NCT01726491

Brief Summary

The investigators are trying to understand the role of DNA (deoxyribonucleic acid) methylation in insulin resistance in skeletal muscle and blood tissues. DNA methylation is a normal chemical process in the body that modifies DNA. By studying this, the investigators hope to better understand the causes of insulin resistance.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
46

participants targeted

Target at P25-P50 for all trials

Timeline
Completed

Started Aug 2012

Longer than P75 for all trials

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 1, 2012

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

November 8, 2012

Completed
7 days until next milestone

First Posted

Study publicly available on registry

November 15, 2012

Completed
4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 21, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 21, 2016

Completed
Last Updated

January 16, 2018

Status Verified

January 1, 2018

Enrollment Period

4.3 years

First QC Date

November 8, 2012

Last Update Submit

January 11, 2018

Conditions

Diabetes Mellitus Type 2 in ObeseObesity

Keywords

Insulin resistanceExerciseType 2 diabetes mellitusObesityEpigenetic studies

Outcome Measures

Primary Outcomes (1)

  • DNA methylation of genes in insulin resistance

    DNA methylation of genes involved in mitochondrial biogenesis, oxidative phosphorylation, extracellular matrix and cytoskeleton proteins in insulin resistance, with an acute episode of exercise, and with eight weeks of training exercise.

    Baseline to visit 33 (approx 2 months)

Secondary Outcomes (1)

  • mRNA expression of genes

    Baseline to visit 33 approx 2 months

Study Arms (3)

Insulin resistance epigenetics

This experiment will use the Infinium methylation assay to perform epigenome mapping and define patterns of DNA methylation in skeletal muscle and whole blood tissue of metabolically well-characterized lean healthy, obese nondiabetic, and type 2 diabetic volunteers. We will test the hypotheses that (1) There is an increased methylation of genes involved in mitochondrial biogenesis and oxidative phosphorylation and altered methylation of promoters of genes coding for extracellular matrix and cytoskeletal proteins in insulin resistance, (2) The altered methylation patterns observed correspond to protein and mRNA expression changes, and (3) There are coordinated patterns of DNA methylation between the skeletal muscle and whole blood tissues in insulin resistance.

Single bout of exercise

This experiment will test the hypotheses in lean healthy, obese non-diabetic and type 2 diabetic volunteers that 1. Increased methylation of the PGC-1α promoter predicts a decreased response of this gene to a single bout of exercise, and 2. Altered methylation of promoters of nuclear encoded mitochondrial genes predicts a decreased response of this gene to a single bout of exercise.

Eight weeks of exercise

This experiment will test the hypothesis in lean healthy, obese non-diabetic and type 2 diabetic volunteers that 1. There is decreased methylation of genes involved in mitochondrial biogenesis and oxidative phosphorylation, and the altered methylation corresponds to protein and mRNA (messenger ribonucleic acid) expression changes, 2. There is altered methylation of genes involved in inflammation and cytoskeletal structure.

Eligibility Criteria

Age21 Years - 55 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)
Sampling MethodNon-Probability Sample
Study Population

Three groups of volunteers will be studied: 1) lean, healthy volunteers, 2)obese volunteers without type 2 diabetes, and 3) volunteers with type 2 diabetes.

Volunteers must be: * 21 - 55 years old * must be non-lactating, non-pregnant * not taking medications known to affect glucose or if taking them, on stable doses. * free of significant heart or lung disease

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

Study Sites (1)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

thigh muscle biopsies bloodsamples

MeSH Terms

Conditions

ObesityInsulin ResistanceMotor ActivityDiabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

OverweightOvernutritionNutrition DisordersNutritional and Metabolic DiseasesBody WeightSigns and SymptomsPathological Conditions, Signs and SymptomsHyperinsulinismGlucose Metabolism DisordersMetabolic DiseasesBehaviorDiabetes MellitusEndocrine System Diseases

Study Officials

  • Lori Roust, MD

    Mayo Clinic

    PRINCIPAL INVESTIGATOR

  • Dawn K Coletta, Ph.D.

    Mayo Clinic

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Consultant in Endocrinology

Study Record Dates

First Submitted

November 8, 2012

First Posted

November 15, 2012

Study Start

August 1, 2012

Primary Completion

November 21, 2016

Study Completion

November 21, 2016

Last Updated

January 16, 2018

Record last verified: 2018-01

Locations

US(1)