## Protocol Section
### Identification Module
**NCT ID:** NCT05418179

**Brief Title:** Effect of Probiotic Supplementation on Fecal Microbiota, Nutritional Status, Metabolic and Inflammatory Parameters in Patients With Type 2 Diabetes Mellitus

**Official Title:** 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

#### Organization Study ID Info
**ID:** UFSC_2021
#### Organization
**Class:** OTHER
**Full Name:** Universidade Federal de Santa Catarina
### Status Module
#### Completion Date
**Date:** 2023-12-24

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2023-03-28

**Type:** ACTUAL

**Last Update Submit Date:** 2023-03-27

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2023-12-20

**Type:** ESTIMATED

#### Start Date
**Date:** 2021-12-01

**Type:** ACTUAL

**Status Verified Date:** 2023-03

#### Study First Post Date
**Date:** 2022-06-14
**Type:** ACTUAL
**Study First Submit Date:** 2022-06-05
**Study First Submit QC Date:** 2022-06-12
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Universidade Federal de Santa Catarina

#### Responsible Party

**Investigator Affiliation:** Universidade Federal de Santa Catarina

**Investigator Full Name:** Erasmo Benicio Santos de Moraes Trindade

**Investigator Title:** Professor

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**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).

The primary endpoint will be the fecal microbiota composition, SCFA concentrations and the inflammatory parameters.

### Conditions Module

**Conditions:**

- Type 2 Diabetes Mellitus

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** QUADRUPLE

**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.

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 80

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Maltodextrin (1 capsule/day)

**Intervention Names:**

- Dietary Supplement: Placebo

**Label:** Placebo

**Type:** PLACEBO_COMPARATOR

#### Arm Group 2

**Description:** Probiotic (Bifidobacterium animalis subsp. Lactis, Bifidobacterium breve, Bifidobacterium longum, Lactobacillus gasseri, Lactobacillus casei, Lactobacillus rhamnosus) - 1 capsule/day

**Intervention Names:**

- Dietary Supplement: Probiotic

**Label:** Probiotic

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Probiotic

**Description:** Probiotic (Bifidobacterium animalis subsp. Lactis, Bifidobacterium breve, Bifidobacterium longum, Lactobacillus gasseri, Lactobacillus casei, Lactobacillus rhamnosus) - 1 capsule/day

**Name:** Probiotic

**Type:** DIETARY_SUPPLEMENT

#### Intervention 2

**Arm Group Labels:**

- Placebo

**Description:** Maltodextrin (1 capsule/day)

**Name:** Placebo

**Type:** DIETARY_SUPPLEMENT

### Outcomes Module

#### Primary Outcomes

**Description:** analysis method: 16s rRNA sequencing and bioinformatics analysis. Reported measure: taxonomic profiles of the microbial populations (operational taxonomic units / OTUs)

**Measure:** Fecal Microbiota

**Time Frame:** 12 weeks compared to baseline

**Description:** Acetate, propionate, isobutyrate, butyrate and isovalerate (μmol/L)

**Measure:** SCFA

**Time Frame:** 12 weeks compared to baseline

**Description:** Plasma LPS, adiponectin, leptin, resistin, IL-1, IL-6, IL-8, IL-10 and TNF-alpha concentrations (pg/mL)

**Measure:** Inflammatory parameters

**Time Frame:** 12 weeks compared to baseline

#### Secondary Outcomes

**Description:** μUI/mL

**Measure:** Fasting insulin

**Time Frame:** 12 weeks compared to baseline

**Description:** mg/dL

**Measure:** fasting blood glucose

**Time Frame:** 12 weeks compared to baseline

**Description:** HOMA-IR = \[fasting blood glucose (mmol) x fasting insulin (UI/ml)\] ÷ 22,5

**Measure:** HOMA-IR

**Time Frame:** 12 weeks compared to baseline

**Description:** percentage (%)

**Measure:** Glycated hemoglobin

**Time Frame:** 12 weeks compared to baseline

**Description:** µmol/L

**Measure:** Free Fat Acids

**Time Frame:** 12 weeks compared to baseline

**Description:** mg/dL.

**Measure:** Triglycerides

**Time Frame:** 12 weeks compared to baseline

**Description:** mg/dL

**Measure:** Total cholesterol

**Time Frame:** 12 weeks compared to baseline

**Description:** (Friedewald equation) LDL-c = total colesterol - HDL-c - Triglicerídeos/5

Reported measure: mg/dL

**Measure:** LDL-c

**Time Frame:** 12 weeks compared to baseline

**Description:** mg/dL

**Measure:** HDL-c

**Time Frame:** 12 weeks compared to baseline

**Description:** Dual X-ray Absorptiometry (DXA). Reported measure: T-score and Z-score

**Measure:** Bone densitometry

**Time Frame:** 12 weeks compared to baseline

**Description:** kilograms

**Measure:** Body weight (kg)

**Time Frame:** 12 weeks compared to baseline

**Description:** centimeters (cm)

**Measure:** Waist circumference (cm)

**Time Frame:** 12 weeks compared to baseline

**Description:** In metric units: BMI (kg/m²) = weight (kg) ÷ height² (meters). Reported measure: kg/m².

**Measure:** Body mass index (BMI)

**Time Frame:** 12 weeks compared to baseline

**Description:** Dual X-ray Absorptiometry (DXA). Reported measure: Total Body Fat Percentage (%BF)

**Measure:** Total Body Fat Percentage (%BF)

**Time Frame:** 12 weeks compared to baseline

**Description:** Dual X-ray Absorptiometry (DXA) - Fat Mass Index (FMI) - the total amount of fat (in kilograms) relative to the height (in meters²)

**Measure:** Fat Mass Index (FMI)

**Time Frame:** 12 weeks compared to baseline

**Description:** Dual X-ray Absorptiometry (DXA) - Total Body lean mass Percentage (%): The percent of the body that is not composed of fat.

**Measure:** Total Body lean mass Percentage (%)

**Time Frame:** 12 weeks compared to baseline

### Eligibility Module

**Eligibility Criteria:** 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

**Maximum Age:** 75 Years

**Minimum Age:** 35 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** erasmotrindade@gmail.com

**Name:** Erasmo Trindade, PhD

**Phone:** +55 48 3721-3489

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Florianópolis

**Contacts:**

***Contact 1:***

- **Email:** erasmotrindade@gmail.com

- **Name:** Erasmo BSM Trindade, PhD

- **Phone:** +55 48 3721-3489

- **Role:** CONTACT

**Country:** Brazil

**Facility:** Polydoro Ernani de São Thiago University Hospital

**State:** Santa Catarina

**Status:** RECRUITING

**Zip:** 88036-800

### IPD Sharing Statement Module

**IPD Sharing:** UNDECIDED

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000044882

- Term: Glucose Metabolism Disorders

- ID: D000008659

- Term: Metabolic Diseases

- ID: D000004700

- Term: Endocrine System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC18

- Name: Nutritional and Metabolic Diseases

- Abbrev: BC19

- Name: Gland and Hormone Related Diseases

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M7115

- Name: Diabetes Mellitus

- Relevance: HIGH

- As Found: Diabetes Mellitus

- ID: M7119

- Name: Diabetes Mellitus, Type 2

- Relevance: HIGH

- As Found: Type 2 Diabetes Mellitus

- ID: M11639

- Name: Metabolic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M25403

- Name: Glucose Metabolism Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M7862

- Name: Endocrine System Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000003920

- Term: Diabetes Mellitus

- ID: D000003924

- Term: Diabetes Mellitus, Type 2

### Intervention Browse Module - Browse Branches

- Abbrev: Infe

- Name: Anti-Infective Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Ot

- Name: Other Dietary Supplements

### Intervention Browse Module - Browse Leaves

- ID: M16201

- Name: Sulfalene

- Relevance: LOW

- As Found: Unknown

- ID: T367

- Name: Bifidobacterium

- Relevance: LOW

- As Found: Unknown

- ID: T355

- Name: Acidophilus

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-24
