Clinical trial NCT06317441: The Safety And Efficacy Of A Probiotic Intervention On Lactulose Hydrogen Breath Test-Positive Patients And Related Gastrointestinal Symptoms
Official title: The Safety And Efficacy Of A Probiotic Intervention On Lactulose Hydrogen Breath Test-Positive Patients And Related Gastrointestinal Symptoms
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Small Intestinal Bacterial Overgrowth
SIBO
Keywords: Functional abdominal bloating and distension
Functional Diarrhea
Irritable Bowel Syndrome with Diarrhea
Irritable Bowel Syndrome
Abdominal Bloating
IBS
IBS-D
FABD
Functional Gastrointestinal Disorders
FGID
Lead sponsor: Nimble Science Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Lallemand Health Solutions
First posted: 2024-03-19
Enrollment: 105
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this study is to test the effect of a probiotic formulation on gastrointestinal symptoms, gut and small intestine microbiota in participants suffering from small intestinal bacterial overgrowth (SIBO). Two doses of probiotic will be evaluated against placebo.

Detailed description: The goal of this double-blinded, randomized, placebo-controlled clinical study is to evaluate whether two different doses of a probiotic formulation may have effect on gastrointestinal symptoms, as well as gut and small intestine microbiota, in participats suffering from SIBO. The two probiotic doses will be compared to a placebo.

The main research questions to be answered by this study are related to:

* Probiotic effect on bloating and abdominal distension.
* Probiotic effect on other gastrointestinal symptoms.
* Probiotic effect on incidence of SIBO.
* Probiotic effect on small intestine and gut microbiota.

The study will include a 2 month intervention with the investigational products and assessments will be conducted at baseline, mid-intervention, end-of-intervention, and follow-up period, with the exception of SIBO diagnosis, which will be conducted at baseline and at follow-up.

Eligibility criteria: Inclusion Criteria:

1. Aged 18-65 years old at the inclusion of the study, both female and male subjects.
2. Signed Informed Consent; willing and able to comply with study procedures.
3. Willing to maintain their diet and physical activity levels during the study.
4. Able to swallow a size-00 capsule (23mm length and 9mm width).
5. Participants with at least one of the following Rome IV diagnoses: FABD, functional diarrhea, IBS-M, or IBS-D.
6. Baseline weekly average of worst daily (in past 24 hours) abdominal bloating/distension score of \>= 3.0 on a 0-to-10-point scale.
7. Participants with abnormal LHBT following the North American Consensus recommendations (A rise in hydrogen of ≥20 ppm by 90 min).

Exclusion Criteria:

1. History of less than three (3) bowel movements per week.
2. With the diagnosis of IBS-C.
3. Prior gastrointestinal disease, surgery, or abdominal or pelvic radiation treatment which, in the Investigator's opinion, would lead to intestinal structuring or obstruction with a risk of capsule non-excretion, including, e.g., achalasia, eosinophilic esophagitis, any IBD, or previous esophageal, gastric, small intestinal, or colonic surgery. Appendectomy or cholecystectomy more than 3 months before the screening visit is acceptable.
4. Persons with central venous catheters.
5. History of known structural gastrointestinal abnormalities such as structures or fistulas leading to mechanical obstruction.
6. Known history abdominal radiation treatment.
7. Use of any medications in the week prior to the screening study visit, unless part of regular treatment, that could substantially alter gastrointestinal motor function (e.g., opioids, anticholinergics, or GLP-1 analogues); laxative use is allowed if used less than 3 times a week and it is willing to keep unchanged in the week prior to the SIMBA capsule ingestions. Proton pump inhibitors (PPIs) are allowed provided a wash-out period of 48 hours is respected before swallowing the SIMBA capsules and PPI treatment is resumed only 4 hours thereafter.

   o Prokinetic use. Potential participants who are not using prokinetics to treat SIBO may be eligible after a 2-week washout period, and willing to not use prokinetics for the study duration.
8. Unable to stop using laxatives or prokinetic medications for 4 days before the study procedure (BT). Laxatives can be resumed after the test is conducted.
9. Organic motility disorder, including gastroparesis, intestinal pseudo-obstruction, systemic sclerosis, Ogilvie's syndrome.
10. Celiac disease (treated or untreated).
11. Any significant heart, liver, lung, kidney, blood, endocrine or nervous system disease, which in the opinion of the investigator, would adversely affect study safety or outcome.
12. Cancer diagnosis or treatment within the past year (non-melanoma skin cancers are acceptable).
13. Gastrointestinal inflammatory diseases, including ulcerative colitis, Crohn's disease, microscopic colitis.
14. Participants with IBS presenting with alarm symptoms such as: rectal bleeding, unexplained weight loss, iron deficiency anemia, and nocturnal symptoms,
15. Participants over the age of 50 or older who have not had:

    * a colon cancer screening by either a negative FIT or FOBT test within the last 2 years; OR
    * a colonoscopy in the prior 10 years which was negative for colorectal cancer
16. Epilepsy diagnosis.
17. History or diagnosis of immunological diseases, infectious diseases or immune-compromised conditions, which in the opinion of the investigator, would adversely affect study safety or outcome. Such as, but not limited to, hepatitis, tuberculosis, HIV positive, Parkinson's, multiple sclerosis, AIDS, lymphoma, and long-term corticosteroid treatment.
18. History of oropharyngeal dysphagia, or other swallowing disorder with a risk of capsule aspiration.
19. Antibiotic use (except for topical use) ≤ 12 weeks prior to screening. Potential participants may be eligible once a 12-week washout is completed.
20. Regular use of probiotics, prebiotics or synbiotics (including food and drinks containing added probiotics and/or probiotic yogurts with live, active cultures) within 1 month prior to screening. Potential participants may be eligible once a 1-month washout is completed.
21. Any prior Fecal Microbiota Transplantation.
22. Pregnant or breastfeeding.
23. Planning to become pregnant.
24. Alcohol or drug abuse.
25. Allergy to the components present in the probiotic and placebo capsules.
26. Are non-English speaking.
27. Are scheduled for an MRI at any time during the study. Potential participants may be eligible to participate once their MRI procedure is completed.

Primary outcomes:
measure: Change in bloating/distension severity
timeFrame: From baseline to end of intervention (week 8).
Secondary outcomes:
measure: Median bloating-free days
timeFrame: Each intervention week and follow up (week 12) compared to baseline.
measure: Change in median bloating/distension severity
timeFrame: At all intervention weeks (with the exception of end-of-intervention, as described in the primary outcome) and follow-up (week 12) compared to baseline.
measure: Change in abdominal discomfort/pain
timeFrame: At mid-intervention (week 4), end of intervention (week 8), and follow-up (week 12) compared to baseline
measure: Changes in gastrointestinal symptoms
timeFrame: At mid-intervention (week 4), end of intervention (week 8), and follow-up (week 12) compared to baseline.
measure: Changes in stool frequency and consistency
timeFrame: At mid-intervention (week 4), end of intervention (week 8), and follow-up (week 12) compared to baseline.
measure: Changes in the quality of life
timeFrame: At mid-intervention (week 4), end of intervention (week 8), and follow-up (week 12) compared to baseline.
measure: Changes in reflux incidence and severity
timeFrame: At mid-intervention (week 4), end of intervention (week 8), and follow-up (week 12) compared to baseline.
measure: Changes in the severity of IBS symptoms
timeFrame: At mid-intervention (week 4), end of intervention (week 8), and follow-up (week 12) compared to baseline.
measure: Recovery rate of the probiotic strain
timeFrame: At mid-intervention (week 4) end of intervention (week 8), and follow-up (week 12) compared to baseline.
measure: Microbiome changes within small intestine, fecal and saliva samples
timeFrame: At mid-intervention (week 4), end of intervention (week 8), and follow-up (week 12) compared to baseline.
measure: Investigation how the microbiome and SIBO associate with each other though bacterial population analyses.
timeFrame: Through study completion, an average of 1 year
measure: Change in SIBO positivity rate
timeFrame: Through study completion, an average of 1 year
Other outcomes:
measure: Exploratory metabolomic analysis
timeFrame: Through study completion, an average of 1 year
measure: Exploratory: Quantifying the probiotic cell proportions
timeFrame: Through study completion, an average of 1 year
measure: Safety outcomes
timeFrame: Through study completion, an average of 1 year
Locations:
city: Calgary
country: Canada
facility: Nimble Science
state: Alberta
Study officials:
References: