Clinical trial NCT01978691: The Effect of a Bifidobacterium and Polydextrose on Body Fat Mass
Official title: The Effect of Separate or Combined Supplementation of Probiotic (Bifidobacterium Lactis B420) and Polydextrose on Body Fat Mass
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Obesity
Hyperglycemia
Insulin Resistance
Keywords: Obesity
Blood glucose
Waist circumference
Lipid metabolism
Probiotics
Prebiotics
Dietary supplements
Endotoxemia
Lead sponsor: Danisco
Sponsor class: INDUSTRY
First posted: 2013-11-07
Enrollment: 225
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: SUPPORTIVE_CARE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Difference in body fat mass from baseline to end-of-treatment (6 months)
timeFrame: From baseline to end of intervention (6 months)
Secondary outcomes:
measure: Change in weight (absolute and relative)
timeFrame: Months 0, 2, 4, 6 and 7 (follow-up)
measure: Change in BMI (absolute and relative)
timeFrame: Months 0, 2, 4, 6 and 7 (follow-up)
measure: Change in lean body mass
timeFrame: Months 0, 2, 4, 6 and 7 (follow-up)
measure: Hip Change in waist and/or hip circumference (absolute and relative)
timeFrame: Months 0, 2, 4, 6 and 7 (follow-up)
measure: Change in glycated haemoglobin (HbA1c) in blood
timeFrame: Months 0, 2, 4, 6 and 7 (follow-up)
measure: Change in fasting glucose levels
timeFrame: Months 0, 2, 4, 6 and 7 (follow-up)
measure: Change in fasting insulin levels
timeFrame: Months 0, 2, 4, 6 and 7 (follow-up)
measure: Change in insulin resistance
timeFrame: Months 0, 2, 4, 6 and 7 (follow-up)
measure: Change in inflammatory markers
timeFrame: Months 0, 2, 4, 6 and 7 (follow-up)
measure: Change in lipopolysaccharide (LPS) concentration and soluble CD14 (sCD14)
timeFrame: Months 0, 2, 4, 6 and 7 (follow-up)
measure: Change in LPS/sCD14 ratio
timeFrame: Months 0, 2, 4, 6 and 7 (follow-up)
measure: Change in blood lipids
timeFrame: Months 0, 2, 4, 6 and 7 (follow-up)
measure: Change in blood pressure
timeFrame: Months 0, 2, 4, 6 and 7 (follow-up)
measure: Change in aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT) and gamma-glutamyltransferase
timeFrame: Months 0, 2, 4, 6 and 7 (follow-up)
measure: Change in energy, fat and fiber intake
timeFrame: Months 0, 2, 4, 6 and 7 (follow-up)
measure: Absolute change in body fat mass
timeFrame: Months 0, 2, 4, 6 and 7 (follow-up)
measure: Analytical description of faecal microbiota
timeFrame: Months 0, 2, 4, 6 and 7 (follow-up)
measure: Body fat mass in individual regions of the body
timeFrame: Months 0, 2, 4, 6 and 7 (follow-up)
Other outcomes:
measure: The differences between the treatment groups for exploratory variables
timeFrame: Throughout the 6-month study and 1-month follow-up
Locations:
city: Helsinki
country: Finland
facility: VL-Medi
city: Kerava
country: Finland
facility: Kerava healthcare center
city: Tampere
country: Finland
facility: FinnMedi Oy
city: Turku
country: Finland
facility: CRST - Clinical Research Services Turku
Study officials:
affiliation: HYKS-instituutti Oy
name: Aila Rissanen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.