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

PreDiabetes Clinical Trial

— PRED2  

Official title:

Effect of the Genetic Variants Typical of the Mestizo Population That Confer Risk of Having Metabolic Diseases on the Response to Common Treatments (Diet, Physical Activity, Metformin, Exercise).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05990205
• Other study ID #: 2579
• Status: Completed
• Phase: Phase 2
• Start date: April 17, 2018
• Est. completion date: March 1, 2024

Study information

• Verified date: May 2023
• Source: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 437
• Est. completion date: March 1, 2024
• Est. primary completion date: December 20, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Glucose Intolerance
• PreDiabetes
• Prediabetic State

Intervention

Drug:
• 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

Behavioral:
• 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)

Locations

Country	Name	City	State
Mexico	Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán	Mexico City

Sponsors (1)

Lead Sponsor	Collaborator
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Country where clinical trial is conducted

Mexico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in weigth loss	Number of participants in each treatment arm reaching the the goal weight loss >3%	12 weeks
Secondary	Change in Total-Cholesterol parameters	Decreasing concentration of Total-Cholesterol (mg/dl)	12 weeks
Secondary	Change in LDL-Cholesterol parameters	Decreasing LDL-Cholesterol levels (mg/dl)	12 weeks
Secondary	Change in ApoB	Decreasing ApoB levels (mg/dl)	12 weeks
Secondary	Change in NonHDL-Cholesterol	Decreasin NonHDL-Cholesterol levels (mg/dl)	12 weeks
Secondary	Change in fasting glucose	Decreasing fasting glucose levels (mg/dl)	12 weeks
Secondary	Change in HbA1c	Decreasin HbA1c levels (%)	12 weeks