised, placebo-controlled, double-blinded crossover trial. We aim to recruit 44 participants with IBS. These participants will be screened and classified into a particular IBS subtype. After a 14-day baseline period, participants will be randomised to orally consume either 5g of HMO for 28 days, or a placebo for 28 days. This will be administered at the University of Reading. All participants will then stop taking the product for 28 days (wash out period) and then swap treatment type and have 28 days of either placebo or HMO. This is then followed by another 14 days without any product. During the study, participants will be asked to complete a 24-hour food recall weeks 0 and 16. Additionally, participants will complete validated questionnaires (IBS-Symptom Severity Score, anxiety and depression score and Pittsburgh Sleep Quality Index (PSQI) every time they provide urine and faecal samples at each visit.

Study Record Dates

• First Submitted: February 19, 2024
• First Posted: February 28, 2024
• Study Start: February 20, 2024
• Primary Completion: August 20, 2025
• Study Completion: September 20, 2025
• Last Updated: February 29, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)