The Effect of a Bifidobacterium and Polydextrose on Body Fat Mass

Study Overview
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Brief Summary
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Obesity is a major problem worldwide, and it is related to abnormalities in glucose and lipid metabolism. The purpose of this study is to investigate the effect of a dietary supplement containing probiotic (Bifidobacterium animalis ssp. lactis 420) and/or prebiotic (Litesse) on change in body fat mass in a double-blind, randomized, placebo-controlled intervention trial. The supplement is ingested once per day for the duration of six months, and participants will attend a follow-up visit one month after the end of the intervention. The study will enroll 232 participants (58 per study arm) in four research centers in southern Finland.

Detailed Description
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Obesity is a major problem worldwide, and it is related to abnormalities in glucose and lipid metabolism. Preclinical studies have shown that weight gain and insulin resistance may be prevented by oral administration of the probiotic Bifidobacterium animalis ssp. lactis 420. Furthermore, the prebiotic polydextrose has shown efficacy on satiety in clinical settings. The purpose of this study is to investigate the effects of these products, individually and combined, on change in body fat mass in a double-blind, randomized, placebo-controlled intervention trial. The study is conducted at four research clinics in southern Finland. The supplement is provided in a sachet, mixed into a fruit smoothie and ingested once per day for the duration of six months. One month from the end of the intervention participants will attend a follow-up visit. The study will enroll 232 participants, who will be randomized into blocks using a computerized procedure. After the screening visit, there will be seven study visits (once per month) and one follow-up visit. Visits at months 0, 2, 4, 6 and follow-up are clinic visits, and visits at months 1, 3 and 5 are phone contacts to check compliance and any adverse events. Clinic visits include the following measurements and samples: weight blood pressure and heart rate blood samples returning of food diaries (only during intervention) returning of exercise questionnaires and food choice questionnaires (only beginning and end of treatment) returning of fecal samples, taken at home by participant DXA for body composition analysis hip and waist circumference brief physical examination (only beginning and end of treatment) recording of adverse events and concomitant medication For compliance check, unused sachets are returned to the clinic and counted. At the follow-up visit participants will receive guidance on exercise and a healthy diet. The primary variable of this study is relative change from baseline to end-of-treatment in body fat mass. Comparisons between each of the active groups against the placebo group will be performed if the global P-value is significant. Secondary variables will be analyzed in a similar fashion. The relative and absolute changes in body fat mass will also be analyzed. To explore the mechanism of potential treatment benefits, post-hoc responder analyses may optionally be performed. Also, correlations between the response variables may be examined in exploratory analyses. Post-hoc analyses may be conducted to compare e.g. different time points or to analyze differences from end-of-treatment to follow-up.

Official Title
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The Effect of Separate or Combined Supplementation of Probiotic (Bifidobacterium Lactis B420) and Polydextrose on Body Fat Mass

Conditions
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Obesity, Hyperglycemia, Insulin Resistance

Intervention / Treatment
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* Dietary Supplement: Bifidobacterium animalis ssp. lactis 420
* Dietary Supplement: Polydextrose
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI between 28.0-34.9 Waist to hip ratio: males ≥0.88, females ≥0.83 Age 18-65 years Signed informed consent Available for all study visits and phone calls Follows a regular diet that is in agreement with the national dietary recommendations Exclusion Criteria: Diagnosed type 1 or type 2 diabetes (i.e. fasting plasma glucose ≥ 7 mmol/l and HbA1C ≥ 6.5%) Use of medication for diabetes, dyslipidemia or hypertension Use of laxatives or fiber supplements in the past 6 weeks History of diagnosed coronary heart disease, other significant cardiovascular disease or artificial heart valve History of chronic active inflammatory disorders History of bariatric surgery Use of anti-obesity drugs in the last 3 months Use of anticoagulants Regular use of non-steroidal anti-inflammatory drugs, systemic or inhaled corticosteroids, or systemic immunomodulatory drugs Recent (last 2 months) or ongoing antibiotic use Immunosuppression or ongoing therapy causing immunosuppression Use of probiotics more than once a week during the previous 6 weeks Use of vitamin D supplementation: > 50 - <100 µg/day during the previous 2 weeks ≥ 100 - <150 µg/day during the previous 2 months ≥150 µg/day or above during the previous 12 months Active or recent (last 3 months) participation in a weight loss program or weight change (increase or loss) of 3 kg during the past 3 months Pregnant or planning pregnancy within 6 months or breastfeeding women Participation in a clinical trial with an investigational product or drug within 60 days prior to screening Likeliness to be noncompliant with the protocol Drug or alcohol abuse Allergy to any of the ingredients used in the study Other reasons that, in the opinion of the Investigator makes the subject unsuitable for enrolment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Probiotic<br>Bifidobacterium animalis ssp. lactis 420 (10^10 colony-forming units (CFU)/day in 12 g of microcrystalline cellulose), once per day for six months in a sachet mixed into a smoothie drink | Dietary Supplement: Bifidobacterium animalis ssp. lactis 420<br>* Studied as a probiotic bacteria<br>* Other names: B420;|
| Active Comparator: Prebiotic<br>Polydextrose, 12 g once per day for six months in a sachet mixed into a smoothie drink | Dietary Supplement: Polydextrose<br>* Studied as a prebiotic<br>* Other names: Litesse Ultra;|
| Active Comparator: Synbiotic<br>B. lactis 420 (10^10 CFU/day) in 12 g of polydextrose, once per day for six months in a sachet to be mixed into a smoothie drink | Dietary Supplement: Bifidobacterium animalis ssp. lactis 420<br>* Studied as a probiotic bacteria<br>* Other names: B420;Dietary Supplement: Polydextrose<br>* Studied as a prebiotic<br>* Other names: Litesse Ultra;|
| Placebo Comparator: Control<br>12 g of microcrystalline cellulose once per day for six months in a sachet to be mixed into a smoothie drink | Other: Placebo<br>* Control<br>* Other names: Microcrystalline cellulose;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in body fat mass from baseline to end-of-treatment (6 months) | Measured with dual-energy x-ray absorptiometry (DXA) | From baseline to end of intervention (6 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in weight (absolute and relative) |  | Months 0, 2, 4, 6 and 7 (follow-up) | 
| Change in BMI (absolute and relative) |  | Months 0, 2, 4, 6 and 7 (follow-up) | 
| Change in lean body mass | Total, and in individual regions of the body | Months 0, 2, 4, 6 and 7 (follow-up) | 
| Hip Change in waist and/or hip circumference (absolute and relative) |  | Months 0, 2, 4, 6 and 7 (follow-up) | 
| Change in glycated haemoglobin (HbA1c) in blood |  | Months 0, 2, 4, 6 and 7 (follow-up) | 
| Change in fasting glucose levels |  | Months 0, 2, 4, 6 and 7 (follow-up) | 
| Change in fasting insulin levels |  | Months 0, 2, 4, 6 and 7 (follow-up) | 
| Change in insulin resistance | As determined by Homeostasis Model Assessment (HOMA) | Months 0, 2, 4, 6 and 7 (follow-up) | 
| Change in inflammatory markers | Including high-sensitive C-reactive protein (CRP), Interleukin (IL)-6, Tumor necrosis factor (TNF)-alpha, IL-1beta, cortisol, adiponectin, leptin | Months 0, 2, 4, 6 and 7 (follow-up) | 
| Change in lipopolysaccharide (LPS) concentration and soluble CD14 (sCD14) |  | Months 0, 2, 4, 6 and 7 (follow-up) | 
| Change in LPS/sCD14 ratio |  | Months 0, 2, 4, 6 and 7 (follow-up) | 
| Change in blood lipids | Total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides | Months 0, 2, 4, 6 and 7 (follow-up) | 
| Change in blood pressure |  | Months 0, 2, 4, 6 and 7 (follow-up) | 
| Change in aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT) and gamma-glutamyltransferase |  | Months 0, 2, 4, 6 and 7 (follow-up) | 
| Change in energy, fat and fiber intake |  | Months 0, 2, 4, 6 and 7 (follow-up) | 
| Absolute change in body fat mass |  | Months 0, 2, 4, 6 and 7 (follow-up) | 
| Analytical description of faecal microbiota |  | Months 0, 2, 4, 6 and 7 (follow-up) | 
| Body fat mass in individual regions of the body |  | Months 0, 2, 4, 6 and 7 (follow-up) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Blood glucose, Waist circumference, Lipid metabolism, Probiotics, Prebiotics, Dietary supplements, Endotoxemia