The Effect of a Bifidobacterium and Polydextrose on Body Fat Mass

Phase 2

Completed

• Conditions: Hyperglycemia; Insulin Resistance; Obesity
• Interventions: Dietary Supplement: Polydextrose; Dietary Supplement: Bifidobacterium animalis ssp. lactis 420; Other: Placebo

• Registration Number: NCT01978691
• Lead Sponsor: Danisco

Brief Summary

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

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.

Study Timeline

• Study Start: 2013-11
• Study First Submitted: 2013-11-01
• Study First Submitted QC: 2013-11-01
• Study First Posted: 2013-11-07
• Primary Completion: 2015-05
• Study Completion: 2015-05
• Status Verified: 2016-02
• Last Update Submitted: 2016-02-01
• Last Update Posted: 2016-02-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 225

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:

  1. > 50 - <100 µg/day during the previous 2 weeks
  2. ≥ 100 - <150 µg/day during the previous 2 months
  3. ≥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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Prebiotic	Polydextrose	Polydextrose, 12 g once per day for six months in a sachet mixed into a smoothie drink
Probiotic	Bifidobacterium animalis ssp. lactis 420	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
Synbiotic	Bifidobacterium animalis ssp. lactis 420	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
Control	Placebo	12 g of microcrystalline cellulose once per day for six months in a sachet to be mixed into a smoothie drink
Synbiotic	Polydextrose	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

Primary Outcome Measures

Name	Time	Method
Difference in body fat mass from baseline to end-of-treatment (6 months)	From baseline to end of intervention (6 months)	Measured with dual-energy x-ray absorptiometry (DXA)

Secondary Outcome Measures

Name	Time	Method
Change in BMI (absolute and relative)	Months 0, 2, 4, 6 and 7 (follow-up)
Change in lean body mass	Months 0, 2, 4, 6 and 7 (follow-up)	Total, and in individual regions of the body
Change in fasting insulin levels	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 inflammatory markers	Months 0, 2, 4, 6 and 7 (follow-up)	Including high-sensitive C-reactive protein (CRP), Interleukin (IL)-6, Tumor necrosis factor (TNF)-alpha, IL-1beta, cortisol, adiponectin, leptin
Change in insulin resistance	Months 0, 2, 4, 6 and 7 (follow-up)	As determined by Homeostasis Model Assessment (HOMA)
Change in LPS/sCD14 ratio	Months 0, 2, 4, 6 and 7 (follow-up)
Change in blood lipids	Months 0, 2, 4, 6 and 7 (follow-up)	Total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides
Analytical description of faecal microbiota	Months 0, 2, 4, 6 and 7 (follow-up)
Change in weight (absolute and relative)	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 blood pressure	Months 0, 2, 4, 6 and 7 (follow-up)
Absolute change in body fat mass	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)
Body fat mass in individual regions of the body	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 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)

Trial Locations

Locations (4)

VL-Medi; 🇫🇮 Helsinki, Finland

Kerava healthcare center; 🇫🇮 Kerava, Finland

FinnMedi Oy; 🇫🇮 Tampere, Finland

CRST - Clinical Research Services Turku; 🇫🇮 Turku, Finland