Safety and Tolerance of a Novel Three-Strain Probiotic in Healthy Adults

A Two-Phase Study on the Safety and Tolerance of a Novel Probiotic in Healthy Adults: Open-Label and Double-Blind, Placebo-Controlled Study

This Phase I & II study evaluates the safety and tolerability of 8 weeks of daily supplementation with high-dose versus standard-dose of a novel three-strain probiotic. Safety and tolerability will be assessed by adverse events, safety blood profile, and vital signs. Secondary assessments include food cravings, gastrointestinal outcomes, sleep, quality of life, subjective ratings of hunger and satiety and associated hormone responses including plasma GLP-1, glucose, and insulin.

Study Overview

• Status: Active, not recruiting
• Conditions: Healthy Adults
• Intervention / Treatment: Dietary supplement: Three-Strain Probiotic; Dietary supplement: Phase 2 - Placebo

Detailed Description

A Two-Phase Study safety and tolerance study:

Phase I: Open-Label Study Phase II: Randomised Double-Blind, Placebo-Controlled Study

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Ireland
  • Cork, Ireland
    • Atlantia Clinical Trials

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

To be eligible for inclusion, the Participant must fulfill all the following criteria:

1. Be able to give written informed consent.
2. Be between 18 and 65 years, inclusive.
3. Has a BMI: Phase I ≤29.9kg/m2. Phase II ≤34.9kg/m2.
4. Mean total food craving score (FCI-UK) of ≥2.5 at screening visit. (Phase I only) 5. Stable weight for the past 30 days (defined as ± 2.3kg).

6. Willing to consume the Study Product daily for the duration of the study.

Exclusion Criteria:

Participants will be excluded from the study if they meet any of the following criteria:

1. Participants who are pregnant or wish to become pregnant during the study or who are lactating and/or currently breastfeeding.

2. Participants currently of biological childbearing potential, but not using a continuous effective method of contraception, as outlined below:

   1. Complete abstinence from intercourse two weeks prior to administration of the Study Product, throughout the clinical study, until the completion of follow-up procedures or for two weeks following discontinuation of the Study Product in cases where Participant discontinues the study prematurely. (Participants utilising this method must agree to use an alternate method of contraception if they should become sexually active and will be queried on whether they have been abstinent in the preceding two weeks when they present to the clinic for the final visit).
   2. Has a male sexual partner who is surgically sterilised prior to the Screening Visit and is the only male sexual partner for that Participant.
   3. Sexual partner(s) is/are exclusively female.
   4. Use of acceptable method of contraception, such as a spermicide, mechanical barrier (e.g., male condom, female diaphragm), tubal ligation, or contraceptive pill. The Participant must be using this method for at least one week prior to and one week following the end of the study.
   5. Use of any intrauterine device (IUD) or contraceptive implant. The Participant must have the device inserted at least two weeks prior to the first screening visit, throughout the study, and two weeks following the end of the study.

3. Has food allergies or other issues with foods that would preclude intake of the Study Products.

   1. Known hypersensitivity to any component of the probiotic used in the study (Clostridium butyricum WB-STR-0006, Akkermansia muciniphila WB-STR-0001, Bifidobacterium infantis, chicory inulin, microcrystalline cellulose, l-leucine, hypromellose (vegetarian capsule), silica)
   2. Known hypersensitivity or allergy to any component of the meal product used in the meal challenge (allergens: milk and soy)
4. Has any significant acute or chronic coexisting health conditions that would prevent them from fulfilling the study requirements, put the Participant at risk or would confound the interpretation of the study results as judged by the investigator on the basis of medical history and routine laboratory test results. Excluded health conditions include: a. Gastrointestinal condition (including GI bleeding in the past 3 months) b. Major gastrointestinal surgery or explorations (cholecystectomy and appendectomy are allowed) c. Cancer (in the past 1 year) d. Active autoimmune condition e. Cardiovascular disease (in the past 3 months) 5. Current or recent use of a medication that the investigator believes would interfere with the objectives of the study or pose a safety risk or confound the interpretation of the study results. Prohibited medications include: a. Oral antibiotics or Antifungals (in the past 1 month) b. Medications impacting gut motility (in the 2 weeks prior to baseline) c. GLP-1 receptor agonists (in the past 6 months) d. Sulfonylureas (in the past 6 months) e. Proton Pump Inhibitors (in the past 1 month) f. Laxatives (in the past 1 month)

6. Current or recent (in the past 1 month) use of prohibited nutritional or non-nutritional supplements, including:

1. Probiotics/Prebiotics

2. Fibre supplements 7. Individuals who, in the opinion of the investigator, are considered to be poor attendees or unlikely for any reason to be able to comply with the study.

   8. Participants may not be receiving treatment involving experimental drugs/supplements. If the Participant has been in a recent experimental study, these must have been completed not less than 90 days for drugs and 30 days for supplements prior to this study.

   9. Current participation or planned participation in a weight loss program during the study period 10. Known hypersensitivity to >4 first-line antimicrobial therapies against Akkermansia muciniphila: Penicillin, Piperacillin, Amoxicillin, Ampicillin, Tetracycline 11. Known hypersensitivity to >4 first-line antimicrobial therapies against Clostridium butyricum: Penicillin, Piperacillin, Amoxicillin, Ampicillin, Tetracycline, Vancomycin, Cefoxitin 12. Known hypersensitivity to >4 first-line antimicrobial therapies against Bifidobacterium infantis Bi-26TM: Gentamicin, Kanamycin, Streptomycin, Tetracycline, Erythromycin, Clindamycin, Ampicillin, Vancomycin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Phase 1 - Standard Dose; 1 capsule	Dietary supplement: Three-Strain Probiotic; ≥ 500 million AFU of Clostridium butyricum strain WB-STR-0006, Akkermansia muciniphila strain WB-STR-0001, Bifidobacterium infantis Bi-26TM, 174 mg chicory inulin (prebiotic), 19mg Microcrystalline Cellulose MCC, 4mg L-Leucine, and 3mg Silica (excipients) to be taken once daily with food
Active Comparator: Phase 1 - High Dose; 2 capsules	Dietary supplement: Three-Strain Probiotic; ≥ 500 million AFU of Clostridium butyricum strain WB-STR-0006, Akkermansia muciniphila strain WB-STR-0001, Bifidobacterium infantis Bi-26TM, 174 mg chicory inulin (prebiotic), 19mg Microcrystalline Cellulose MCC, 4mg L-Leucine, and 3mg Silica (excipients) to be taken once daily with food
Active Comparator: Phase 2 - Active; Dose selected from Phase 1	Dietary supplement: Three-Strain Probiotic; ≥ 500 million AFU of Clostridium butyricum strain WB-STR-0006, Akkermansia muciniphila strain WB-STR-0001, Bifidobacterium infantis Bi-26TM, 174 mg chicory inulin (prebiotic), 19mg Microcrystalline Cellulose MCC, 4mg L-Leucine, and 3mg Silica (excipients) to be taken once daily with food
Placebo Comparator: Phase 2 - Placebo	Dietary supplement: Phase 2 - Placebo; Phase 2 - Matching Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1 - Safety and Tolerability - As assessed by Occurrence of Adverse of Events	Phase I: To evaluate the safety and tolerability of 8-week daily supplementation of high-dose versus standard dose Three-Strain Probiotic as assessed by Occurrence of any Adverse Events Change from baseline to week 8.	8 weeks
Phase 2 - Safety and Tolerability - As assessed by Occurrence of Adverse of Events	Phase 2: To evaluate the safety and tolerability of 8-week daily supplementation of the selected dose (from Phase I) Three-Strain Probiotic as assessed by Occurrence of any Adverse Events Change from baseline to week 8	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1 - Safety - Blood Biomarkers - Red Blood Cell Count	(10e12/L)	8 weeks
Phase 1 - Safety - Blood Biomarkers - White Blood Cell Count	(10e9/L)	8 weeks
Phase 1 - Safety - Blood Biomarkers - Hemoglobin	(g/L)	8 weeks
Phase 1 - Safety - Blood Biomarkers - Alanine Aminotransferase	(IU/L)	8 weeks
Phase 1 - Safety - Blood Biomarkers - Aspartate Aminotransferase	(IU/L)	8 weeks
Phase 1 - Safety - Blood Biomarkers - Serum Creatinine	(umol/L)	8 weeks
Phase 1 - Safety - Blood Biomarkers - eGFR	(mL/min/1.73 m²)	8 weeks
Phase 1 - Safety - Blood Biomarkers - Sodium	(mmol/L)	8 weeks
Phase 1 - Safety - Blood Biomarkers - Potassium	(mmol/L)	8 weeks
Phase 1 - Safety - Blood Biomarkers - Total Cholesterol	(mmol/L)	8 weeks
Phase 1 - Safety - Blood Biomarkers - LDL Cholesterol	(mmol/L)	8 weeks
Phase 1 - Safety - Blood Biomarkers - HDL Cholesterol	(mmol/L)	8 weeks
Phase 1 - Safety - Blood Biomarkers - LDL:HDL Cholesterol Ratio	(no units)	8 weeks
Phase 1 - Safety - Blood Biomarkers - Fasting Glucose	(mmol/L)	8 weeks
Phase 1 - Vital signs - Systolic Blood Pressure	mmHG	8 weeks
Phase 1 - Vital signs - Diastolic Blood Pressure	mmHG	8 weeks
Phase 1 - Vital signs - Heart Rate	bpm	8 weeks
Phase 1 - Vital signs - Temperature	˚C	8 weeks
Phase 1 - Total Food Cravings - Food Cravings Inventory (FCI-UK)	The Food Craving Inventory (FCI-UK) is a UK-specific version of the Food Craving Inventory designed to measure the frequency of cravings for specific foods over the past month. The questionnaire lists 27 food items and generates total food cravings scores.	8 weeks
Phase 1 - Food Cravings - Food Cravings Questionnaire-Trait-reduced (FCQ-T-r)	The Food Cravings Questionnaire- Trait- reduced (FCQ-T-r) is a 15-item reduced version of the Food Cravings Questionnaire (FCQ). Items included in the FCQ-T-r from the original version subscales include lack of control overeating (5 items), thoughts or preoccupation with food (5 items), intentions and plans to consume food (2 items), emotions before or during food craving (2 items), and cues that may trigger food craving (1 item). Participants indicate on a 6-point scale from 'never/not applicable to always' how frequently each of the 15 statements relating to food cravings is true for them.	8 weeks
Phase 1 - Meal Tolerance Test - Plasma GLP-1 (Total)	Meal Tolerance Test - initiated in the fasting state with samples collected at T0 (fasting), T30, T60, T90, T120 & T180 mins following a standardised meal. Measured in pg/ml.	8 weeks
Phase 1 - Meal Tolerance Test - Plasma Glucose	Meal Tolerance Test - initiated in the fasting state with samples collected at T0 (fasting), T30, T60, T90, T120 & T180 mins following a standardised meal. Measured in mmol/L.	8 weeks
Phase 1 - Meal Tolerance Test - Satiety (VAS)	Meal Tolerance Test - initiated in the fasting state with samples collected at T0 (fasting), T30, T60, T90, T120 & T180 mins following a standardised meal. VAS scales follow 0-100 measurement.	8 weeks
Phase 1 - Meal Tolerance Test - Hunger (VAS)	Meal Tolerance Test - initiated in the fasting state with samples collected at T0 (fasting), T30, T60, T90, T120 & T180 mins following a standardised meal. VAS scales follow 0-100 measurement.	8 weeks
Phase 1 - Meal Tolerance Test - Fullness (VAS)	Meal Tolerance Test - initiated in the fasting state with samples collected at T0 (fasting), T30, T60, T90, T120 & T180 mins following a standardised meal. VAS scales follow 0-100 measurement.	8 weeks
Phase 1 - Meal Tolerance Test - Desire to eat (VAS)	Meal Tolerance Test - initiated in the fasting state with samples collected at T0 (fasting), T30, T60, T90, T120 & T180 mins following a standardised meal. VAS scales follow 0-100 measurement.	8 weeks
Phase 1 - Weight	kg	8 weeks
Phase 1 - BMI	kg/m2	8 weeks
Phase 2 - Vital signs - Systolic Blood Pressure	mmHG	8 weeks
Phase 2 - Vital signs - Diastolic Blood Pressure	mmHG	8 weeks
Phase 2 - Vital signs - Heart Rate	bpm	8 weeks
Phase 2 - Vital signs - Temperature	˚C	8 weeks
Phase 2 - Total Food Cravings - Food Cravings Inventory (FCI-UK)	The Food Craving Inventory (FCI-UK) is a UK-specific version of the Food Craving Inventory designed to measure the frequency of cravings for specific foods over the past month. The questionnaire lists 27 food items and generates total food cravings scores.	8 weeks
Phase 2 - Food Cravings - Food Cravings Questionnaire-Trait-reduced (FCQ-T-r)	The Food Cravings Questionnaire- Trait- reduced (FCQ-T-r) is a 15-item reduced version of the Food Cravings Questionnaire (FCQ). Items included in the FCQ-T-r from the original version subscales include lack of control overeating (5 items), thoughts or preoccupation with food (5 items), intentions and plans to consume food (2 items), emotions before or during food craving (2 items), and cues that may trigger food craving (1 item). Participants indicate on a 6-point scale from 'never/not applicable to always' how frequently each of the 15 statements relating to food cravings is true for them.	8 weeks
Phase 2 - Meal Tolerance Test - Plasma GLP-1 (Total)	Meal Tolerance Test - initiated in the fasting state with samples collected at T0 (fasting), T30, T60, T90, T120 & T180 mins following a standardised meal. Measured in pg/ml.	8 weeks
Phase 2 - Meal Tolerance Test - Plasma Glucose	Meal Tolerance Test - initiated in the fasting state with samples collected at T0 (fasting), T30, T60, T90, T120 & T180 mins following a standardised meal. Measured in mmol/L	8 weeks
Phase 2 - Meal Tolerance Test - Plasma GLP-2	Meal Tolerance Test - initiated in the fasting state with samples collected at T0 (fasting), T30, T60, T90, T120 & T180 mins following a standardised meal. Measured in pg/ml.	8 weeks
Phase 2 - Meal Tolerance Test - Peptide YY	Meal Tolerance Test - initiated in the fasting state with samples collected at T0 (fasting), T30, T60, T90, T120 & T180 mins following a standardised meal. Measured in pg/ml.	8 weeks
Phase 2 - Meal Tolerance Test - Plasma Insulin	Meal Tolerance Test - initiated in the fasting state with samples collected at T0 (fasting), T30, T60, T90, T120 & T180 mins following a standardised meal. Measured in pg/ml.	8 weeks
Phase 2 - Meal Tolerance Test - Satiety (VAS)	Meal Tolerance Test - initiated in the fasting state with samples collected at T0 (fasting), T30, T60, T90, T120 & T180 mins following a standardised meal. VAS scales follow 0-100 measurement.	8 weeks
Phase 2 - Meal Tolerance Test - Hunger (VAS)	Meal Tolerance Test - initiated in the fasting state with samples collected at T0 (fasting), T30, T60, T90, T120 & T180 mins following a standardised meal. VAS scales follow 0-100 measurement.	8 weeks
Phase 2 - Meal Tolerance Test - Fullness (VAS)	Meal Tolerance Test - initiated in the fasting state with samples collected at T0 (fasting), T30, T60, T90, T120 & T180 mins following a standardised meal. VAS scales follow 0-100 measurement.	8 weeks
Phase 2 - Meal Tolerance Test - Desire to eat (VAS)	Meal Tolerance Test - initiated in the fasting state with samples collected at T0 (fasting), T30, T60, T90, T120 & T180 mins following a standardised meal. VAS scales follow 0-100 measurement.	8 weeks
Phase 2 - Weight	kg	8 weeks
Phase 2 - BMI	kg/m2	8 weeks
Phase 2 - Hormonal Health - Leptin	pg/ml	8 weeks
Phase 2 - Hormonal Health - Ghrelin	pg/ml	8 weeks
Phase 2 - Inflammation - IL-6	pg/ml	8 weeks
Phase 2 - Inflammation - IL-17	pg/ml	8 weeks
Phase 2 - Safety - Blood Biomarkers - Red Blood Cell Count	(10e12/L)	8 weeks
Phase 2 - Safety - Blood Biomarkers - White Blood Cell Count	(10e9/L)	8 weeks
Phase 2 - Safety - Blood Biomarkers - Hemoglobin	(g/L)	8 weeks
Phase 2 - Safety - Blood Biomarkers - Alanine Aminotransferase	(IU/L)	8 weeks
Phase 2 - Safety - Blood Biomarkers - Aspartate Aminotransferase	(IU/L)	8 weeks
Phase 2 - Safety - Blood Biomarkers - Serum Creatinine	(umol/L)	8 weeks
Phase 2 - Safety - Blood Biomarkers - eGFR	(mL/min/1.73 m²)	8 weeks
Phase 2 - Safety - Blood Biomarkers - Sodium	(mmol/L)	8 weeks
Phase 2 - Safety - Blood Biomarkers - Potassium	(mmol/L)	8 weeks
Phase 2 - Safety - Blood Biomarkers - Total Cholesterol	(mmol/L)	8 weeks
Phase 2 - Safety - Blood Biomarkers - LDL Cholesterol	(mmol/L)	8 weeks
Phase 2 - Safety - Blood Biomarkers - HDL Cholesterol	(mmol/L)	8 weeks
Phase 2 - Safety - Blood Biomarkers - LDL:HDL Cholesterol Ratio	(no units)	8 weeks
Phase 2 - Safety - Blood Biomarkers - Fasting Glucose	(mmol/L)	8 weeks

Collaborators and Investigators

• Sponsor: Pendulum Therapeutics
• Collaborators: Atlantia Food Clinical Trials; APC Microbiome Ireland
• Investigators: Principal Investigator: Noel Caplice, MD, APC Microbiome Ireland; Study Director: Adam Perlman, MD, MPH, Pendulum Therapeutics, Inc

Publications and helpful links

General Publications

• Belzer C, de Vos WM. Microbes inside--from diversity to function: the case of Akkermansia. ISME J. 2012 Aug;6(8):1449-58. doi: 10.1038/ismej.2012.6. Epub 2012 Mar 22.
• Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev. 2007 Oct;87(4):1409-39. doi: 10.1152/physrev.00034.2006.
• Perraudeau F, McMurdie P, Bullard J, Cheng A, Cutcliffe C, Deo A, Eid J, Gines J, Iyer M, Justice N, Loo WT, Nemchek M, Schicklberger M, Souza M, Stoneburner B, Tyagi S, Kolterman O. Improvements to postprandial glucose control in subjects with type 2 diabetes: a multicenter, double blind, randomized placebo-controlled trial of a novel probiotic formulation. BMJ Open Diabetes Res Care. 2020 Jul;8(1):e001319. doi: 10.1136/bmjdrc-2020-001319.
• Huber H, Schieren A, Holst JJ, Simon MC. Dietary impact on fasting and stimulated GLP-1 secretion in different metabolic conditions - a narrative review. Am J Clin Nutr. 2024 Mar;119(3):599-627. doi: 10.1016/j.ajcnut.2024.01.007. Epub 2024 Jan 11.
• Yoon HS, Cho CH, Yun MS, Jang SJ, You HJ, Kim JH, Han D, Cha KH, Moon SH, Lee K, Kim YJ, Lee SJ, Nam TW, Ko G. Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice. Nat Microbiol. 2021 May;6(5):563-573. doi: 10.1038/s41564-021-00880-5. Epub 2021 Apr 5.

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2024
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: April 1, 2026
• First Submitted That Met QC Criteria: April 28, 2026
• First Posted (Actual): May 5, 2026

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Insulin; GLP-1; Probiotics; Food Cravings; Akkermansia Muciniphila
• Additional Relevant MeSH Terms: Metabolic Diseases; Glucose Metabolism Disorders; Hyperinsulinism; Nutritional and Metabolic Diseases; Insulin Resistance
• Other Study ID Numbers: PDL-25-01P - AFCRO-181

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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