Investigation of the Effects of a Bifidobacterium Breve Strain on Fat Loss in Healthy Adults

Study Overview
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Brief Summary
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Overweight has become a critical issue in North America and the market value of weight loss products is expected to rise as the population becomes more health-conscious and aware of the risks associated with excess body weight. This randomized, placebo-controlled, clinical trial investigates the effect of Bifidobacterium breve supplementation with exercise intervention on fat loss.

Detailed Description
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In early adulthood, excess body weight is a risk factor associated with several health complications later on in life and probiotics have been used for decades for maintaining intestinal health, and in recent years probiotics have been proposed for weight management. This randomized, placebo-controlled, clinical trial investigates the effect of Bifidobacterium breve supplementation with exercise intervention on fat loss.

Official Title
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A Randomized, Double-blind, Placebo-controlled Study to Investigate the Effects of a Bifidobacterium Breve Strain on Fat Loss in Healthy Adults

Conditions
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Obesity, Overweight and Obesity

Intervention / Treatment
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* Dietary Supplement: B. breve
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female between 20 and 65 years of age, inclusive BMI from 25.0 to 29.9 kg/m2, inclusive Female participants are not of child-bearing potential, defined as females who have undergone a sterilization procedure (e.g. hysterectomy, bilateral oophorectomy, bilateral tubal ligation, complete endometrial ablation) or have been post-menopausal (natural or surgically) for at least 1 year prior to screening Or, Females of child-bearing potential must have a negative baseline urine pregnancy test and agree to use a medically approved method of birth control for the duration of the study. All hormonal birth control must have been in use for a minimum of three months. Acceptable methods of birth control include: Hormonal contraceptives including oral contraceptives, hormone birth control patch (Ortho Evra), vaginal contraceptive ring (NuvaRing), injectable contraceptives (Depo-Provera, Lunelle), or hormone implant (Norplant System) Double-barrier method Intrauterine devices Non-heterosexual lifestyle or agrees to use contraception if planning on changing to heterosexual partner(s) Vasectomy of partner at least 6 months prior to screening Self-reported stable body weight for the past 3 months defined as not having gained or lost more than 5 kg of body weight throughout the 3 months prior to baseline Participants with the following body fat percentages as determined by Bioelectrical Impedance Analysis (BIA): Female: ≥ 30% Male: ≥ 20% Agrees to follow the diet and exercise guidelines for the duration of the study Willingness to complete questionnaires, records, and diaries associated with the study, to complete all clinic visits, and provide stool samples Provide voluntary, written, informed consent to participate in the study Healthy as determined by medical history, laboratory results and physical exam as assessed by the Qualified Investigator (QI) Exclusion Criteria Women who are pregnant, breastfeeding or planning to become pregnant during the trial Allergy, sensitivity, or intolerance to the investigational product's active or inactive ingredients Clinically significant abnormal laboratory results at screening as assessed by the QI Current or history of any significant gastrointestinal disease requiring medication (e.g. GERD, gastroenteritis) Irregular sleep schedule Chronic diarrhea or constipation Participants with hypertension and are on antihypertensive medication Type I or Type II diabetes Participants with hyperlipidemia and are on medication Self-reported sleep apnea Self-reported current or pre-existing thyroid condition. Treatment on a stable dose of medication for at least 3 months will be considered by the QI Unstable metabolic disease or chronic diseases as assessed by the QI History of or current diagnosis with kidney and/or liver diseases as assessed by the QI on a case-by-case basis, with the exception of history of kidney stones in participants who are symptom-free for 6 months Significant cardiovascular event in the past 6 months. Participants with no significant cardiovascular event on stable medication may be included after assessment by the QI on a case by case basis Major surgery in the past 3 months or individuals who have planned surgery during the trial period. Participants with minor surgery will be considered on a case-by-case basis by the QI Cancer, except skin cancers completely excised with no chemotherapy or radiation with a follow up that is negative. Volunteers with cancer in full remission for more than five years after diagnosis are acceptable Individuals with an autoimmune disease or are immune-compromised Self-reported HIV-, Hepatitis B- and/or C-positive diagnosis Blood/bleeding disorders as determined by laboratory results Self-reported mental or neuropsychological condition and/or cognitive impairment that, in the QI's opinion, could interfere with study participation Metal implants that may affect the DXA scan results will be assessed on a case- by-case basis by the QI. Current use of prescribed medications listed in Section Prescribed Medications as follows: Beta-blockers and thiazide diuretics (within 4 weeks of baseline) Weight loss medication (within 4 weeks of baseline) Lipid-lowering medications (within 4 weeks of baseline) Anticoagulants and coagulants (within 4 weeks of baseline) Sleep medication Selective serotonin reuptake inhibitors (SSRI) Antibiotics Non-steroidal anti-inflammatory drugs (NSAIDs) Proton pump inhibitors (PPIs) Metformin (unless on a stable dose for the last 6 months) Current use of over-the-counter medications, supplements, foods and/or drinks as follows: OTC NSAIDs (PRN use is acceptable) OTC blood pressure medication or supplements (within 4 weeks of baseline) Lipid metabolising supplements (within 4 weeks of baseline) Fish oil and omega-3 supplements Red yeast rice Plant sterols and stanols OTC medication or supplements marketed for weight loss (within 4 weeks of baseline) Vitamin E supplements (within 4 weeks of baseline) Coagulant/anticoagulant supplements (within 4 weeks of baseline) PPIs Use of cannabinoid products within 60 days of baseline. History of cannabis used will be assessed on a case by case basis by the QI Use of tobacco products within 60 days of baseline Self-reported alcohol or drug abuse within the last 12 months High alcohol intake (average of > 2 standard drinks per day or > 10 per week) Current employment that calls for shift work or have worked shift work in the last 3 weeks Participation in other clinical research trials 30 days prior to screening Blood donation 30 days prior to screening, during the study, or a planned donation within 30-days of the last study visit Individuals who are unable to give informed consent Any other condition, that, in the opinion of the QI, may adversely affect the participant's ability to complete the study or its measures, or which may pose a significant risk to the participant

Ages Eligible for Study
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Minimum Age: 20 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo delivered in capsule format. Participants will be instructed to take 2 capsules of placebo for 4 weeks during the run-in period. On day 1 participants will be instructed to take 2 capsules of placebo in the morning before breakfast for 12 weeks. | Dietary Supplement: Placebo<br>* Placebo capsule. Participants will be instructed to take 2 capsules of placebo for 4 weeks during the run-in period. On day 1 participants will be instructed to take 2 capsules of placebo in the morning before breakfast for 12 weeks.<br>|
| Experimental: B. breve<br>Capsule containing B breve. Participants will be instructed to take 2 capsules of placebo for 4 weeks during the run-in period. On day 1 participants will be instructed to take 2 capsules of B. breve B-3 in the morning before breakfast for 12 weeks. | Dietary Supplement: B. breve<br>* Probiotic capsule. Participants will be instructed to take 2 capsules of placebo for 4 weeks during the run-in period. On day 1 participants will be instructed to take 2 capsules of B. breve B-3 in the morning before breakfast for 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Fat loss | The difference in change in fat loss from baseline (% or g), as assessed by Dual-Energy X-Ray Absorptiometry (DXA), between B. breve and placebo after 12 weeks of supplementation. Body tissue density will be measured by a form of X-ray radiation and converted into body fat and muscle mass percentage for assessment | 12 weeks from baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body weight | The difference in change from baseline between B. breve and placebo in body weight after 12 weeks of supplementation | 12 weeks from baseline | 
| BMI | The difference in change from baseline between B. breve and placebo in BMI after 12 weeks of supplementation | 12 weeks from baseline | 
| Android/gynoid fat ratio | The difference in change from baseline between B. breve and placebo in android/gynoid fat ratio as assessed by DXA after 12 weeks of supplementation. Android-gynoid percent fat ratio is a pattern of body fat distribution that is associated with an increased risk for metabolic syndrome in healthy adults. | 12 weeks from baseline | 
| Muscle mass | The difference in change from baseline between B. breve and placebo in muscle mass as assessed by DXA after 12 weeks of supplementation. | 12 weeks from baseline | 
| Waist circumference | The difference in change from baseline between B. breve and placebo in Waist circumference after 6 and 12 weeks of supplementation. | Baseline, 6 weeks and 12 weeks | 
| Hip circumference | The difference in change from baseline between B. breve and placebo in hip circumference after 6 and 12 weeks of supplementation. | Baseline, 6 weeks and 12 weeks | 
| Waist/hip circumference ratio | The difference in change from baseline between B. breve and placebo in waist/hip circumference ratio after 6 and 12 weeks of supplementation. | Baseline, 6 weeks and 12 weeks | 
| Microbiota composition analysis | The change from baseline between B. breve and placebo in microbiota composition after 12 weeks of supplementation. | 12 weeks from baseline | 
| Body composition | The change from baseline between B. breve and placebo in body composition ( this takes into account such parameters as weight, BMI, total body fat (% or g), android fat (% or g), gynoid fat (% or g), android/gynoid fat ratio, and muscle mass (% or g) and waist circumference, hip circumference, and waist/hip circumference ratio) in participant groups classified by microbiota composition at week 0, after 12 weeks of supplementation. These individual outcomes comprise relevant aspects of body composition. Each outcome will be analyzed separately and interpreted separately as well as collectively to inform relevant changes to body composition as a whole during the study. | 12 weeks from baseline | 
| Total cholesterol | The difference in change from baseline between B. breve and placebo in total cholesterol after 12 weeks of supplementation. | Baseline and 12 weeks of supplementation | 
| HDL-cholesterol | The difference in change from baseline between B. breve and placebo in HDL-cholesterol after 12 weeks of supplementation. | Baseline and 12 weeks of supplementation | 
| LDL-cholesterol | The difference in change from baseline between B. breve and placebo in LDL-cholesterol after 12 weeks of supplementation. | Baseline and 12 weeks of supplementation | 
| Triglycerides | The difference in change from baseline between B. breve and placebo in triglycerides after 12 weeks of supplementation. | Baseline and 12 weeks of supplementation | 
| Fasting blood glucose | The difference in change from baseline between B. breve and placebo in fasting blood glucose after 12 weeks of supplementation. | Baseline and 12 weeks of supplementation | 
| HbA1c | The difference in change from baseline between B. breve and placebo in HbA1c after 12 weeks of supplementation. | Baseline and 12 weeks of supplementation | 
| Fasting insulin | The difference in change from baseline between B. breve and placebo in fasting insulin after 12 weeks of supplementation. | Baseline and 12 weeks of supplementation | 
| Alkaline phosphatase (ALP) | The difference in change from baseline between B. breve and placebo in ALP after 12 weeks of supplementation. | Baseline and 12 weeks of supplementation | 
| Gamma-glutamyl transferase (GGT) | The difference in change from baseline between B. breve and placebo in GGT after 12 weeks of supplementation. | Baseline and 12 weeks of supplementation | 
| Alanine aminotransferase (ALT) | The difference in change from baseline between B. breve and placebo in ALT after 12 weeks of supplementation. | Baseline and 12 weeks of supplementation | 
| Aspartate transaminase (AST) | The difference in change from baseline between B. breve and placebo in AST after 12 weeks of supplementation. | Baseline and 12 weeks of supplementation | 
| Frequency of bowel movements | The difference in change from baseline between B. breve and placebo in Frequency of bowel movements after 6 and 12 weeks of supplementation. | Baseline, 6 and 12 weeks of supplementation |