Clinical Trials Logo

Clinical Trial Summary

This project uses both transcriptomic- and genomic-level data to identify mechanisms of individual responses to glucagon-like peptide-1 (GLP-1) in Mexican-Americans with prediabetes. The GLP-1 hormone is essential for glucose reduction, weight loss, cardiovascular risk reduction, and renal protection. Newly discovered mechanisms will illuminate causal links between disease genotype and phenotype, which may ultimately guide personalized therapeutic approaches for type 2 diabetes, prediabetes, obesity, cardiovascular disease, renal disease, and other related diseases.

Clinical Trial Description

This clinical trial will uncover new mechanisms of inter-individual responses to endogenous and exogenous glucagon-like peptide-1 (GLP-1) in Hispanics/Latinos (H/Ls) with prediabetes. The results move the management of prediabetes, type 2 diabetes mellitus (T2DM), and relevant metabolic diseases to a more individualized approach in an understudied and at-risk population. Few options exist for prediabetes treatment, and the current pharmaceutical management of T2DM does not predict drug treatment failures, nor differences in individual treatment responses and adverse effects. A precise, genetics-based approach will provide superior therapeutic management for patients. GLP-1-based therapies reduce blood glucose, promote weight loss, decrease cardiovascular events, and improve renal function. Prior genetic studies, most done in Caucasians, identified associations between genetic variants and decreased GLP-1-induced insulin secretion, in an effort to guide individualized treatment. However, these associations do not provide a clear mechanistic relationship between genotype and phenotype. Transcriptomic analyses will uncover many of these mechanisms. Here, we propose to 1) test the association of single nucleotide polymorphisms (SNPs) that regulate expression (eQTLs) of 11 candidate genes in a range of relevant metabolic tissues with differential GLP-1 response, 2) perform RNA sequencing before and after treatment to identify eQTLs in blood that predict response to GLP-1 therapy and develop risk-based prediction models in H/Ls, and 3) determine the effects of genetic regulation of candidate genes and newly discovered eQTLs phenome-wide in a large existing biobank, BioVU. For aims 1 and 2, responses will be measured in 300 study subjects with prediabetes recruited from an established Mexican-American cohort via the oral minimal model method, before and after GLP-1 therapy, quantifying GLP-1 hormone efficacy and GLP-1-induced pancreatic beta cell insulin release and peripheral insulin sensitivity. Procedures include serial measurements of plasma glucose, insulin, C-peptide, and GLP-1, and peripheral blood collection for RNA sequencing. Our central hypotheses are: (1) metabolic tissue-based eQTLs of GLP-1-associated genes will be associated with physiological response to endogenous and exogenous GLP-1,(2) identification of eQTLs associated with GLP-1 treatment-induced changes in whole blood will identify new gene targets, and (3) this data will lead to the creation of eQTL-based prediction models for related diseases. The study is innovative because it uses a novel combination of eQTL analysis and oral minimal model to assess GLP-1 response, examines a population highly underrepresented in pharmacogenomic studies, and utilizes novel statistical methods and applications to study gene expression. The significance of this newly acquired mechanistic information will ultimately guide precision therapeutic regimens for diabetes prevention and treatment, weight loss, cardiovascular risk reduction, and related metabolic complications in an understudied population. ;

Study Design

Related Conditions & MeSH terms

NCT number NCT05119179
Study type Interventional
Source The University of Texas Health Science Center, Houston
Contact Norma Perez-Olazaran
Phone (956) 755-0695
Email [email protected]
Status Recruiting
Phase Phase 4
Start date November 15, 2021
Completion date July 2026

See also
  Status Clinical Trial Phase
Completed NCT03644524 - Heat Therapy and Cardiometabolic Health in Obese Women N/A
Completed NCT03188263 - Morning Light Treatment to Improve Glucose Metabolism N/A
Recruiting NCT03821961 - 18F-FDOPA PET/CT Imaging in Patients Undergoing Metabolic Surgery N/A
Completed NCT04303468 - Intervention With a GABA Supplement in Prediabetics N/A
Active, not recruiting NCT03689608 - Daily vs Intermittent Restriction of Energy: Controlled Trial to Reduce Diabetes Risk (DIRECT) N/A
Recruiting NCT04527965 - Liver Fat as a Dietary Target for Treating Cardiometabolic Disorders in Prediabetes and Type 2 Diabetes N/A
Completed NCT03675360 - Low-Carbohydrate Dietary Pattern on Glycemic Outcomes Trial N/A
Recruiting NCT01910051 - Explorative Assessment of Biomarkers in Overweight and Obese Subjects
Completed NCT03527368 - The Time-Restricted Intake of Meals Study N/A
Not yet recruiting NCT04931836 - The Influence of Physical Activity on the Gut Microbiome of Pre-Diabetic Adults N/A
Completed NCT03865342 - Prevention of Diabetes Using Mobile-enabled, Virtual Delivery of the National Diabetes Prevention Program N/A
Completed NCT02899390 - Diabetes Prevention Program in Adults of the Yaqui Tribe of Hermosillo, Sonora at Risk of Diabetes N/A
Suspended NCT03240978 - Exercise Intervention for the Prevention of Prediabetes in Overweight Chinese N/A
Recruiting NCT01972113 - Vitamin K and Glucose Metabolism in Children at Risk for Diabetes (Vita-K 'n' Kids Study) N/A
Completed NCT01436916 - Oral Cholecalciferol in Prevention of Type 2 Diabetes Mellitus Phase 4
Completed NCT01432509 - Prospective Follow-up of a Cohort of Pre-diabetics in the North of France (DiabeNord) N/A
Completed NCT00990184 - Study to Evaluate the Effects of Colesevelam on Insulin Sensitivity and ß-Cell Function in Subjects With Impaired Fasting Glucose (Prediabetes) Phase 3
Completed NCT00886340 - A Lifestyle Change Program to Prevent Type 2 Diabetes Phase 2
Completed NCT04499287 - Mealtime Walking Study to Improve Postprandial Metabolic Response N/A
Not yet recruiting NCT04949958 - Effects of Exercise Based Manual in Sedentary Prediabetic Population N/A