The Effect of a Bifidobacterium and Polydextrose on Body Fat Mass (MetSProb)

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

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.

Study Overview

• Status: Completed
• Conditions: Hyperglycemia; Obesity; Insulin Resistance
• Intervention / Treatment: Dietary supplement: Bifidobacterium animalis ssp. lactis 420; Dietary supplement: Polydextrose; Other: Placebo

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 Type: Interventional
• Enrollment (Actual): 225
• Phase: Phase 2

Contacts and Locations

Study Locations

• Finland
  • Helsinki, Finland, 00101
    • VL-Medi
  • Kerava, Finland, 04200
    • Kerava healthcare center
  • Tampere, Finland, 33520
    • FinnMedi Oy
  • Turku, Finland, 20521
    • CRST - Clinical Research Services Turku

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Probiotic; 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; Studied as a probiotic bacteria; Other Names: B420
Active Comparator: Prebiotic; Polydextrose, 12 g once per day for six months in a sachet mixed into a smoothie drink	Dietary supplement: Polydextrose; Studied as a prebiotic; Other Names: Litesse; Litesse Ultra
Active Comparator: Synbiotic; 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; Studied as a probiotic bacteria; Other Names: B420; Dietary supplement: Polydextrose; Studied as a prebiotic; Other Names: Litesse; Litesse Ultra
Placebo Comparator: Control; 12 g of microcrystalline cellulose once per day for six months in a sachet to be mixed into a smoothie drink	Other: Placebo; Control; Other Names: Microcrystalline cellulose

What is the study measuring?

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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The differences between the treatment groups for exploratory variables	Fecal fat and/or energy content, change in plasma and fecal bile acids, plasma oxidated low-density lipoprotein cholesterol, LPS binding protein, Macrophage chemoattractant protein-1, Angiopoietin-like factor 4, Apolipoprotein B-48, Plasminogen activator inhibitor-1, Vascular cell adhesion molecule-1, Intercellular adhesion molecule-1, E-selectin, zonulin, blood microbiota	Throughout the 6-month study and 1-month follow-up

Collaborators and Investigators

• Sponsor: Danisco
• Investigators: Principal Investigator: Aila Rissanen, MD, HYKS-instituutti Oy

Publications and helpful links

General Publications

• Amar J, Chabo C, Waget A, Klopp P, Vachoux C, Bermudez-Humaran LG, Smirnova N, Berge M, Sulpice T, Lahtinen S, Ouwehand A, Langella P, Rautonen N, Sansonetti PJ, Burcelin R. Intestinal mucosal adherence and translocation of commensal bacteria at the early onset of type 2 diabetes: molecular mechanisms and probiotic treatment. EMBO Mol Med. 2011 Sep;3(9):559-72. doi: 10.1002/emmm.201100159. Epub 2011 Aug 3.
• Hibberd AA, Yde CC, Ziegler ML, Honore AH, Saarinen MT, Lahtinen S, Stahl B, Jensen HM, Stenman LK. Probiotic or synbiotic alters the gut microbiota and metabolism in a randomised controlled trial of weight management in overweight adults. Benef Microbes. 2019 Mar 13;10(2):121-135. doi: 10.3920/BM2018.0028. Epub 2018 Dec 10.
• Stenman LK, Lehtinen MJ, Meland N, Christensen JE, Yeung N, Saarinen MT, Courtney M, Burcelin R, Lahdeaho ML, Linros J, Apter D, Scheinin M, Kloster Smerud H, Rissanen A, Lahtinen S. Probiotic With or Without Fiber Controls Body Fat Mass, Associated With Serum Zonulin, in Overweight and Obese Adults-Randomized Controlled Trial. EBioMedicine. 2016 Nov;13:190-200. doi: 10.1016/j.ebiom.2016.10.036. Epub 2016 Oct 26.

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: November 1, 2013
• First Submitted That Met QC Criteria: November 1, 2013
• First Posted (Estimate): November 7, 2013

Study Record Updates

• Last Update Posted (Estimate): February 2, 2016
• Last Update Submitted That Met QC Criteria: February 1, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Obesity; Probiotics; Endotoxemia; Blood glucose; Waist circumference; Lipid metabolism; Prebiotics; Dietary supplements
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Hyperglycemia; Insulin Resistance
• Other Study ID Numbers: SMR-2782

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No