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

N/AActive Not RecruitingNCT07566884

Pendulum Therapeutics30 enrolled

Overview

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.

A Two-Phase Study safety and tolerance study: Phase I: Open-Label Study Phase II: Randomised Double-Blind, Placebo-Controlled Study

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Healthy Adults

Interventions

Three-Strain ProbioticDIETARY_SUPPLEMENT

≥ 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

Phase 2 - PlaceboDIETARY_SUPPLEMENT

Phase 2 - Matching Placebo

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

Atlantia Clinical Trials

Cork, Ireland

Outcomes

Primary Outcomes

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.

Time frame: 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

Time frame: 8 weeks

Secondary Outcomes

Phase 1 - Safety - Blood Biomarkers - Red Blood Cell Count

(10e12/L)

Time frame: 8 weeks

Phase 1 - Safety - Blood Biomarkers - White Blood Cell Count

(10e9/L)

Time frame: 8 weeks

Phase 1 - Safety - Blood Biomarkers - Hemoglobin

(g/L)

Time frame: 8 weeks

Phase 1 - Safety - Blood Biomarkers - Alanine Aminotransferase

(IU/L)

Time frame: 8 weeks

Phase 1 - Safety - Blood Biomarkers - Aspartate Aminotransferase

(IU/L)

Time frame: 8 weeks

Phase 1 - Safety - Blood Biomarkers - Serum Creatinine

(umol/L)

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Phase 1 - Safety - Blood Biomarkers - eGFR

(mL/min/1.73 m²)

Time frame: 8 weeks

Phase 1 - Safety - Blood Biomarkers - Sodium

(mmol/L)

Time frame: 8 weeks

Phase 1 - Safety - Blood Biomarkers - Potassium

(mmol/L)

Time frame: 8 weeks

Phase 1 - Safety - Blood Biomarkers - Total Cholesterol

(mmol/L)

Time frame: 8 weeks

Phase 1 - Safety - Blood Biomarkers - LDL Cholesterol

(mmol/L)

Time frame: 8 weeks

Phase 1 - Safety - Blood Biomarkers - HDL Cholesterol

(mmol/L)

Time frame: 8 weeks

Phase 1 - Safety - Blood Biomarkers - LDL:HDL Cholesterol Ratio

(no units)

Time frame: 8 weeks

Phase 1 - Safety - Blood Biomarkers - Fasting Glucose

(mmol/L)

Time frame: 8 weeks

Phase 1 - Vital signs - Systolic Blood Pressure

mmHG

Time frame: 8 weeks

Phase 1 - Vital signs - Diastolic Blood Pressure

mmHG

Time frame: 8 weeks

Phase 1 - Vital signs - Heart Rate

bpm

Time frame: 8 weeks

Phase 1 - Vital signs - Temperature

˚C

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 8 weeks

Phase 1 - Weight

Time frame: 8 weeks

Phase 1 - BMI

kg/m2

Time frame: 8 weeks

Phase 2 - Vital signs - Systolic Blood Pressure

mmHG

Time frame: 8 weeks

Phase 2 - Vital signs - Diastolic Blood Pressure

mmHG

Time frame: 8 weeks

Phase 2 - Vital signs - Heart Rate

bpm

Time frame: 8 weeks

Phase 2 - Vital signs - Temperature

˚C

Time frame: 8 weeks

Phase 2 - Total Food Cravings - Food Cravings Inventory (FCI-UK)

Time frame: 8 weeks

Phase 2 - Food Cravings - Food Cravings Questionnaire-Trait-reduced (FCQ-T-r)

Time frame: 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.

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 8 weeks

Phase 2 - Weight

Time frame: 8 weeks

Phase 2 - BMI

kg/m2

Time frame: 8 weeks

Phase 2 - Hormonal Health - Leptin

pg/ml

Time frame: 8 weeks

Phase 2 - Hormonal Health - Ghrelin

pg/ml

Time frame: 8 weeks

Phase 2 - Inflammation - IL-6

pg/ml

Time frame: 8 weeks

Phase 2 - Inflammation - IL-17

pg/ml

Time frame: 8 weeks

Phase 2 - Safety - Blood Biomarkers - Red Blood Cell Count

(10e12/L)

Time frame: 8 weeks

Phase 2 - Safety - Blood Biomarkers - White Blood Cell Count

(10e9/L)

Time frame: 8 weeks

Phase 2 - Safety - Blood Biomarkers - Hemoglobin

(g/L)

Time frame: 8 weeks

Phase 2 - Safety - Blood Biomarkers - Alanine Aminotransferase

(IU/L)

Time frame: 8 weeks

Phase 2 - Safety - Blood Biomarkers - Aspartate Aminotransferase

(IU/L)

Time frame: 8 weeks

Phase 2 - Safety - Blood Biomarkers - Serum Creatinine

(umol/L)

Time frame: 8 weeks

Phase 2 - Safety - Blood Biomarkers - eGFR

(mL/min/1.73 m²)

Time frame: 8 weeks

Phase 2 - Safety - Blood Biomarkers - Sodium

(mmol/L)

Time frame: 8 weeks

Phase 2 - Safety - Blood Biomarkers - Potassium

(mmol/L)

Time frame: 8 weeks

Phase 2 - Safety - Blood Biomarkers - Total Cholesterol

(mmol/L)

Time frame: 8 weeks

Phase 2 - Safety - Blood Biomarkers - LDL Cholesterol

(mmol/L)

Time frame: 8 weeks

Phase 2 - Safety - Blood Biomarkers - HDL Cholesterol

(mmol/L)

Time frame: 8 weeks

Phase 2 - Safety - Blood Biomarkers - LDL:HDL Cholesterol Ratio

(no units)

Time frame: 8 weeks

Phase 2 - Safety - Blood Biomarkers - Fasting Glucose

(mmol/L)

Time frame: 8 weeks