Clinical trial NCT02875847: Effects of HMOs on Faecal Microbiota, Gastrointestinal Symptoms, Mucosal Immunity and Barrier Function in IBS Patients
Official title: The Effects of Human Milk Oligosaccharides on Faecal Microbiota, Gastrointestinal Symptoms, Mucosal Immunity and Barrier Function in Irritable Bowel Syndrome: a Parellell, Double-blind, Randomised, Placebo-controlled Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Irritable Bowel Syndrome (IBS)
Lead sponsor: Glycom A/S
Sponsor class: INDUSTRY
Collaborators: name: Sahlgrenska University Hospital
First posted: 2016-08-23
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study is a randomised, placebo-controlled, double-blind parallel study in IBS patients. A total of 60 adult patients diagnosed with IBS-C, -D or -A/M according to Rome IV criteria will be included. The participants will be randomized into one of three groups consuming either HMO (two groups) or placebo (one group).

The primary objective of the study is to establish the effect of HMOs on the faecal microbiota in IBS patients. Secondary objectives are to assess the effect on gastrointestinal symptoms, mucosal immunity, gut barrier function, quality of life, and anxiety and depression.


Eligibility criteria: Inclusion Criteria:

1. Signed written informed consent
2. Age between 18 and 75 years at visit 2
3. Fulfills definition of IBS-D, IBS-C or IBS-A/M according to Rome IV criteria
4. Have a global IBS-SSS score of \>174 during the 2 weeks run-in period
5. Read, speak and understand Swedish
6. Ability and willingness to understand and comply with the study procedures

Exclusion Criteria:

1. Participation in a clinical intervention trial one month prior to screening visit and throughout the study.
2. Any known gastrointestinal disease(s) that may cause symptoms or may interfere with the trial outcome, as judged by the investigator; in particular

   * lactose intolerance
   * coeliac disease
3. Other severe disease(s) such as malignancy, diabetes, severe coronary disease, kidney disease or neurological disease, as judged by the investigator.
4. Severe psychiatric disease and/or psychological disturbance, as judged by the investigator.
5. Use of highly dosed probiotic supplements (yoghurt allowed) one month prior to the study and throughout the study. Excluded products are (i) probiotic supplements in the form of capsules, tablets, and powders in sachets, and (ii) probiotic food and drink products which contain high doses of probiotics. The excluded food and drink products are available in the form of yoghurts, drinking yoghurts, shots and drinks under brands such as Proviva, Actimel, Activia, Wellness, and Verum.
6. Consumption of antibiotic drugs one month prior to screening and throughout the study. Antibiotic use within the last three months prior to screening will be registered.
7. Consumption on a regular basis of medication that might interfere with symptom evaluation (as judged by the investigator) two weeks prior to screening and throughout the study. Specifically excluded drugs are opioids, NSAIDs on a weekly basis, regular use of laxatives and anti-diarrhoeal drugs, any drugs indicated for IBS symptoms.
8. Diagnosed with and treated for IBS for more than 10 years
9. Pregnant or lactating or wish to become pregnant during the period of the study.
10. Lack of suitability for participation in the study for any reason as judged by the investigator.

Primary outcomes:
measure: Change from baseline in intestinal bifidobacteria abundance
timeFrame: Baseline and after 4 weeks of intake
Secondary outcomes:
measure: Change from baseline of faecal microbiota profile
timeFrame: Baseline and after 4 weeks of intake, and after 4 weeks of wash-out
measure: Change from baseline of IBS symptoms as measured via the total score on the IBS Symptoms Severity Scale (IBS-SSS) and the proportion of responders in all patients and subgroup of patients
timeFrame: Baseline and after 4 weeks of intake, and after 4 weeks of wash-out
measure: Change from baseline of intensity of abdominal pain and number of days of abdominal pain as measured on the 11 point Numeric Rating Scale (NRS-11) in all patients and subgroups of patients
timeFrame: Baseline and after 4 weeks of intake, and after 4 weeks of wash-out
measure: Change from baseline of bowel habits as measured via the IBS-SSS, the Bristol Stool Form Scale (BSFS) and a bowel movement diary in all patients and subgroup of patients
timeFrame: Baseline and after 4 weeks of intake, and after 4 weeks of wash-out
measure: Change from baseline of abdominal distention as measured via the IBS-SSS in all patients and subgroups of patients
timeFrame: Baseline and after 4 weeks of intake, and after 4 weeks of wash-out
measure: Change from baseline of gastrointestinal symptoms as measured by the Gastrointestinal Symptom Rating Scale for IBS patients (GSRS-IBS) in all patients and subgroup of patients
timeFrame: Baseline and after 4 weeks of intake, and after 4 weeks of wash-out
measure: Change from baseline of quality of life in IBS patients as measured by the IBS-QOL in all patients and subgroups of patients
timeFrame: Baseline and after 4 weeks of intake, and after 4 weeks of wash-out
measure: Change from baseline of anxiety and depression as measured by the Hospital Anxiety and Depression Scales (HADS) in all patients and subgroups of patients
timeFrame: Baseline and after 4 weeks of intake, and after 4 weeks of wash-out
measure: Change from baseline of gastrointestinal symptom specific anxiety as measured by the Visceral Sensitivity Index (VSI) in all patients and subgroup of patients
timeFrame: Baseline and after 4 weeks of intake, and after 4 weeks of wash-out
measure: Change from baseline of severity of somatic symptoms as measured by the Patient Health Questionnaire-15 (PHQ-15) in all patients and subgroup of patients
timeFrame: Baseline and after 4 weeks of intake, and after 4 weeks of wash-out
measure: Change from baseline of biomarkers of inflammation in all patients and subgroups of patients
timeFrame: Baseline and after 4 weeks of intake, and after 4 weeks of wash-out
measure: Change from baseline of biomarkers of gut barrier function in all patients and subgroups of patients
timeFrame: Baseline and after 4 weeks of intake, and after 4 weeks of wash-out
measure: Change from baseline of biomarkers of the gut-brain axis in all patients and subgroups of patients
timeFrame: Baseline and after 4 weeks of intake, and after 4 weeks of wash-out
Other outcomes:
Locations:
city: Göteborg
country: Sweden
facility: SU Sahlgrenska, Department of Internal Medicine
Study officials:
affiliation: Department of Internal Medicine
name: Magnus Simrén, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Internal Medicine
name: Hans Törnblom, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Internal Medicine
name: Lena Öhman, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Iribarren C, Tornblom H, Aziz I, Magnusson MK, Sundin J, Vigsnaes LK, Amundsen ID, McConnell B, Seitzberg D, Ohman L, Simren M. Human milk oligosaccharide supplementation in irritable bowel syndrome patients: A parallel, randomized, double-blind, placebo-controlled study. Neurogastroenterol Motil. 2020 Oct;32(10):e13920. doi: 10.1111/nmo.13920. Epub 2020 Jun 14.