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Mitochondrial Methylation in Type 2 Diabetes

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ClinicalTrials.gov Identifier: NCT04126551
Recruitment Status : Recruiting
First Posted : October 15, 2019
Last Update Posted : October 15, 2019
Sponsor:
Information provided by (Responsible Party):
Dawn K Coletta, University of Arizona

Tracking Information
First Submitted Date October 11, 2019
First Posted Date October 15, 2019
Last Update Posted Date October 15, 2019
Actual Study Start Date July 23, 2019
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: October 11, 2019)
Mitochondrial DNA methylation [ Time Frame: 3 years ]
Mitochondrial DNA methylation and D-loop of mitochondria is altered in insulin resistant states such as obesity and type 2 diabetes
Original Primary Outcome Measures Same as current
Change History No Changes Posted
Current Secondary Outcome Measures
 (submitted: October 11, 2019)
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
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Mitochondrial Methylation in Type 2 Diabetes
Official Title Unraveling the Role of Mitochondrial DNA Methylation in Type 2 Diabetes
Brief Summary 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 obesity and type 2 diabetes.
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 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, 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 Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
DNA will be extracted from vastus lateralis skeletal muscle biopsies and blood samples
Sampling Method Non-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
Condition
  • Obesity
  • Diabetes Mellitus, Type 2
  • Insulin Resistance
Intervention Other: Methylation status
Participants will be recruited, and muscle biopsies will be obtained for methylation analyses and measuring mitochondrial function
Study Groups/Cohorts
  • Lean, healthy control
    Lean, healthy control subjects. Volunteers will be matched for sex and age 35-55 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.
    Intervention: Other: Methylation status
  • Obese nondiabetic
    Obese nondiabetic subjects. Obesity will be defined using a body mass index of greater than or equal to 30 kg/m2. Volunteers will be matched for sex and age 35-55 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.
    Intervention: Other: Methylation status
  • Type 2 diabetes
    Participants with type 2 diabetes diagnosed accordingly to ADA criteria. Volunteers will be matched for sex and age 35-55 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.
    Intervention: Other: Methylation status
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: October 11, 2019)
36
Original Estimated Enrollment Same as current
Estimated Study Completion Date December 31, 2022
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  1. Subjects must be 35-55 years old
  2. Body Mass Index:

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

  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.
Sex/Gender
Sexes Eligible for Study: All
Ages 35 Years to 55 Years   (Adult)
Accepts Healthy Volunteers Not Provided
Contacts
Contact: Dawn K Coletta, PhD 520-626-9316 dcoletta@email.arizona.edu
Contact: Maria Gordon 520-626-5472 mgordon@email.arizona.edu
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT04126551
Other Study ID Numbers 1901254125
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Dawn K Coletta, University of Arizona
Study Sponsor University of Arizona
Collaborators Not Provided
Investigators
Principal Investigator: Dawn K Coletta, PhD University of Arizona
PRS Account University of Arizona
Verification Date October 2019