Type2 DiabetesNCT03323788
PGC-1 & MUSCLE MITOCHONDRIAL DYSFUNCTION IN DIABETES: AIMS 1-4
An observational study of Type2 Diabetes and Obesity, run by University of Arizona at 1 site in United States.
Trial summary
We are trying to understand how insulin (a type of hormone in the body that regulates how the body regulates how one metabolizes protein and carbohydrates) and exercise alter proteins involved in energy production and metabolism in skeletal muscle. Read more about this study
- Who is it for?
- Ages 30 to 59 years
- Conditions the study is for
- Type2 Diabetes, Obesity
- How many people
- 96 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2016to 1 Aug 2018
- 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 30 to 59 years
- All sexes
- Adult
Study population: The plan is to have about 84 people take part in aims 1 to 3 and about 12 people in aim 4. Adults between the ages of 30 - 59 may participate.
Who may be able to join
None listed.
Who cannot join
- 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 may be taking a stable dose of estrogens or other hormonal replacement therapy, if the subject has been on these agents for the prior three months. Subjects taking systemic glucocorticoids are excluded. Patients with type 2 diabetes will be excluded if they are taking thiazolidinediones, but may be taking sulfonylureas or other medications known to work through effects on insulin sectretion.
- 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>180, diastolic BP>105, autonomic neuropathy, resting heart rate >100, electrolyte abnormalities.
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
The University of Arizona
Tucson, Arizona, 85724
Oscar Parra, MADM, 520-626-6485, oscardp@email.arizona.edu
Lawrence Mandarino, PhD
About this study
We are trying to understand how insulin (a type of hormone in the body that regulates how the body regulates how one metabolizes protein and carbohydrates) and exercise alter proteins involved in energy production and metabolism in skeletal muscle.
Read the detailed description
(Aims 1-3) We are trying to understand how insulin (a type of hormone in the body that regulates how the body regulates how one metabolizes protein and carbohydrates) and exercise alter proteins involved in energy production and metabolism in skeletal muscle. By studying this, they hope to better understand the causes of insulin resistance and Type 2 diabetes Insulin is a hormone that is produced normally in the body and causes blood sugar to return to normal after eating. Insulin resistance is a state when the body is not using insulin correctly, and more insulin is needed to keep blood sugar concentrations normal. Insulin resistance can lead to Type 2 diabetes. Type 2 diabetes is a disease in which blood sugar levels are too high. Our studies may help to find out why some people develop Type 2 diabetes and how exercise may prevent this disease.
(Aim 4) We are asking patients from aims 1-3 to take part in this research study because they have high triglycerides that could be treated anyway with fibrates, and they do not have diabetes.
Triglycerides and cholesterol are the two main kinds of fat that are in blood. People who have high triglycerides have some health risks and are sometimes treated with drugs called "fibrates". This drug turns on a protein in ones body that controls the activity of some of the genes that make it easier for their liver to get rid of triglycerides. We think that maybe this same gene, in ones muscle, can lower the ability of genes in ones muscle to respond beneficially to exercise, but we don't know if this is true.
- Conditions
- Type2 Diabetes, Obesity
- Medical subject headings
- Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Aim 1 | Aim 1. To determine whether the transcription factor expression response to exercise is dysregulated in muscle from type 2 diabetic patients. We will test the hypothesis that MZF1, NFKB1, RELA, SP1/KLF and EGR1 responses to an acute exercise bout are reduced in insulin resistant patients with type 2 diabetes. | |
| Aim 2 | Aim 2. To determine how insulin resistance changes the response of post-translational modifications of SP1/KLF family and MZF1 transcription factors to acute exercise in muscle from type 2 diabetic patients. We will test the hypothesis that: 1. SP1/KLF2, 4, and 6 and phosphorylation/acetylation and MZF1 phosphorylation is altered in response to acute exercise. 2. The response of SP1/KLF2, 4, and 6 phosphorylation and acetylation and MZF1 phosphorylation to acute exercise is abnormal in patients with type 2 diabetes. | |
| Aim 3 | Aim 3. To define the response of miRNAs to acute exercise in healthy and insulin resistant muscle from obese and type 2 diabetic patients. We will test the hypotheses that: 1. The exercise-induced increases in expression of miR-378 members and miR-128 are lower in obese and type 2 diabetic muscle than in lean healthy controls. 2. FOXO1 expression, a target of miR-378 and miR-128, is higher in obese and type 2 diabetic muscle and this is accompanied by decreased FOXO1 phosphorylation. 3. The exercise-induced increases in expression of miR-30 family members, miR-10a, miR-422a, and miR-532 are lower in obese and type 2 diabetic muscle. 4. There are novel miRNAs that regulate the transcriptional program induced by acute exercise and are dysregulated in insulin resistance. | |
| Aim 4 | Aim 4. To determine whether treatment with PPAR-Alpha agonist fibrate derivatives suppresses the normal gene expression response to acute exercise. We will test the hypothesis that Gemfibrozil treatment inhibits the normal transcriptional response to exercise. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response of muscle mRNA to acute exercise
mRNA differential response in muscle to exercise in obese patients
Measured: 2014-2019
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2017
- Study startNov 2016
- Primary completion1 Aug 2018 (estimated)
- Study completion1 Aug 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type2 DiabetesStudies 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
- 96 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Arizona
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lawrence Mandarino, University of Arizona
- Investigators
- Lawrence Mandarino, PHD, Principal investigator, The University of Arizona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03323788
- Sponsor's protocol ID
- 1606632517
- Status last verified
- Oct 2017
- First submitted
- 24 Oct 2017
- Last updated
- 27 Oct 2017
- Results posted
- 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 27 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PGC-1 & MUSCLE MITOCHONDRIAL DYSFUNCTION IN DIABETES: AIMS 1-4
- ClinicalTrials.gov ID
- NCT03323788
- Acronym / sponsor ID
- 1606632517
- Conditions
- Type2 Diabetes, Obesity
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 96 participants (estimated)
- Lead sponsor
- University of ArizonaUniversity, hospital or other
- Study start
- Nov 2016 (actual)
- Primary completion
- 1 Aug 2018 (estimated)
- Study completion
- 1 Aug 2018 (estimated)
- First posted
- 27 Oct 2017 (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.
We are trying to understand how insulin (a type of hormone in the body that regulates how the body regulates how one metabolizes protein and carbohydrates) and exercise alter proteins involved in energy production and metabolism in skeletal muscle.
Detailed description
(Aims 1-3) We are trying to understand how insulin (a type of hormone in the body that regulates how the body regulates how one metabolizes protein and carbohydrates) and exercise alter proteins involved in energy production and metabolism in skeletal muscle. By studying this, they hope to better understand the causes of insulin resistance and Type 2 diabetes Insulin is a hormone that is produced normally in the body and causes blood sugar to return to normal after eating. Insulin resistance is a state when the body is not using insulin correctly, and more insulin is needed to keep blood sugar concentrations normal. Insulin resistance can lead to Type 2 diabetes. Type 2 diabetes is a disease in which blood sugar levels are too high. Our studies may help to find out why some people develop Type 2 diabetes and how exercise may prevent this disease.
(Aim 4) We are asking patients from aims 1-3 to take part in this research study because they have high triglycerides that could be treated anyway with fibrates, and they do not have diabetes.
Triglycerides and cholesterol are the two main kinds of fat that are in blood. People who have high triglycerides have some health risks and are sometimes treated with drugs called "fibrates". This drug turns on a protein in ones body that controls the activity of some of the genes that make it easier for their liver to get rid of triglycerides. We think that maybe this same gene, in ones muscle, can lower the ability of genes in ones muscle to respond beneficially to exercise, but we don't know if this is true.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Aim 1 | – | –Aim 1. To determine whether the transcription factor expression response to exercise is dysregulated in muscle from type 2 diabetic patients. We will test the hypothesis that MZF1, NFKB1, RELA, SP1/KLF and EGR1 responses to an acute exercise bout are reduced in insulin resistant patients with type 2 diabetes. |
| Aim 2 | – | –Aim 2. To determine how insulin resistance changes the response of post-translational modifications of SP1/KLF family and MZF1 transcription factors to acute exercise in muscle from type 2 diabetic patients. We will test the hypothesis that: 1. SP1/KLF2, 4, and 6 and phosphorylation/acetylation and MZF1 phosphorylation is altered in response to acute exercise. 2. The response of SP1/KLF2, 4, and 6 phosphorylation and acetylation and MZF1 phosphorylation to acute exercise is abnormal in patients with type 2 diabetes. |
| Aim 3 | – | –Aim 3. To define the response of miRNAs to acute exercise in healthy and insulin resistant muscle from obese and type 2 diabetic patients. We will test the hypotheses that: 1. The exercise-induced increases in expression of miR-378 members and miR-128 are lower in obese and type 2 diabetic muscle than in lean healthy controls. 2. FOXO1 expression, a target of miR-378 and miR-128, is higher in obese and type 2 diabetic muscle and this is accompanied by decreased FOXO1 phosphorylation. 3. The exercise-induced increases in expression of miR-30 family members, miR-10a, miR-422a, and miR-532 are lower in obese and type 2 diabetic muscle. 4. There are novel miRNAs that regulate the transcriptional program induced by acute exercise and are dysregulated in insulin resistance. |
| Aim 4 | – | –Aim 4. To determine whether treatment with PPAR-Alpha agonist fibrate derivatives suppresses the normal gene expression response to acute exercise. We will test the hypothesis that Gemfibrozil treatment inhibits the normal transcriptional response to exercise. |
Who may qualify
- Ages
- 30 to 59 years
- Sex
- All
- Age groups
- Adult
- Study population
- The plan is to have about 84 people take part in aims 1 to 3 and about 12 people in aim 4. Adults between the ages of 30 - 59 may participate.
Key inclusion criteria (0 listed)
Key exclusion criteria (3 listed)
- 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 may be taking a stable dose of estrogens or other hormonal replacement therapy, if the subject has been on these agents for the prior three months. Subjects taking systemic glucocorticoids are excluded. Patients with type 2 diabetes will be excluded if they are taking thiazolidinediones, but may be taking sulfonylureas or other medications known to work through effects on insulin sectretion.
- 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>180, diastolic BP>105, 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.
Primary outcome
Response of muscle mRNA to acute exercise
Time frame: 2014-2019
mRNA differential response in muscle to exercise in obese patients
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2017.
- 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.
Lawrence Mandarino, PHD principal investigator
The 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 Type2 Diabetes 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 0 inclusion and 3 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: status not confirmed, as of the sponsor's last update on 27 Oct 2017. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Oscar D Parra, MADM (520-626-6485, oscardp@email.arizona.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response of muscle mRNA to acute exercise (time frame: 2014-2019). 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 27 Oct 2017.