Effect of the SCL16A11 Risk Haplotype on Treatments to Prevent Type 2 Diabetes

NCT ID: NCT05990205

Last Updated: 2024-05-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 437 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-04-17
• Study Completion Date: 2024-03-01

Brief Summary

The goal of this randomized clinical trial is to determine the impact of the risk haplotype on SLC16A11 on early therapeutic responses in treatments to prevent T2D in Mexican mestizos with prediabetes. The main question[s] it aims to answer are:

• Evaluate the effect of the risk haplotype on weigth loss >3%
• Evualuate the differences in lipid profiles and glycemic parameters (fasting glucose, HbA1c).

Participants will be randomized into two groups: lifestyle intervention (LSI): hypocaloric diet, 25 kcal/kg of ideal weight, 45% of the total intake of carbohydrates, 30% lipids, and 25% protein sources + physical activity (>150 min medium intensity per week), or LSI + MET (750 mg metformin twice a day).

Researchers will compare carriers and non carriers of the risk haplotype of SLC16A11 to see if there are diferent treatment responses.

Detailed Description

Objectives: Dietary modification and/or metformin remain the most cost-effective treatment to prevent type 2 diabetes (T2D). Yet, there is an important variation in receiving the benefit among individuals. A haplotype in SLC16A11 is associated with decreased insulin action and risk for T2D in Mexicans. We aim to determine the impact of the risk haplotype on SLC16A11 on early therapeutic responses in treatments to prevent T2D.

Methods: We recrute individuals with at least one prediabetes criteria according to the American Diabetes Association with a body mass index (BMI) between 25 and 45 kg/m2. Participants are randomized into two groups: lifestyle intervention (LSI): hypocaloric diet, 25 kcal/kg of ideal weight, 45% of the total intake of carbohydrates, 30% lipids, and 25% protein sources + physical activity (>150 min medium intensity per week), or LSI + MET (750 mg metformin twice a day). Standardized dietitians delivere the LSI. The treatment goal is to achieve >3% weight loss during the 12-week follow-up. Participants are genotyped for the risk allele rs13342232 and rs75493593. The effects of the risk haplotype are evaluated with linear and logistic regressions adjusted by age, sex, five genetic principal components, BMI, and prediabetes criteria at baseline. Primary outcome is a significant interaction between the treatment arm and genotype in weight loss goal >3% after the treatment. Secondary outcome are differences in lipid levels and third outcome is differences in glycemic parameters (fasting glucose, HbA1c).

Conditions

PreDiabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Life Style Intervention

Hypocaloric diet, 25 kcal/kg of ideal weight, 45% of the total intake of carbohydrates, 30% lipids, and 25% protein sources + physical activity (\>150 min medium intensity per week)

Group Type: ACTIVE_COMPARATOR

Life Style Intervention

Intervention Type: BEHAVIORAL

hypocaloric diet, 25 kcal/kg of ideal weight, 45% of the total intake of carbohydrates, 30% lipids, and 25% protein sources + physical activity (\>150 min medium intensity per week)

Life Style Intervention + Metformin

Hypocaloric diet, 25 kcal/kg of ideal weight, 45% of the total intake of carbohydrates, 30% lipids, and 25% protein sources + physical activity (\>150 min medium intensity per week) + (750 mg metformin twice a day).

Group Type: ACTIVE_COMPARATOR

Life Style Intervention + Metformin

Intervention Type: DRUG

hypocaloric diet, 25 kcal/kg of ideal weight, 45% of the total intake of carbohydrates, 30% lipids, and 25% protein sources + physical activity (\>150 min medium intensity per week) + Metformin extended release 750mg each 12 hours

Interventions

Life Style Intervention + Metformin

hypocaloric diet, 25 kcal/kg of ideal weight, 45% of the total intake of carbohydrates, 30% lipids, and 25% protein sources + physical activity (\>150 min medium intensity per week) + Metformin extended release 750mg each 12 hours

Intervention Type: DRUG

Life Style Intervention

hypocaloric diet, 25 kcal/kg of ideal weight, 45% of the total intake of carbohydrates, 30% lipids, and 25% protein sources + physical activity (\>150 min medium intensity per week)

Intervention Type: BEHAVIORAL

Other Intervention Names

LSI + MET; LSI

Eligibility Criteria

Inclusion Criteria

• Mexican mestizos
• At least one prediabetes criteria according to the American Diabetes Association: fasting glucose between 100-124 mg/dL, Glycosylated hemoglobin (HbA1c) between 5.7-6.4, and 2-hour blood sugar between 140 mg/dl-199 mg/dl after an oral load of 75g of glucose) (1);
• Age ranged between 18-65 years
• Overweight or obesity (BMI between 25.0 - 40 kg/m2).

Exclusion Criteria

• Chronic diseases
• Pregnancy
• Chronic use of medications that altered plasma glucose levels.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Carlos A Aguilar Salinas, PhD

Role: PRINCIPAL_INVESTIGATOR

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Locations

Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

Mexico City, , Mexico

Countries

Mexico

Other Identifiers

2579

Identifier Type: -

Identifier Source: org_study_id