Clinical trial NCT05205785: Human Milk Oligosaccharides (HMOs) for Irritable Bowel Syndrome (IBS)
Official title: Supporting Healthy Gastrointestinal Function With Human Milk Oligosaccharides (HMOs) in Individuals With Irritable Bowel Syndrome (IBS)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Irritable Bowel Syndrome
IBS - Irritable Bowel Syndrome
Keywords: Human Milk Oligosaccharides
HMOs
Lead sponsor: DSM Nutritional Products, Inc.
Sponsor class: INDUSTRY
First posted: 2022-01-25
Enrollment: 204
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: To assess the effects of a Human Milk Oligosaccharide mix given once daily for 12 weeks on stool consistency and abdominal pain compared to placebo in individuals with Irritable Bowel Syndrome (IBS).

Detailed description: HMO mix has been shown to provide therapeutic benefits to individuals with IBS of all subtypes (Palsson et al., 2019). DSM is planning this trial in order to investigate if clinically relevant improvements in bowel movements and IBS symptoms can be obtained through the use of the HMO mix in individuals with moderate to severe IBS and abdominal pain.

Eligible participants will have a diagnosis of Irritable Bowel Syndrome (IBS). Participants will be assessed for eligibility at the screening visit, must meet all the inclusion criteria, and none of the exclusion criteria.

In this trial, participants will be randomized to one of two intervention groups (a Human Milk Oligosaccharide mix or placebo) and receive intervention for at least 12 weeks.

Eligibility criteria: Inclusion Criteria:

1. Written informed consent obtained before any trial related assessments are performed.
2. Male or female aged ≥18 years at the time of consent.

   a. Female participants of child-bearing potential (females who are post-menopausal, i.e., when there has been no menstruation for a minimum of 12 months prior to screening, are considered not to be of child-bearing potential.), who are not surgically sterilized, must have a negative pregnancy test at screening and be willing to practice one of the following appropriate contraceptive methods until the last visit: i. Sexual abstinence. ii. Oral contraceptives. iii. Trans dermal patches or depot injection of a progestogen drug (starting at least 4 weeks prior to product administration). iv. Double barrier method: condom or occlusive cap (diaphragm or cervical/vault caps) plus spermicidal agent. v. Intrauterine device (IUD), intrauterine system (IUS), subdermal implant, or vaginal ring (placed at least 4 weeks prior to product administration). vi. Contraceptives must be effective before the randomization visit. However, national requirements should always be followed.
3. IBS-D or IBS-C or IBS-M according to Rome IV criteria. This will be established by using the IBS Module of the Rome IV Diagnostic Questionnaire, and requires recurrent abdominal pain on average at least 1 day per week during the previous 3 months that is associated with two or more of the following:

   1. Related to defecation (may be increased or unchanged by defecation) on at least 30% of pain instances in past 3 months.
   2. Associated with a change in stool frequency (on at least 30% of pain instances in past 3 months).
   3. Associated with a change in stool form or appearance (on at least 30% of pain instances in past 3 months).
4. Reported IBS diagnosis from a physician.
5. Personal access to the internet via computer, tablet, or smart-phone.
6. Be willing and able to comply with trial protocol, including entry of electronic diary data for at least 12 out of 14 diary days during the pre-randomization baseline 2-week run-in diary period (between V1 andV2).

   Inclusion criteria Visit 2: To be eligible for inclusion, the participant must fulfil all of the following criteria:
7. Scores of 1, 2, 6, or 7 on the Bristol stool scale at least twice per week \[as determined by eDiary completion between V1 and V2\].
8. An average baseline of worst abdominal pain of ≥3.3 (NRS-11) during the 2-week run-in period prior to randomization \[as determined by eDiary completion between V1 and V2\].

Exclusion Criteria:

The presence of any of the following criteria will exclude the participant from participating in the trial:

1. Treatment with an investigational drug from another clinical trial within 30 days/5 half- lives of the drug (which ever longest) prior to screening visit.
2. Any known gastrointestinal disease(s) or medical history that may interfere with the trial evaluations in the opinion of the investigator, in particular:

   1. Coeliac disease.
   2. IBD.
   3. Diverticulitis.
   4. C. difficile infection reported in the previous 2 years.
   5. Any clinically symptomatic biochemical or structural abnormality or active disease of the gastrointestinal tract within 6 months before screening, including daily diarrhea within two weeks prior to the screening interview or during the screening/baseline period.
   6. Substance abuse (within past 2 years).
   7. New use of antibiotics (within past 2 months), prebiotics, probiotics, or fiber supplements (within the past month).
   8. Hepatic dysfunction assessed as part of the blood safety panel (defined as alanine aminotransaminase/serum glutamic-pyruvic transaminase or aspartate aminotransaminase/serum glutamic-oxaloacetic transaminase \>2.5 x the upper limit of normal, or a history of hepatobiliary disease) or renal impairment (serum creatinine) \>2 mg/dl); any surgery (within a year of screening) on the stomach, small intestine, or colon (excluding appendectomy, hernia surgery not involving the GI tract, or c-section).
   9. Any history of pancreatitis (either acute or chronic).
   10. Laxative abuse (use of more than recommended dosage).
   11. Pregnant or lactating individuals.
   12. Any other gastrointestinal disease(s) or medical history that may interfere with the trial evaluations in the judgment of the investigator.
3. Following strict diets to improve their IBS symptoms as judged by the investigator e.g., Low FODMAP (within past 2 months). Exclusion based on diet will be reviewed by single investigator for consistency.
4. Any clinically relevant chronic disease(s) such as malignancy, diabetes, severe coronary disease, kidney disease, autoimmune or neurological disease, that in the opinion of the investigator would interfere with the trial evaluations or the safety of the participant.
5. Current severe psychiatric disease and/or psychological disturbance, a major psychiatric disorder requiring hospitalization in the last 3 years, or a history of attempted suicide or uncontrolled bipolar disorder; or clinical evidence of any significant psychiatric disease or symptoms that may interfere with the participant successfully completing the trial.
6. Treatment with restricted and prohibited concomitant medications.
7. Diagnosed with and treated for IBS for more than 10 years
8. Has a business or personal relationship with trial staff or sponsor who is directly involved with the conduct of the trial.
9. Lack of suitability for participation in the study for any reason as judged by the investigator.
10. Has previously been randomized into this trial, is participating in this trial at another investigational site or is planning to participate in any other clinical trial during this trial.
11. Desire and/or plans on changing current diet regime during the participation of this trial.

Primary outcomes:
measure: Absolute change in the proportion of stools with abnormal fecal consistency in the active product compared to placebo group.
timeFrame: Baseline (2 week run in period) to end of intervention (weeks 11 + week 12)
measure: Absolute change in the pain severity score (IBS-SSS) in the active product compared to placebo group.
timeFrame: Baseline (Visit 2) to Week 12 (Visit 3)
Secondary outcomes:
measure: Absolute change in total IBS severity score in the active product compared to placebo group.
timeFrame: Baseline (Visit 2) to Week 12 (Visit 3)
measure: Absolute change in total IBS Quality of Life (IBS-QOL) score in the active product compared to placebo group.
timeFrame: Baseline (Visit 2) to Week 12 (Visit 3)
measure: Relative change in abundance of fecal Bifidobacteria spp in the active product compared to placebo group.
timeFrame: Baseline (Visit 2) to Week 12 (Visit 3)
Other outcomes:
measure: Absolute change in GSRS-IBS (Gastrointestinal Symptom Rating Scale-IBS) scores.
timeFrame: Baseline (Visit 2) to Week 12 (Visit 3)
measure: Abdominal pain responder rate.
timeFrame: Baseline (2-week run-in period) to the last two weeks of intervention (week 11+12)
measure: Absolute change in BSFS (Bristol Stool Form Scale) score.
timeFrame: Baseline (2-week run-in period) to the last two weeks of intervention (week 11+12)
measure: Absolute change in the number (or frequency) of bowel movements.
timeFrame: Baseline (2-week run-in period) to the last two weeks of intervention (week 11+12)
measure: Percentage of participants with a decrease of 50 points in total IBS-SSS score.
timeFrame: Baseline (Visit 2) to Week 12 (Visit 3)
measure: Absolute change in GAD-7 score.
timeFrame: Baseline (Visit 2) to Week 12 (Visit 3)
measure: Absolute change in PHQ-8 score.
timeFrame: Baseline (Visit 2) to Week 12 (Visit 3)
measure: Absolute change in WPAI-IBS (Work Productivity and Activity Impairment-IBS) score.
timeFrame: Baseline (Visit 2) to Week 12 (Visit 3)
measure: Absolute change in BIPQ score.
timeFrame: Baseline (Visit 2) to Week 12 (Visit 3)
measure: Absolute change in total IBS-SSS score and individual scores.
timeFrame: Baseline (Visit 2) to week 4 (call 1), to week 8 (call 2), and to week 12 (Visit 3)
measure: Absolute change in the use of medications and treatments for bowel habits.
timeFrame: Baseline (2-week run-in period) to the last two weeks of intervention (week 11+12).
measure: Adverse Events by product causality
timeFrame: Baseline (Visit 2) to Week 12 (Visit 3)
measure: Incidence of mild, moderate, and severe AEs
timeFrame: Baseline (Visit 2) to Week 12 (Visit 3)
measure: Severe Adverse Events (SAEs) by product causality
timeFrame: Baseline (Visit 2) to Week 12 (Visit 3)
measure: Vitals I
timeFrame: Baseline (Visit 2) to Week 12 (Visit 3)
measure: Vitals II
timeFrame: Baseline (Visit 2) to Week 12 (Visit 3)
measure: Vitals III
timeFrame: Baseline (Visit 2) to Week 12 (Visit 3)
measure: Vitals IV
timeFrame: Baseline (Visit 2) to Week 12 (Visit 3)
measure: Safety Labs
timeFrame: Baseline (Visit 2) to Week 12 (Visit 3)
measure: Urinalysis (pH, protein, glucose, ketone, urobilinogen, bilirubin, blood, and nitrite).
timeFrame: Baseline (Visit 2) to Week 12 (Visit 3)
Locations:
city: Cork
country: Ireland
facility: Atlantia Clinical Trials Ltd
state: Cork/Munster
Study officials:
affiliation: Atlantia Clinical Trials
name: Martin Buckley, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: DSM
name: Seema Mody, MSc
role: STUDY_DIRECTOR
References: