Safety and efficacy of a potential new probiotic in healthy volunteers Other
Conditions
Interventions
This is a phase 0/1 clinical trial, investigating the safety of a 4-week oral supplementation of a new Akkermansia strain in three different doses 1 x 10^9, 1 x 10^10 and 2 x 10^10 colony forming uni
Sponsors
Danisco Sweeteners Oy
Eligibility
Sex/Gender
All
Age
25 Years to 65 Years
Inclusion criteria
Inclusion criteria: 1. Provision of signed and dated informed consent form 2. Stated willingness to comply with all trial procedures and availability for the duration of the trial 3. Free-living females and males of age 25 to 65 years (limits included) 4. Low risk of metabolic syndrome based on the following parameters: 4.1. HbA1C 4.0 -– 5.6 % (20-42 mmol/ml) 4.2. LDL 1.0 in males and > 1.2 in females mmol/l (> 38.7 in males and > 46.4-mg/dl in females) 4.5. BMI 18.5 – 24.9 kg/m2 4.6. Waist circumference: males < 94 cm, females < 80 cm 4.7. Waist-hip-ratio: males < 0.95, females < 0.8 5. An individual who agrees to maintain their usual lifestyle throughout the trial, i.e., agrees not to change their dietary habits and level of exercise etc. during the trial 6. Females of child-bearing potential must agree to use medically approved methods for birth control including condoms with or without spermicides, hormonal contraceptives (estrogen and/or progestin products; either oral, intrauterine, or epidermal) or intrauterine device with copper. The contraceptive method should have been in place for at least 3 cycles before the beginning of the trial and should not be modified during the trial 7. Postmenopausal women aged 45 years and above who have not had a period for at least 12 months and are not using hormonal contraception. If on hormone replacement therapy, they must have been applying the estrogenic or estrogenic/progestin treatment for at least 3 months before the beginning of the trial. 8. Ability of the participant, in the investigator’s opinion, to comprehend the full nature and purpose of the trial including possible risks and side effects
Exclusion criteria
Exclusion criteria: 1. Having hypersensitivity or history of allergy to the trial product components, or a history of adverse effects, intolerance, or allergic reactions attributed to any medications 2. Suffering from a chronic disease (e.g., autoimmune disease, cancer, renal failure, HIV, immunodeficiency, hepatic or biliary disorders, arthritis, uncontrolled cardiac disease, terminal illness) or from an illness that may preclude the participant’s ability to complete the trial or that may confound the trial outcomes according to the assessment by the investigator 3. History of heart failure with reduced left ventricular ejection fraction (LVEF) defined as any past measurement of LVEF = 40% 4. Unstable heart failure with preserved ejection fraction, defined as: a) New York Heart Association (NYHA) class III-IV or, b) Hospitalisation or emergency room visit for heart failure during the past one year or, c) Need for intravenous diuretics in the outpatient setting within 6 months of Screening or, d) Concomitant treatment with a high dose of diuretics (i.e., furosemide 80 mg/day or equivalent) 5. Abnormal laboratory values at screening, including any of the following: 5.1. AST or ALT = 5 × ULN (upper limit of normal) 5.2. Alkaline phosphatase > 2 × ULN 5.3. Impaired renal function defined as eGFR = 60 mL/minute/1.73 m2 at screening (estimated according to the CKD Epidemiology collaboration) (Inker et al 2021) 5.4. Albumin 160 mm Hg or mean diastolic blood pressure >100 mm Hg (based on the average of 3 blood pressure readings if the first reading is outside of these limits). 7. History of diagnosed gastrointestinal complications at screening or randomization. (e.g., Crohn’s disease, ulcer, IBS-mixed, IBS-constipation, IBS-diarrhea, celiac disease) 8. Prior abdominal surgery (e.g., gastric bypass, gastrectomy, gastric band, visceral surgery) at screening or randomization that, in the opinion of the investigator, may present a risk for the participant or confound trial results. 9. Clinically significant diagnosis of any eating disorder at screening or randomisation (e.g., anorexia, bulimia) that may impact the safety of the subject or the trial data as per investigator judgement. 10. Antibiotic course within 3 months before screening or any active infection during the screening period or ongoing chronic infection for the duration of the study. 11. Having a lifestyle deemed incompatible with the trial according to the investigator, e.g., a specific extreme diet (e.g., hypocaloric, ketogenic), intense physical activity > 10 hours/week. 12. Any self-declared clinically significant alcohol misuse (more than 14 units of alcohol per week) at screening or randomisation that may impact the safety of the subject or the trial data. 13. Self-declared use of illicit drugs at screening or randomisation that may impact the safety of the subject or the trial data as per investigator judgement. 14. Pregnant or lactating female, or pregnancy planned during the trial 15. The investigator believes that the individual may be uncooperative and/or noncompliant and should therefore not participate in the trial 16. Presenting a psychological or linguistic incapacity to understand and sign the inform
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety is measured by monitoring adverse events daily, gastrointestinal symptoms via the Gastrointestinal Symptom Rating Scale (GSRS) once per week, and stool frequency and consistency using a bowel frequency questionnaire and the Bristol Stool Scale Assessment daily. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Changes in safety biomarkers are measured using the following laboratory analyses at days 0, 14, 28 and 56: 1.1. Blood safety analyses: hemoglobin, hematocrit, red blood cells, white blood cells, platelets, urea, creatinine, bilirubin, minerals: calcium, phosphate, potassium, sodium, chloride, magnesium, and bicarbonate. 1.2. Urine safety analyses: aspect and color as per local lab, density, bilirubin levels, protein (albumin), glucose, ketones, nitrites, pH, and presence of red and white cells. 1.3. Liver function: alanine transaminase (ALT), gamma-glutamyltranspetidase (GGT), alkaline phosphatase (AP), aspartate aminotransferase (AST), 1.4. Tissue damage-related markers: Lactase dehydrogenase (s-LD), creatine kinase (p-CK) 1.5. High-sensitivity C-reactive protein (hs-CRP) | — |
Countries
England, United Kingdom
Contacts
Public ContactKasia Wzietal
Outcome results
None listed