Clinical trial NCT02198703: A Trial to Evaluate the Efficacy of AB-Life Probiotic Product on LDL-Cholesterol Reduction in Moderate Hypercholesterolemia
Official title: RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED CLINICAL TRIAL FOR EVALUATING THE EFFICACY OF AB-LIFE PROBIOTIC PRODUCT ON THE LDL-CHOLESTEROL REDUCTION IN THE MODERATE HYPERCHOLESTEROLEMIA
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Moderate Hypercholesterolemia
Keywords: Probiotics
AB-Life
LDL-cholesterol
Hypercholesterolemia
Lead sponsor: AB Biotics, SA
Sponsor class: INDUSTRY
First posted: 2014-07-24
Enrollment: 104
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study aims to demonstrate the effect of the chronic consumption of AB-Life probiotic blend on blood LDL cholesterol level in volunteers with moderate hypercholesterolemia.


Eligibility criteria: Inclusion Criteria:

To be eligible to the study, male and female volunteers will have to fulfill the following criteria (assessment based on the medical examination performed at V1 with a checking at V3):

* Age between 18 and 65 years (limits included).
* BMI between 18,5 and 30 kg/m² ((limits excluded).
* For women : Non menopausal with reliable contraception since at least two cycles before the beginning of the study and agreeing to keep it during the entire duration of the study (condom alone without spermicide gel and oestrogenic contraceptive excluded) or menopausal without oestrogenic replacement therapy.
* Good general and mental health with in the opinion of the investigator: no clinically significant and relevant abnormalities of medical history or physical examination.
* Able and willing to participate to the study by complying with the protocol procedures as evidenced by his dated and signed informed consent form.
* Affiliated with a social security scheme.
* Agree to be registered on the volunteers in biomedical research file.

After V1 biological analysis the subjects will be eligible to the visit V2 on the following criteria:

- Fasting plasma LDLc level (Friedewald estimation method) between 1,3 and 1,89 g/L (3,35 - 4,92 mmol/L, limits included with ± 2% tolerated around).

After V2 biological analysis the subjects will be eligible to the study on the following criteria:

- Fasting plasma LDLc level (Friedewald estimation method) between 1,3 and 1,89 g/L (3,35 - 4,92 mmol/L, limits included with ± 2% tolerated around).

A re-screening can occur from 2 months after the exit of study for failure to comply with the one or more of the eligibility criteria listed above.

Exclusion Criteria:

Volunteers with the following criteria will be considered as non eligible to the study (assessment based on the medical examination performed at V1 with a checking at V3):

* Suffering from a metabolic disorder such as diabetes, uncontrolled thyroidal trouble or other chronic severe disease.
* Suffering from a severe chronic disease (e.g. cancer, HIV, renal failure, hepatic or biliary disorders ongoing, chronic inflammatory digestive disease, arthritis or other chronic respiratory trouble, etc.) or gastrointestinal disorders found to be inconsistent with the conduct of the study by the investigator (e.g. celiac disease).
* With a history of ischemic cardiovascular event or, during the previous 6 months a surgical procedure.
* With a known or suspected food allergy or intolerance or hypersensitivity to any of the study products' ingredient.
* Suffering from an uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg and diastolic blood pressure ≥ 100 mmHg).
* Pregnant or lactating women or intending to become pregnant within 5 months ahead.
* Under lipid-lowering treatment (e.g. statins, fibrates, ezetimibe, bile acid sequestrants, niacin, etc.) or stopped less than 4 months before the randomization.
* Under medication which could affect blood lipid parameters (e.g. long-term corticosteroid systemic drug, systemic antibodies, androgens or phenytoin, etc.) or stopped less than 1 month before the randomization (stable long-term treatment with beta blocker or thiazide diuretics tolerated).
* Regular intake of dietary supplements or "functional foods" which may interfere with lipid absorption and/or metabolism (e.g. rich in plant stanol or sterol like PRO-ACTIV or DANACOL products, red yeast rice, policosanol, omega-3 fatty acids like fish oils, ST HUBERT OMEGA 3 or PRIMEVERE products, soya protein, oat fiber like QUAKER OATS, psyllium, chitosan, guar gum, inulin, etc.) or stopped less than 3 months before the randomization.
* Under treatment which could disturb microbiota balance or stopped in a too short period before the randomization (e.g. less than one month for laxatives, less than 6 weeks for antibiotics).
* Regular intake of dietary supplements or "functional foods" containing prebiotics, probiotics or symbiotics (e.g. BION 3, LACTIBIANE, ACTIMEL, ACTIVIA, etc.) or stopped less than 1 month before the randomization.
* Under treatment or dietary supplement which could significantly affect parameter(s) followed during the study according to the investigator or stopped in a too short period before the randomization.
* With significant change in food habits or in physical activity in the 3 months before randomization or not agreeing to keep them unchanged throughout the study.
* With reported body weight variation \> 5% in the 3 months prior the randomization or with a hyper or hypocaloric diet planned in the next 5 months.
* With a personal history of anorexia nervosa, bulimia or significant eating disorders according to the investigator.
* Consuming more than 3 standard drinks of alcoholic beverage daily for men or 2 standard drinks daily for women or not agreeing to keep his alcohol consumption habits unchanged throughout the study.
* Smoking more than 10 cigarettes daily or not agreeing to keep his smoking habits unchanged throughout the study.
* Recent history of chronic alcohol or drug abuse (in the last 2 years).
* Having a lifestyle deemed incompatible with the study according to the investigator including high level physical activity (defined as more than 10 hours of significant physical activity a week, walking excluded).
* Who made a blood donation in the 3 months before the randomization or intending to make it within 4 months ahead.
* Taking part in another clinical trial or being in the exclusion period of a previous clinical trial.
* Having received, during the last 12 months, indemnities for clinical trial higher or equal to 4500 Euros.
* Under legal protection (guardianship, wardship) or deprived from his rights following administrative or judicial decision.
* Presenting a psychological or linguistic incapability to sign the informed consent.
* Impossible to contact in case of emergency.

After V1 biological analysis the subjects will be considered as non eligible to the study on the following criteria :

* Fasting plasma glucose level \> 1,26 g/L (6,99 mmol/L).
* Fasting plasma triglycerides \> 3,5 g/L (3,95 mmol/L).
* Fasting plasma TC, HDLc or insulin with an abnormality judged as clinically significant according to the investigator.

After V2 biological analysis the subjects will be considered as non eligible to the study on the following criteria:

* Fasting plasma TC, HDL or TG with an abnormality judged as clinically significant according to the investigator.
* Serum AST, ALT, GGT, ALP or bilirubin with an abnormality judged as clinically significant according to the investigator.
* Serum urea or creatinine with an abnormality judged as clinically significant according to the investigator.
* Complete blood count with clinically significant abnormality according to the investigator.

Volunteers with the following criteria at the V3 will be considered as non eligible to the study:

* Capsules' consumption less than 80% of capsules during the run-in period (since V1) according to the quantities returned.
* Gastroenteritis history finished less than 2 weeks before the randomization.

The included subjects who cannot be randomized at V3 because of a too short wash out period related to the non inclusion criteria E8, E10, E12 or E34 can delay their visit V3 without to exceed 28 days from the visit V2.

A re-screening can occur from 2 months after the exit of study for failure to comply with the one or more of the eligibility criteria listed above (except for E33 criteria).

Primary outcomes:
measure: Change of the fasting blood LDL cholesterol concentration
timeFrame: 12 weeks
Secondary outcomes:
measure: Change in fasting blood total cholesterol concentration
timeFrame: 4 weeks
measure: Change in fasting blood total cholesterol concentration
timeFrame: 12 weeks
measure: Change in fasting blood LDLc concentration
timeFrame: 4 weeks
measure: Change in fasting blood HDLc concentration
timeFrame: 4 weeks
measure: Change in fasting blood HDLc concentration
timeFrame: 12 weeks
measure: Change in fasting blood ratio total cholesterol / HDLc concentrations
timeFrame: 4 weeks
measure: Change in fasting blood ratio total cholesterol / HDLc concentrations
timeFrame: 12 weeks
measure: Change in fasting blood ratio LDLc / HDLc concentrations
timeFrame: 4 weeks
measure: Change in fasting blood ratio LDLc / HDLc concentrations
timeFrame: 12 weeks
measure: Change in fasting blood triglycerides concentration
timeFrame: 4 weeks
measure: Change in fasting blood triglycerides concentration
timeFrame: 12 weeks
measure: Change in fasting blood Apo A1 concentration
timeFrame: 4 weeks
measure: Change in fasting blood Apo A1 concentration
timeFrame: 12 weeks
measure: Change in fasting blood Apo B100 concentration
timeFrame: 4 weeks
measure: Change in fasting blood Apo B100 concentration
timeFrame: 12 weeks
measure: Change in fasting blood insulin concentration
timeFrame: 4 weeks
measure: Change in fasting blood insulin concentration
timeFrame: 12 weeks
measure: Change in fasting blood glucose concentration
timeFrame: 12 weeks
measure: Change in fasting blood glucose concentration
timeFrame: 4 weeks
measure: Change in fasting blood acetate concentration
timeFrame: 12 weeks
measure: Change in fasting blood propionate concentration
timeFrame: 12 weeks
measure: Change in fasting blood acetate / propionate concentrations
timeFrame: 12 weeks
measure: Change in SCORE - European Low Risk Chart of fatal cardiovascular disease
timeFrame: 4 weeks
measure: Change in SCORE - European Low Risk Chart of fatal cardiovascular disease
timeFrame: 12 weeks
measure: Change in fasting blood hsCRP concentration
timeFrame: 12 weeks
measure: Complete blood count
timeFrame: 12 weeks
measure: Blood Alkaline Phosphatase
timeFrame: 12 weeks
measure: Blood Alanine Amino Transferase
timeFrame: 12 weeks
measure: Blood Aspartate Amino Transferase
timeFrame: 12 weeks
measure: Blood Gamma Glutamyl Transpeptidase
timeFrame: 12 weeks
measure: Blood total bilirubin
timeFrame: 12 weeks
measure: Blood urea
timeFrame: 12 weeks
measure: Blood creatinine
timeFrame: 12 weeks
measure: Heart rate
timeFrame: 4 weeks
measure: Heart rate
timeFrame: 12 weeks
measure: Systolic Blood Pressure
timeFrame: 4 weeks
measure: Diastolic Blood Pressure
timeFrame: 4 weeks
measure: Diastolic Blood Pressure
timeFrame: 12 weeks
measure: Systolic Blood Pressure
timeFrame: 12 weeks
measure: Body weight
timeFrame: 4 weeks
measure: Body weight
timeFrame: 12 weeks
measure: Physical Activity Score
timeFrame: 12 weeks
measure: Total energy intake
timeFrame: 12 weeks
measure: Percentage of energy intake from fat
timeFrame: 12 weeks
measure: Dietary fiber intake
timeFrame: 12 weeks
measure: Saturated Fatty Acids intake
timeFrame: 12 weeks
Other outcomes:
measure: Fasting blood PCSK9 concentration
timeFrame: 12 weeks
measure: Fasting blood FGF-19 concentration
timeFrame: 12 weeks
measure: Fasting blood LDLox concentration
timeFrame: 12 weeks
measure: Fasting blood fibrinogen concentration
timeFrame: 12 weeks
measure: Fasting blood biliary acids concentrations
timeFrame: 12 weeks
measure: Fecal concentrations of neutral sterol including cholesterol and its secondary metabolites
timeFrame: 12 weeks
measure: Fecal concentrations of phytosterols
timeFrame: 12 weeks
measure: Fecal concentrations of volatil fatty acids
timeFrame: 12 weeks
measure: Fecal concentrations of branched chain fatty acids
timeFrame: 12 weeks
measure: Fecal concentrations of biliary acids
timeFrame: 12 weeks
measure: Fecal concentrations of AB-Life probiotic strains
timeFrame: 12 weeks
measure: Fecal concentration of calprotectin
timeFrame: 12 weeks
measure: Fasting blood sodium concentration
timeFrame: 12 weeks
measure: Fasting blood potassium concentration
timeFrame: 12 weeks
measure: Fasting blood bicarbonates concentration
timeFrame: 12 weeks
measure: Fasting blood calcium concentration
timeFrame: 12 weeks
measure: Fasting blood inorganic phosphate concentration
timeFrame: 12 weeks
measure: Urine aspect
timeFrame: 12 weeks
measure: Urine color
timeFrame: 12 weeks
measure: Urinary density level
timeFrame: 12 weeks
measure: Urinary bilirubin level
timeFrame: 12 weeks
measure: Urinary urobilirubinogen level
timeFrame: 12 weeks
measure: Urinary protein level
timeFrame: 12 weeks
measure: Urinary glucose level
timeFrame: 12 weeks
measure: Urinary ketones level
timeFrame: 12 weeks
measure: Urinary nitrites level
timeFrame: 12 weeks
measure: Urine sediment
timeFrame: 12 weeks
measure: Urine osmolality
timeFrame: 12 weeks
measure: Urine pH
timeFrame: 12 weeks
measure: Urinary red cells level
timeFrame: 12 weeks
measure: Urinary white cells level
timeFrame: 12 weeks
Locations:
city: Lille
country: France
facility: Naturalpha
city: Saint-Herblain
country: France
facility: Biofortis
Study officials:
affiliation: BioFortis
name: David Gendre, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: AB-BIOTICS
name: Ariana Salavert, Ph. D.
role: STUDY_DIRECTOR
References: