Effect of Probiotic Supplementation on Fecal Microbiota, Nutritional Status, Metabolic and Inflammatory Parameters in Patients With Type 2 Diabetes Mellitus: Study Protocol for a Triple-blind Controlled Randomized Clinical Trial
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Enrollment
- 80
- Locations
- 2
- Primary Endpoint
- SCFA
Study Overview
Brief Summary
The purpose of this study is to evaluate the effect of probiotic supplementation on fecal microbiota, nutritional status, metabolic and inflammatory parameters in patients with type 2 diabetes mellitus.
Study hypothesis: Supplementation of multispecies probiotic (Bifidobacterium Lactis, B. brebe, B. longum, Lactobacillus gasseri, L. casei, L. rhamnosus) during 12 weeks improves the the fecal microbiota composition and promotes reduction of plasma/serum levels of acute phase proteins, cytokines, metabolic and anthropometric parameters in individuals with type 2 diabetes mellitus.
Detailed Description
The purpose of this study is to evaluate the effect of multispecies probiotic supplementation (specifically designed for the present study) on fecal microbiota, nutritional status, metabolic and inflammatory parameters in patients with type 2 diabetes mellitus (T2DM).
Adult individuals (35 to 75 years old) of both sexes with T2DM (diagnosed at least 1 year ago), body mass index from 25.00 kg/m² to 39.99 kg/m², glycated hemoglobin ≤ 9.0% and using metformin will be invited to participate in this randomized, placebo-controlled, triple-blind study.
The participants will be randomized into two groups: G1 - probiotic group and G2 - control group (placebo).
The study will consist of two experimental time points: M0 - baseline and start of supplementation; M1 - after 12 weeks of the first outpatient visit and start of supplementation.
In the two experimental moments, individual fecal samples will be obtained for analysis of the fecal microbiota; The metabolic parameters will be assessed by determination of circulating levels of SCFA, FFA, insulin, fasting glucose and glycated hemoglobin, HOMA-IR; Total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides; the inflammatory response will be assessed by determination of plasma indicadors (LPS, Adiponectina, IL-10, IL-1, IL-6, TNF- α, Leptina, Resistina) ; besides the evaluation of indicators of nutritional status (bone densitometry with body composition and anthropometric measurements).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
Study participants and researchers were masked over consumption and distribution of supplementation, respectively.
Laboratory technicians who performed the blood collection were also masked as to the distribution of supplementation.
Supplements and placebo were pre-packaged by the supplier in opaque and closed sachets with randomization codes, being identical in physical appearance, taste and color. Supplement identification codes were only disclosed by the supplier after statistical analysis of study data.
Eligibility Criteria
- Ages
- 35 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age from 35 to 75 years old;
- •Individuals diagnosed with type 2 diabetes mellitus (at least 1 year ago);
- •Body mass index from 25.00 kg/m² to 39.99 kg/m²;
- •Glycated hemoglobin ≤ 9.0% ;
- •Using metformin, combined or not with other antidiabetic drugs
Exclusion Criteria
- •Previous bowel diseases (inflammatory bowel disease and irritable bowel syndrome); or previous gastrointestinal surgery (eg, colectomy, gastrectomy)
- •Intolerances and ∕ or food allergies with a previous medical diagnosis (eg lactose intolerance or celiac disease);
- •Glomerular filtration rate <30 ml/min/1.73m²; inflammatory diseases and immunodeficiencies;
- •Diagnosis of autonomic neuropathy with gastrointestinal involvement such as: diabetic gastroparesis, diabetic enteropathy (diarrhea) or colonic hypomotility (constipation);
- •Hospital admission and/or use of anti-inflammatory drugs (non-hormonal and corticosteroids) up to 1 month before the study; and ∕or use of antibiotics up to 3 months before the study;
- •Regular use of laxatives, opioid narcotic analgesics or appetite suppressants;
- •Current or previous use (up to 1 month) of prebiotics, probiotics, symbiotics or products enriched with these food supplements;
- •Intolerance to prebiotics, probiotics or symbiotics;
- •Pregnant or breastfeeding;
- •Follow-up of a diet, guided by a nutritionist, for weight loss or gain up to 1 month before the study or current follow-up of unusual diets (eg vegetarian, macrobiotic, paleolithic);
- •Alcohol consumption (> 1 drink/day or 14g of alcohol for women; >2 drinks/day or 28 grams of alcohol for men); use of illicit drugs and smokers;
- •Change of lipid-lowering and/or antidiabetic drugs in the last 3 months
Outcomes
Primary Outcomes
SCFA
Time Frame: 12 weeks compared to baseline
Acetate, propionate, isobutyrate, butyrate and isovalerate (μmol/L)
Inflammatory parameters
Time Frame: 12 weeks compared to baseline
Plasma LPS, adiponectin, leptin, resistin, IL-1, IL-6, IL-8, IL-10 and TNF-alpha concentrations (pg/mL)
Fecal Microbiota
Time Frame: 12 weeks compared to baseline
analysis method: 16s rRNA sequencing and bioinformatics analysis. Reported measure: taxonomic profiles of the microbial populations (operational taxonomic units / OTUs)
Secondary Outcomes
- Free Fat Acids(12 weeks compared to baseline)
- fasting blood glucose(12 weeks compared to baseline)
- HOMA-IR(12 weeks compared to baseline)
- LDL-c(12 weeks compared to baseline)
- Bone densitometry(12 weeks compared to baseline)
- Glycated hemoglobin(12 weeks compared to baseline)
- Triglycerides(12 weeks compared to baseline)
- Fasting insulin(12 weeks compared to baseline)
- Body mass index (BMI)(12 weeks compared to baseline)
- Total cholesterol(12 weeks compared to baseline)
- HDL-c(12 weeks compared to baseline)
- Total Body Fat Percentage (%BF)(12 weeks compared to baseline)
- Body weight (kg)(12 weeks compared to baseline)
- Waist circumference (cm)(12 weeks compared to baseline)
- Fat Mass Index (FMI)(12 weeks compared to baseline)
- Total Body lean mass Percentage (%)(12 weeks compared to baseline)
Investigators
Erasmo Benicio Santos de Moraes Trindade
Professor
Universidade Federal de Santa Catarina