Determination of the Safety and Efficacy of Two Probiotic Strains (CODECS)

Determination of the Safety and Efficacy of Two Probiotic Strains in Adults With Mild to Moderate Gastrointestinal Discomfort

The goal of this study is to determine the safety and efficacy of two probiotic strains in adults with mild to moderate gastrointestinal discomfort. The main questions it aims to answer is whether 6-week administration of a probiotic can improve how the participant feels regarding their gut health. This is done by completing a weekly questionnaire and the results are compared between the 6 weeks the participants are on a placebo and the 6 weeks the participants are on the probiotic. Participants will also provide a blood sample, and stool sample at the start and end of each treatment. Similarly, the results from the blood samples and stool samples will be analysed to determine if there is any improvement in markers related to gut health.

Study Overview

• Status: Not yet recruiting
• Conditions: Gastrointestinal Dysfunction
• Intervention / Treatment: Dietary supplement: Placebo 1 to Probiotic A; Dietary supplement: Placebo 2 to Probiotic B; Dietary supplement: Probiotic A to Placebo 1; Dietary supplement: Probiotic B to Placebo 2

Detailed Description

In this randomized, crossover, double-blind, prospective, placebo controlled study we aim to determine the safety and efficacy of two probiotic strains in adults with mild to moderate gastrointestinal discomfort. 100 healthy adults with subclinical mild to moderate gastrointestinal complaints (GSRS-IBS score 20-45 inclusive), 50 subjects per strain (test sequence). The GSRS-IBS (gastrointestinal symptom rating scale - irritable bowel syndrome) questionnaire ranges from 0-78 with a greater score indicating a higher occurrence of gastrointestinal symptoms. Safety: To evaluate adverse events that occur during the probiotic treatment period as compared to the placebo period. Incidence and duration of upper respiratory tract symptoms, urinary tract symptoms, gastrointestinal symptoms as primary outputs. Efficacy: To evaluate the effect of 6-week probiotic administration on gastrointestinal homeostasis using GSRS-IBS score as an index as compared to placebo. Following a screening period, participants will provide stool, urine (safety) and blood samples prior to commencing a 6 week course of either placebo or one of the probiotics. At this time participants will again provide blood and stool samples. Throughout the study participants will maintain a daily diary to note any unusual events and to report stool consistency using Bristol stool chart. The participants will also complete a once-weekly questionnaire (GSRS-IBS questionnaire) relating to gut health. There will then be a 3-week washout period where they will take no products. After these 3 weeks the participants will again provide a stool and blood samples, and as before maintain their daily diary and weekly questionnaire for 6 weeks while on the probiotic or placebo (they will have swapped at this point). After these 6 weeks the participants will again provide stool and blood samples.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Signed Informed consent form
2. Healthy adults aged 18-65 years
3. Subclinical mild to moderate gastrointestinal complaints (GSRS-IBS score 20-45 at baseline)

Exclusion Criteria:

1. Presence of a serious congenital anomaly or chronic medical condition that would contraindicate participation, including history of major gastrointestinal surgery, chronic gastrointestinal illness, abnormal intestinal anatomy or significant abdominal disorder
2. Severe chronic illnesses
3. Known immunodeficiency
4. Use of immunosuppressive agents (corticosteroids, methotrexate…)
5. Presence of severe immunodeficient family members as provided by subjects self-report
6. Pregnancy, 6 months postpartum period or current breastfeeding
7. Women of childbearing age planning pregnancy during the course of the study
8. Actively participating in another clinical study, having completed a clinical study in the past 60 days or being in the exclusion period of a previous clinical study
9. Not able to understand and comply with requirements of the study
10. Use of probiotics, prebiotics, postbiotics, antibiotics within 3 weeks of study commencement

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Placebo 1 to Probiotic A; Sequence A1 (n=25): Placebo 1 administered daily for 42 days, followed by 21 days washout, then 1 x 10^9 colony forming units (CFU) of Probiotic A administered daily for 42 days	Dietary supplement: Placebo 1 to Probiotic A; 42 day Crossover study design between Placebo 1 and Probiotic A (n = 25)
Active Comparator: Placebo 2 to Probiotic B; Sequence B1 (n=25): Placebo 2 administered daily for 42 days, followed by 21 days washout and 42 days Probiotic formula: containing 1 x 10^9 CFU of Probiotic B administered daily	Dietary supplement: Placebo 2 to Probiotic B; 42 day Crossover study design between Placebo 2 and Probiotic B (n = 25)
Active Comparator: Probiotic A to Placebo 1; Sequence A2 (n=25): 1 x 10^9 CFU of Probiotic A administered daily for 42 days, followed by 21 days washout, then Placebo 1 administered daily for 42 days	Dietary supplement: Probiotic A to Placebo 1; 42 day Crossover study design between Probiotic A and Placebo 1 (n = 25)
Active Comparator: Probiotic B to Placebo 2; Sequence B2 (n=25): 1 x 10^9 CFU of Probiotic B administered daily for 42 days, followed by 21 days washout and 42 days Placebo 2 administered daily for 42 days	Dietary supplement: Probiotic B to Placebo 2; 42 day Crossover study design between Probiotic B and Placebo 2 (n = 25)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in GSRS-IBS score	Change in the GSRS-IBS score while participants are on the treatment as compared with placebo. GSRS-IBS ranges from 0-78 with a greater score indicating a higher occurence of gastrointestinal symptoms	Baseline vs Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of upper respiratory tract symptoms	Incidence of upper respiratory tract symptoms, as captured by incidence of upper respiratory tract as reported by clinician/PI	Baseline vs Week 6
Duration of upper respiratory tract symptoms	Duration of upper respiratory tract symptoms, as captured by duration of upper respiratory tract as reported by clinician/PI	Baseline vs Week 6
Incidence of urinary tract infections	Incidence of urinary tract infections, as captured by incidence of urinary tract infections as reported by clinician/PI	Baseline vs Week 6
Duration of urinary tract infections	Duration of urinary tract infections, as captured by duration of urinary tract infections as reported by clinician/PI	Baseline vs Week 6

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Stool consistency	To evaluate the difference in stool consistency as determined by daily Bristol stool chart scale captured in daily diary. The Bristol stool chart ranges from 1-7, with 1,2 being hard and solid and 6,7 being loose and watery. This readout will be the change in stool consistency towards types 3,4 and 5	Baseline vs Week 6
Questionnaire regarding general health	General health questionnaire regarding mood, sleep, energy, concentration and changes in appetite. This is based on a Likert scale ranging from 0 (no effect) to 7 (severe)	Baseline vs Week 6
Changes in microbiome readouts	To determine if there are any changes in alpha and beta diversity in the microbiome using 16S rRNA sequencing ( a common methodology used in assessing microbiome readouts) between placebo and probiotic treatment.	Baseline vs Week 6
Changes in blood immune biomarkers	To determine if there are any changes in biomarkers relating to immune markers including IL-6 (IL interleukin), IL-10, TNFalpha, IFNgamma in pg/mL serum.	Baseline vs Week 6
Regularity of defecation	Regularity of defecation as captured by daily diary	Baseline vs Week 6
Changes in serum short chain fatty acid levels	Changes in serum short chain fatty acids (SCFA's) including acetate, propionate and butyrate in micromol/L)	Baseline vs Week 6
Changes in serum amino acids levels	Changes in serum amino acids levels including the essential amino acids histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine; and the non-essential amino acids alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, proline, serine, and tyrosine in micromol/L	Baseline vs Week 6

Collaborators and Investigators

• Sponsor: The Archer-Daniels-Midland Company
• Collaborators: Merieux NutriSciences (China)

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: May 16, 2024
• First Submitted That Met QC Criteria: June 17, 2024
• First Posted (Actual): June 20, 2024

Study Record Updates

• Last Update Posted (Actual): June 20, 2024
• Last Update Submitted That Met QC Criteria: June 17, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: probiotic; gastrointestinal discomfort
• Other Study ID Numbers: PCTB202108

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No