Mitochondrial Methylation in Type 2 Diabetes

May 4, 2024 updated by: Dawn K Coletta, University of Arizona

Unraveling the Role of Mitochondrial DNA Methylation in Type 2 Diabetes

The overarching goal of this proposal is to determine whether DNA methylation of the mitochondrial DNA impairs mitochondrial function in insulin resistant states such as overweight/obesity and type 2 diabetes.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

To determine whether differences in human skeletal muscle DNA methylation patterns in the mitochondrial and nuclear genome can explain the lower abundance of ETC and OXPHOS mRNA and protein observed in insulin resistant skeletal muscle of overweight/obese and type 2 diabetic participants. To determine whether patterns of human skeletal muscle DNA methylation in the mitochondrial and nuclear genome are predictive of ETC function. We will isolate skeletal muscle mitochondria from metabolically well-characterized lean insulin sensitive, overweight/obese insulin resistant nondiabetic and obese insulin resistant type 2 diabetic volunteers, and functionally evaluate each ETC complex (I - IV) and complex V (ATP synthase).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
27

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Arizona
      • Tucson, Arizona, United States, 85724
        • Clinical and Translational Research Center (CaTS)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

21 years to 55 years (Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

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

Description

Inclusion Criteria:

  1. Subjects must be 21-55 years old

  2. Body Mass Index:

    Lean, healthy BMI ≤25; Overweight,non-diabetic BMI 25-29.9; Obese, non-diabetic BMI 30-50; Type 2 Diabetes (per the American Diabetes Association criteria)

  3. Subjects must be able to communicate meaningfully with the investigator and must be legally competent to provide written informed consent.
  4. Female subjects must be non-lactating and will be eligible only if they have a negative pregnancy test throughout the study period, and must agree to use acceptable birth control (hormonal contraceptives, barrier methods, have an intrauterine device, or surgical sterilization)

  5. Subjects must have the following laboratory values:

    • Hematocrit ≥ 35 vol%
    • Serum creatinine ≤ 1.6 mg/dl
    • AST (SGOT) < 2 times upper limit of normal
    • ALT (SGPT) < 2 times upper limit of normal
    • Alkaline phosphatase < 2 times upper limit of normal
    • Triglycerides < 150 mg/dl for nondiabetics
    • Triglycerides <300 for diabetics
    • INR ≤ 1.3
    • HbA1c ≤ 10

Exclusion Criteria:

  1. Subjects must not be receiving any of the following medications: thiazide or furosemide diuretics, beta-blockers, or other chronic medications with known adverse effects on glucose tolerance levels unless the patient has been on a stable dose of such agents for the past three months before entry into the study. Subjects must not be taking estrogens or other hormonal replacement therapy unless the subject has been on these agents on a stable dose for the prior three months. Subjects taking systemic glucocorticoids are excluded. Patients with type 2 diabetes will be excluded if they are taking thiazolidinediones.
  2. Subjects receiving Gemfibrozil must not also be receiving a statin.
  3. Subjects with a history of clinically significant heart disease (New York Heart Classification greater than grade II; more than non-specific ST-T wave changes on the EKG), peripheral vascular disease (history of claudication), or pulmonary disease (dyspnea on exertion of one flight or less; abnormal breath sounds on auscultation) will not be studied.
  4. Recent systemic or pulmonary embolus, untreated high-risk proliferative retinopathy, recent retinal hemorrhage, uncontrolled hypertension, systolic BP>160, diastolic BP>95, autonomic neuropathy, resting heart rate >100, electrolyte abnormalities.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Lean, healthy control
Lean, healthy control subjects. Volunteers will be matched for sex and age 21-55 years old. Ethnicities studied will be self-reported. We will attempt to match on race/ethnicities with equal numbers of non-Hispanic/Latinos and Hispanics/Latinos.
Other: Methylation status
Participants will be recruited, and muscle biopsies will be obtained for methylation analyses and measuring mitochondrial function
Overweight/obese nondiabetic
Overweight/Obese nondiabetic subjects. Overweight and obesity will be defined using the standard body mass index cutoffs. Volunteers will be matched for sex and age 21-55 years old. Ethnicities studied will be self-reported. We will attempt to match on race/ethnicities with equal numbers of non-Hispanic/Latinos and Hispanics/Latinos.
Other: Methylation status
Participants will be recruited, and muscle biopsies will be obtained for methylation analyses and measuring mitochondrial function
Type 2 diabetes
Participants with type 2 diabetes will be diagnosed accordingly to ADA criteria. Volunteers will be matched for sex and age 21-55 years old. Ethnicities studied will be self-reported. We will attempt to match on race/ethnicities with equal numbers of non-Hispanic/Latinos and Hispanics/Latinos.
Other: Methylation status
Participants will be recruited, and muscle biopsies will be obtained for methylation analyses and measuring mitochondrial function

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Mitochondrial DNA methylation
Time Frame: 3 years
Mitochondrial DNA methylation and D-loop of mitochondria is altered in insulin resistant states such as overweight/obesity and type 2 diabetes
3 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Mitochondrial Function
Time Frame: 3 years
The extent of mitochondrial function impairment in insulin resistant participants corresponds to the degree of methylation of the mitochondrial genome and D-loop
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Arizona

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Dawn K Coletta, PhD, University of Arizona

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 23, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 11, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 11, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 15, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 7, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 4, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 1901254125

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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