Clinical trial NCT05157061: GOS to Reduce Symptom Severity in IBS
Official title: A Multi-centre, Randomized, Placebo-Controlled, Efficacy Study of Prebiotic Galacto-oligosaccharides on Gastrointestinal Symptom Severity in Patients With Irritable Bowel Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Irritable Bowel Syndrome
Irritable Bowel Syndrome - Constipation
Irritable Bowel Syndrome - Diarrhoea
Irritable Bowel Syndrome - Mixed
Keywords: Irritable Bowel Syndrome
Diarrhoea
Constipation
Galacto-oligosaccharides (GOS)
Symptom severity
Prebiotic
Supplement
Rome IV Criteria
Lead sponsor: Clasado
Sponsor class: INDUSTRY
Collaborators: name: CR2O B.V.
First posted: 2021-12-14
Enrollment: 153
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase III, randomized, double-blind, placebo-controlled, multi-centre, 8-week intervention study, preceded by a 2-week run-in period, to assess the efficacy of GOS on symptom severity in adult patients with IBS.
Primary purpose: TREATMENT

Brief summary: IBS is a highly prevalent bowel disorder, characterized by recurrent abdominal pain during bowel movements or a change in bowel habits. Typically, IBS patients experience constipation, diarrhoea or a mix of constipation and diarrhoea, as well as symptoms of abdominal bloating or distension. The chronic and bothersome nature of IBS symptoms negatively affects the quality of life of many patients. Because there are currently limited medical treatment options for IBS, it is important to study new treatments.

IBS can (in part) be caused by an 'imbalance' of the bacteria residing in the intestinal tract. For instance, there may be a lower proportion of specific bacteria that are generally considered beneficial for a persons health. The consumption of non-digestible food ingredients, such as GOS, may stimulate the growth of these beneficial bacteria. GOS is a type of 'prebiotic', which is known to support health and wellbeing of consumers. By restoring the bacterial balance of the intestinal tract, the symptoms of IBS may be reduced after consumption of GOS.

The health effects of the study product (a specific GOS) used in current study was previously investigated in a small group of patients with IBS. Use of the study product indicated a reduction in the patients' symptoms, improvement in the patients' quality of life, and changes in patients' gut bacteria. It is therefore hypothesized that GOS / a specific GOS may reduce the symptom severity of patients with IBS.

This study further evaluates how GOS may improve symptoms of IBS.

Detailed description: A Phase III, randomized, double-blind, placebo-controlled, multi-centre, 8-week intervention study, preceded by a 2-week run-in period, to assess the efficacy of GOS on symptom severity in adult patients with IBS. The study population will consist of 210 adult patients diagnosed in the past 36 months with IBS-Diarrhoea (N =70), IBS-Constipation (N = 70), or IBS-Mixed (N =70).

Irritable bowel syndrome (IBS) is a highly prevalent and multifaceted functional bowel disorder characterized by recurrent abdominal pain associated with defecation or a change in bowel habits in the absence of detectable structural and biochemical abnormalities. Disordered bowel habits are typically present, such as constipation, diarrhoea or a mix of constipation and diarrhoea, as are symptoms of abdominal bloating/distension. The chronic and bothersome nature of IBS symptoms negatively affects patients' quality of life and introduces a substantial economic burden on patients and the healthcare system. The gut microbiota composition and function may play a pivotal role in the pathogenesis of IBS, as a reduction in endogenous bifidobacteria, lactobacilli, and Faecalibacterium prausnitzii concentrations, as well as small bowel bacterial overgrowth have been reported in IBS patients, thereby introducing the gut microbiota as a potential target for treatment and symptom relief. Intervention with non-digestible food ingredients, such as galacto-oligosaccharides (GOS), may form a suitable intervention strategy, as these 'prebiotics' are known to modulate the gastrointestinal (GI) microbiota and support health and wellbeing of the host.

The safety and efficacy of GOS has previously been evaluated in patients with IBS, which demonstrated that GOS may reduce IBS symptom severity, improve quality of life, improve stool consistency and defecation frequency and alter gut microbiota composition, in a safe manner.

As there are currently limited suitable medical treatments for IBS, this study will evaluate the efficacy of GOS in reducing symptom severity of patients with IBS

Eligibility criteria: Inclusion Criteria:

1. Patients who have been diagnosed with IBS by a medically trained person/Health Care Professional (HCP).
2. IBS diagnosis to be confirmed according to the Rome-IV criteria by a primary or secondary care clinician, including a gastroenterologist, at study entry
3. An IBS Symptom Severity Scale score of ≥125 points at baseline
4. Male or female between 18 and 64 years of age (age ranges included)
5. Possession of a smartphone
6. Willing and eligible to provide consent and comply with protocol and product intake.

Exclusion Criteria:

1. Unclassifiable IBS (IBS-U) as determined by Investigator
2. Use of products marketed as prebiotics, probiotics or synbiotics within 4 weeks prior to study entry (e.g. Yakult, Actimel, Activia, VSL#3, Kefir).

   o Regular cheese or yogurt containing lactic acid bacteria are not an exclusion criterion.
3. Systemic antibiotic or antimycotic treatment within 4 weeks prior to study entry
4. Use of laxatives or antidiarrheal medication within 1 week prior to study entry
5. An unstable antidepressant/antipsychotic treatment regimen within 3 months prior to study entry (i.e. treatment should be stable for at least 3 months prior to study entry).
6. Confirmed lactose intolerance, defined as patients who report response to dietary elimination of lactose/dairy products. Confirmation is patient-reported and not done within the scope of this study.
7. Confirmed food allergy, with reported confirmation based on OFC, IgE, or skin prick test. Confirmation is patient-reported and not done within the scope of this study.
8. Galactosemia (galactose metabolism disorder)
9. Following diets likely to affect study outcomes, including:

   o low FODMAP, KETO/high-fat, gluten free/coeliac, paleo, weight loss, caloric restriction, low-carb, 5:2/whole day energy restriction, Atkins/high-protein, sugar-free, single-food, juicing/any day of juicing, any other restriction diet (e.g. very low calory), or vegan diets (GOS is derived from cow's milk).
10. Severe illness(es) or medical condition(s), including gastrointestinal pathologies:

    o GI ulcers, coeliac disease, inflammatory bowel disease, bowel cancer, bowel resection, , bariatric surgery, acute or chronic diarrhoea secondary to confirmed infectious gastroenteritis, or enteral or parenteral nutrition.
11. Subjects suffering from auto-immune disorders (e.g. Rheumatoid Arthritis, Systemic lupus erythematosus, Multiple Sclerosis, Graves' Disease) that require treatment with an immune modulator treatment or anti-inflammatory medication
12. Surgical operations to the mouth or gastrointestinal tract within 4 weeks prior to study entry, or planned during the study

    o Appendectomy within 6 months prior to study entry
13. Recent unintended weight loss:

    o \>5% of total body weight within 6 months prior to study entry
14. Excessive alcohol consumption (\>14 units per week) and/or drug abuse
15. Pregnancy and lactation, or plan to become pregnant during the study period
16. Participation in other studies involving investigational or marketed products concomitantly or within 3 months prior to study entry
17. Changes in diet, supplement or medication use likely to affect study outcomes (i.e. medication that influences GI function) within 4 weeks prior to study entry or planned during the study (at the discretion of the Investigator). For example, the following medications will influence GI function and changes must be avoided: opioids, prokinetics (domperidone, metoclopramide, prucalopride), antispasmodics (peppermint oil, buscopan), and acid suppressants (PPI, H2 blockers). Of note: the intake of fibres (e.g. psyllium husk) may be used provided that the participant has been using this as a supplement for more than 4 weeks prior to study participation and intake does not change during the course of participation.

Primary outcomes:
measure: IBS symptom Severity
timeFrame: Baseline to end of the study (Day 56).
Secondary outcomes:
measure: Abdominal pain
timeFrame: During the intervention period (8 weeks)
measure: Bloating.
timeFrame: During the intervention period (8 weeks)
measure: Global IBS improvement
timeFrame: During the intervention period (8 weeks)
measure: Stool consistency
timeFrame: During the intervention period (8 weeks)
measure: Defecation frequency
timeFrame: During the intervention period (8 weeks)
measure: Quality of Life IBS-QOL score
timeFrame: At the end of the study (Day 56)
measure: Anxiety and depression
timeFrame: At the end of the study (Day 56)
measure: Nature, incidence, frequency, severity of adverse events/serious adverse events and relationship to the study intervention.
timeFrame: During the intervention period (8 weeks)
measure: Rescue medication
timeFrame: From screening to end of intervention period (10 weeks)
Other outcomes:
measure: Immune function
timeFrame: At the end of the study (Day 56).
measure: Gut microbiome composition
timeFrame: At the end of the study (Day 56).
measure: Blood metabolites
timeFrame: At the end of the study (Day 56).
measure: Correlation between blood metabolites and gut microbiome
timeFrame: At the end of the study (Day 56).
measure: Correlation between gut microbiome and mean composite IBS-Symptom Severity Scores
timeFrame: At the end of the study (Day 56).
Locations:
city: Leuven
country: Belgium
facility: University Hospital Leuven location Gasthuisberg
city: Leeuwarden
country: Netherlands
facility: Medisch Centrum Leeuwarden (MCL)
state: Friesland
city: 's-Hertogenbosch
country: Netherlands
facility: Jeroen Bosch Ziekenhuis, Gastroenterology department
state: Noord-Brabant
city: Ede
country: Netherlands
facility: Ziekenhuis Gelderse Vallei, Afdeling Maag-Darm-Leverziekten
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospital NHS Trust in association with the University of Leeds
state: North Yorkshire
city: Durham
country: United Kingdom
facility: County Durham &amp;Darlington NHS Foundation trust, University Hospital of North Durham
city: London
country: United Kingdom
facility: Barts Health NHS Trust, Wingate Clinical Trials Facility
city: Manchester
country: United Kingdom
facility: Manchester University NHS Foundation Trust, Wythenshawe Hospital, Neurogastroenterology Unit
city: Newcastle Upon Tyne
country: United Kingdom
facility: NIHR National Patient Recruitment Centre Newcastle
Study officials:
affiliation: Clasado Research Services Limited
name: Lucien F. Harthoorn, PhD.
role: STUDY_DIRECTOR
References: