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| Name | Class |
|---|---|
| Atlantia Food Clinical Trials | INDUSTRY |
| APC Microbiome Ireland | UNKNOWN |
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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Phase 1 - Standard Dose | Active Comparator | 1 capsule |
|
| Phase 1 - High Dose | Active Comparator | 2 capsules |
|
| Phase 2 - Active | Active Comparator | Dose selected from Phase 1 |
|
| Phase 2 - Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Three-Strain Probiotic | Dietary 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 |
| 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 |
| 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) |
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Inclusion Criteria:
To be eligible for inclusion, the Participant must fulfill all the following criteria:
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:
Participants who are pregnant or wish to become pregnant during the study or who are lactating and/or currently breastfeeding.
Participants currently of biological childbearing potential, but not using a continuous effective method of contraception, as outlined below:
Has food allergies or other issues with foods that would preclude intake of the Study Products.
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:
Probiotics/Prebiotics
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
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| Name | Affiliation | Role |
|---|---|---|
| Adam Perlman, MD, MPH | Pendulum Therapeutics, Inc | Study Director |
| Noel Caplice, MD | APC Microbiome Ireland | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Atlantia Clinical Trials | Cork | Ireland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 17928588 | Background | Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev. 2007 Oct;87(4):1409-39. doi: 10.1152/physrev.00034.2006. | |
| 22437156 | Background | 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. |
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| ID | Term |
|---|---|
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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|
| Phase 2 - Placebo | Dietary Supplement | Phase 2 - Matching Placebo |
|
| 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 |
| 38218319 | Background | 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. |
| 33820962 | Background | 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. |
| 32675291 | Background | 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. |