OverweightNCT04126551
Mitochondrial Methylation in Type 2 Diabetes
An observational study of Overweight and Obesity, run by University of Arizona at 1 site in United States.
Trial 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 overweight/obesity and type 2 diabetes. Read more about this study
- Who is it for?
- Ages 21 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Overweight, Obesity, Diabetes Mellitus, Type 2
- What is being tested?
- Methylation status
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Jul 2019to 31 Dec 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
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
Who may be able to join
- Subjects must be 21-55 years old
- 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)
- Subjects must be able to communicate meaningfully with the investigator and must be legally competent to provide written informed consent.
- 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)
- Subjects must have the following laboratory values:
Show all 15Show fewer
- 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
Who cannot join
- 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.
- Subjects receiving Gemfibrozil must not also be receiving a statin.
- 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.
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Clinical and Translational Research Center (CaTS)
Tucson, Arizona, 85724
About this study
Official title: 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.
Read the 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).
- Conditions
- Overweight, Obesity, Diabetes Mellitus, Type 2, Insulin Resistance
- Being tested
- Methylation status
- Medical subject headings
- Overweight, Obesity, Diabetes Mellitus, Type 2, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Methylation statusOther
Participants will be recruited, and muscle biopsies will be obtained for methylation analyses and measuring mitochondrial function
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: Methylation status | |
| 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. Receives: Other: Methylation status | |
| 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. Receives: Other: Methylation status |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mitochondrial DNA methylation
Mitochondrial DNA methylation and D-loop of mitochondria is altered in insulin resistant states such as overweight/obesity and type 2 diabetes
Measured: 3 years
Secondary outcomes (1)
Mitochondrial Function
The extent of mitochondrial function impairment in insulin resistant participants corresponds to the degree of methylation of the mitochondrial genome and D-loop
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2019
- Study start23 Jul 2019
- Primary completion31 Dec 2023
- Study completion31 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for OverweightStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Arizona
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dawn K Coletta, University of Arizona
- Investigators
- Dawn K Coletta, PhD, Principal investigator, University of Arizona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04126551
- Sponsor's protocol ID
- 1901254125
- Status last verified
- May 2024
- First submitted
- 11 Oct 2019
- Last updated
- 7 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Unraveling the Role of Mitochondrial DNA Methylation in Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT04126551
- Acronym / sponsor ID
- 1901254125
- Conditions
- Overweight, Obesity, Diabetes Mellitus, Type 2, Insulin Resistance
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- University of ArizonaUniversity, hospital or other
- Study start
- 23 Jul 2019 (actual)
- Primary completion
- 31 Dec 2023 (actual)
- Study completion
- 31 Dec 2023 (actual)
- First posted
- 15 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Lean, healthy control | – | Other: Methylation statusLean, 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. |
| Overweight/obese nondiabetic | – | Other: Methylation statusOverweight/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. |
| Type 2 diabetes | – | Other: Methylation statusParticipants 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. |
Who may qualify
- Ages
- 21 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- 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
Key inclusion criteria (15 listed)
- Subjects must be 21-55 years old
- 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)
- Subjects must be able to communicate meaningfully with the investigator and must be legally competent to provide written informed consent.
- 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)
Key exclusion criteria (4 listed)
- 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.
- Subjects receiving Gemfibrozil must not also be receiving a statin.
- 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.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Methylation statusParticipants will be recruited, and muscle biopsies will be obtained for methylation analyses and measuring mitochondrial function | Other | Lean, healthy control, Overweight/obese nondiabetic, Type 2 diabetes |
Primary outcome
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
1 secondary outcome
Mitochondrial Function
Time frame: 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dawn K Coletta, PhD principal investigator
University of Arizona
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Overweight and Obesity, run by University of Arizona at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mitochondrial DNA methylation (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2024; AzTrials last refreshed its copy on 29 Oct 2026.