Clinical trial NCT06959043: Therapeutic Strategies for Type 2 Diabetes Based on Lifestyle Changes: Plant-based Diet and Physical Exercise
Official title: Therapeutic Strategies for Type 2 Diabetes Based on Lifestyle Changes: Plant-based Diet and Physical Exercise
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Type 2 Diabetes Mellitus (T2DM)
Insulin Resistance
Inflamation
Gut Microbiomes
Keywords: Type 2 Diabetes Mellitus
Insulin Resistance
Inflamation
Metabolic Syndrome
Physical Exercise
Gut Microbiome
Plant-based Diet
Lifestyle Interventions
Lead sponsor: University of Sao Paulo General Hospital
Sponsor class: OTHER
Collaborators: name: Clínica e Spa Vida Natural
name: Probiotical Spa
name: CNPq - National Council for Scientific and Technological Development
First posted: 2025-05-06
Enrollment: 60
Sex: ALL
Minimum age (years): 45
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a double-blind, placebo-controlled, randomized clinical trial. Patients will be informed about the type of therapy they will receive at the clinic, which includes a strict vegetarian diet and regular physical exercises, as well as the importance of adhering strictly to the prescribed instructions.

A total of 60 patients will be recruited, with a maximum of six participants per four-week cycle. They will be randomized and allocated to the following treatment groups:

Group 1: Strict vegetarian diet (SVD) + regular physical exercise (RPE) (n=30). Group 2: SVD + RPE + administration of a probiotic pool (n=30).
Primary purpose: TREATMENT

Brief summary: The study evaluates the impact of a strict vegetarian diet combined with regular physical exercise and the use of probiotics on metabolic, inflammatory, and epigenetic parameters in patients with type 2 diabetes. It aims to determine the influence of these interventions on gut microbiota, glycemic control, body composition, insulin resistance, and quality of life.

Detailed description: This randomized, double-blind, placebo-controlled clinical trial aims to evaluate the effects of a strict vegetarian diet (SVD) combined with regular physical exercise (RPE), with or without probiotic supplementation, on key metabolic and physiological parameters in patients with type 2 diabetes mellitus (T2DM). Participants will be monitored for changes in glycemic control, insulin resistance (IR), liver function (elastography and ultrasound), metabolomic profile, muscle composition (biopsy), cholesterol efflux, and gene expression.

Glycemic Control Glycemic control will be assessed through glycated hemoglobin (HbA1c), fasting glucose, fructosamine, and oral meal tolerance test (OMTT). A standardized dietary test (500 kcal plant-based meal) will be conducted at baseline and post-intervention, measuring postprandial glucose, insulin, proinsulin, C-peptide, and incretin hormones (GLP-1, GIP).

Insulin Resistance (IR) IR will be evaluated using HOMA-IR (Homeostatic Model Assessment of Insulin Resistance) and fasting insulin levels. The study will also analyze inflammatory markers (TNF-α, IL-1β, IL-6, IFN-γ), as chronic low-grade inflammation plays a crucial role in IR development.

Elastography and Ultrasound (US) Liver ultrasound and transient elastography (FibroScan®) will be performed to assess hepatic steatosis and fibrosis, which are highly prevalent in T2DM. The effects of dietary and probiotic interventions on liver fat content, liver stiffness, and metabolic liver function will be analyzed.

Metabolome Analysis Metabolomic profiling will be conducted through mass spectrometry-based analysis of fasting and postprandial plasma samples. The study will evaluate amino acids, lipids, short-chain fatty acids, bile acids, ketone bodies, and glycolysis-related metabolites to understand how dietary and microbiome changes influence metabolic pathways in T2DM.

Muscle Biopsy A vastus lateralis muscle biopsy will be performed in a subgroup of participants (n=24). Samples will be analyzed for fiber composition, extracellular matrix remodeling, mitochondrial function, and inflammatory markers. The role of microRNAs (miR-29a, miR-29b, miR-1, miR-133a/b, miR-206) in muscle insulin sensitivity will also be investigated.

Cholesterol Efflux HDL functionality will be assessed by measuring cholesterol efflux capacity from macrophages exposed to participants' serum. This analysis will provide insight to cardiovascular risk modulation by diet and probiotics in T2DM.

Gene Expression Analysis Peripheral blood lymphocytes will be analyzed for expression of inflammation-related genes (TNF-α, IL-6, IL-1β, IFN-γ, TLR4, TLR5) and longevity-related genes (SIRT1, FOXO1, PGC-1α, P53). These markers will help determine how dietary and probiotic interventions influence immune response, cellular aging, and metabolic regulation.

Microbiota analysis This study will assess how a strict vegetarian diet and probiotic supplementation influence gut microbiota composition and functionality in individuals with T2DM. Stool samples will be collected before and after the intervention (4 weeks) and analyzed using 16S rRNA sequencing (NGS platforms: Ion Torrent PGM or Illumina MiSeq).

Microbiota diversity (alpha and beta diversity metrics) and the relative abundance of key bacterial taxa (Bacteroides, Firmicutes, Akkermansia, Prevotella, Bifidobacterium, Lactobacillus) will be evaluated. Functional analysis will include metagenomic predictions (PICRUSt2), short-chain fatty acid (SCFA) production, and microbial metabolic pathways.

The impact of probiotic supplementation (B. breve BR03, B. breve B632, B. longum 04, L. reuteri LRE11) will be assessed by comparing gut microbiota changes between the probiotic and placebo groups, focusing on butyrate-producing bacteria, lactate-utilizing species, and intestinal barrier integrity markers.

The intervention will last four weeks, followed by 12 months of telemedicine follow-up. This study aims to provide new insights into the role of lifestyle interventions in metabolic regulation, inflammation, and gut microbiota modulation in T2DM, potentially offering novel therapeutic strategies beyond pharmacological approaches.

Eligibility criteria: Inclusion Criteria:

* Have a medical diagnosis of type 2 diabetes for a maximum of 5 years.
* Be omnivorous; Have a Body Mass Index (BMI) ≥ 25 kg/m2 and \< 40 kg/m2;
* Be between the ages of 45 and 70, both genders.
* Women should be in the postmenopausal stage;
* Use no more than three hypoglycemic medications in total;
* Have the availability for a four-week consecutive hospitalization at CSVN.

Exclusion Criteria:

* Be using insulin, anti-obesity medications, antibiotics, and/or probiotic supplements in the 2 months preceding data collection;
* Use of alcohol or tobacco;
* Have limited mobility and a previous diagnosis of cardiopulmonary diseases;
* Report current or previous (within the past two months) diarrhea during screening;
* Have liver or kidney failure and uncontrolled endocrine disorders (hypothyroidism, hypogonadism, and adrenal insufficiency);
* Have eating disorders or have undergone bariatric surgery.

Primary outcomes:
measure: Change in Body Mass Index (BMI)
timeFrame: Baseline and 4 weeks post-intervention
measure: Change in Waist, Abdominal, and Hip Circumference
timeFrame: Baseline and 4 weeks post-intervention
measure: Change in Waist-to-Hip Ratio (WHR)
timeFrame: Baseline and 4 weeks post-intervention
measure: Change in Functional Aerobic Capacity (1-Mile Walk Test)
timeFrame: Baseline and 4 weeks post-intervention
measure: Change in Functional Mobility (Up and Go Test)
timeFrame: Baseline and 4 weeks post-intervention
measure: Change in Fasting Blood Glucose
timeFrame: Baseline and 4 weeks post-intervention
measure: Change in Postprandial Glucose Levels
timeFrame: Baseline and 4 weeks post-intervention
measure: Change in Glycated Hemoglobin (HbA1c)
timeFrame: Baseline and 4 weeks post-intervention
Secondary outcomes:
measure: Change in Liver Enzymes (AST, ALT, GGT)
timeFrame: Baseline and 4 weeks post-intervention
measure: Change in Standard Lipid Profile
timeFrame: Baseline and 4 weeks post-intervention
measure: HDL Function and Lipid Profile
timeFrame: Baseline and 4 weeks post-intervention
measure: Change in C-Reactive Protein (CRP) Levels
timeFrame: Baseline and 4 weeks post-intervention
measure: Change in Plasma Cytokine Levels
timeFrame: Baseline and 4 weeks post-intervention
measure: Metabolomic and Biochemical Markers
timeFrame: Baseline and 4 weeks post-intervention
measure: Change in expression of Metabolism- and Inflammation-Related microRNAs
timeFrame: Baseline and 4 weeks post-intervention
measure: Change in Expression of Inflammatory Genes
timeFrame: Baseline and 4 weeks post-intervention
measure: Change in Inflammatory Gene Expression in Lymphocytes and Skeletal Muscle
timeFrame: Baseline and 4 weeks post-intervention
measure: Change in Fasting Insulin, Proinsulin, and C-Peptide Levels
timeFrame: Baseline and 4 weeks post-intervention
measure: Change in Insulin Resistance Assessed by HOMA-IR
timeFrame: Baseline and 4 weeks post-intervention
measure: Change in Incretin Hormone Levels (GLP-1 and GIP)
timeFrame: Baseline and 4 weeks post-intervention
measure: Changes in Gut Microbiota Composition
timeFrame: Baseline and 4 weeks post-intervention
measure: Change in Liver Steatosis Assessed by Abdominal Ultrasound
timeFrame: Baseline and 4 weeks post-intervention
measure: Change in Liver Fat and Fibrosis Assessed by Transient Elastography
timeFrame: Baseline and 4 weeks post-intervention
measure: Change in Depressive Symptoms Measured by the Beck Depression Inventory - Second Edition (BDI-II)
timeFrame: Baseline and 12 weeks post-intervention
measure: Change in Diabetes-Specific Quality of Life Measured by the Diabetes Quality of Life Measure (DQOL)
timeFrame: Baseline and 12 weeks post-intervention
measure: Change in General Well-Being Measured by the Q8RN Questionnaire
timeFrame: Baseline and 12 weeks post-intervention
measure: Change in Fasting Glucose During Telemedicine Follow-Up
timeFrame: Every 3 months over a 12-month follow-up period after the intervention
measure: Change in HbA1c Levels During Telemedicine Follow-Up
timeFrame: Every 3 months over a 12-month follow-up period after the intervention
measure: Change in Lipid Profile During Telemedicine Follow-Up
timeFrame: Every 3 months over a 12-month follow-up period after the intervention
measure: Change in Liver Enzymes During Telemedicine Follow-Up
timeFrame: Every 3 months over a 12-month follow-up period after the intervention
Other outcomes:
Locations:
city: São Paulo
country: Brazil
facility: Universidade de São Paulo (USP)
Study officials:
affiliation: University of Sao Paulo
name: Maria E. R. Silva, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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