GOS to Reduce Symptom Severity in IBS

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

Inclusion criteria

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

Exclusion criteria

• Unclassifiable IBS (IBS-U) as determined by Investigator
• 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.

• Systemic antibiotic or antimycotic treatment within 4 weeks prior to study entry
• Use of laxatives or antidiarrheal medication within 1 week prior to study entry
• 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).
• 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.
• 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.
• Galactosemia (galactose metabolism disorder)
• 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).

• 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.

• 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
• 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

• Recent unintended weight loss:

o >5% of total body weight within 6 months prior to study entry

• Excessive alcohol consumption (>14 units per week) and/or drug abuse
• Pregnancy and lactation, or plan to become pregnant during the study period
• Participation in other studies involving investigational or marketed products concomitantly or within 3 months prior to study entry
• 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.