DiabetesPGC-1NCT02282423
PGC-1 & Muscle Mitochondrial Dysfunction in Diabetes
A study testing Pre-study dietary and exercise instruction., Screening examination and oral glucose tolerance test and Euglycemic clamp in people with Diabetes and Obesity, run by Mayo Clinic at 1 site in United States.
Trial summary
The goal of this study is to understand how and why insulin resistant individuals respond differently to exercise as compared with insulin sensitive individuals at the skeletal muscle and gene expression level. Read more about this study
- Who is it for?
- Ages 30 to 59 yearsHealthy volunteers can take part
- What is being tested?
- Pre-study dietary and exercise instruction., Screening examination and oral glucose tolerance test and Euglycemic clamp
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- May 2014to Apr 2016
- Phase
- Interventional
- 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
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age 30-59
- BMI: Lean, BMI less than or equal to 25; Obese, BMI between 30-40; type 2 diabetic, BMI between 30-40.
- Subjects must be able to communicate meaningfully with the investigator and must be legally competent to provide written informed consent.
- Subjects may be of either sex with age as described in each protocol. Female subjects must be non-lactating and will be eligible only if they have a negative pregnancy test throughout the study period.
- Subjects must range in age as described in each specific protocol.
- Subjects must have the following laboratory values:
Show all 25Show 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 (except for Aim 4).
- Aim 4
- Age 30-59
- BMI: Lean, BMI less than or equal to 25; Obese, BMI between 30-40.
- Patients may have normal or impaired glucose tolerance.
- Subjects must be able to communicate meaningfully with the investigator and must be legally competent to provide written informed consent.
- Subjects may be of either sex with age as described in each protocol. Female subjects must be non-lactating and will be eligible only if they have a negative pregnancy test throughout the study period.
- 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 > 300 mg/dl for nondiabetics, > 250 mg/dl for impaired glucose tolerance.
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 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 metformin or thiazolidinediones, but may be taking sulfonylureas or other medications known to work through effects on insulin secretion.
- 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>180, diastolic BP>105, autonomic neuropathy, resting heart rate >100, electrolyte abnormalities.
Trial locations and contacts
1 site in 1 country.
About this study
The goal of this study is to understand how and why insulin resistant individuals respond differently to exercise as compared with insulin sensitive individuals at the skeletal muscle and gene expression level.
Read the detailed description
The goal of this study is to understand how and why insulin resistant individuals respond differently to exercise as compared with insulin sensitive individuals at the skeletal muscle and gene expression level. The study has four aims including testing if MZF1, NFKB1, RELA, SP1/KLF and EGRI expression responses are outside of the normal range in insulin resistant individuals and how insulin resistance changes the cell biosynthesis process/ post translational modifications. It also aims to define the response of MiRNAs in healthy and insulin resistant individuals and determine if treatment with Gemfibrozil inhibits transcription processes.
- Being tested
- Pre-study dietary and exercise instruction., Screening examination and oral glucose tolerance test, Euglycemic clamp, VO2max., Acute exercise bout
- Medical subject headings
- Diabetes Mellitus, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pre-study dietary and exercise instruction.Behavioural
All subjects will be instructed to continue their normal diet during the three days prior to study, to not consume alcohol the day before study, and to not engage in exercise for 48 hours before all studies.
Screening examination and oral glucose tolerance testProcedure or surgery
Also called OGTT
All subjects will have screening exam and OGTT at the Clinical Studies Infusion Unit at Mayo Clinic in Arizona at 7-8 am after having eaten nothing after 10 PM the night before, and have a screening examination and 75 g OGTT, as described
Euglycemic clampProcedure or surgery
On a separate day, subjects will have a two-hour euglycemic clamp ((80 mU insulin/(m2.min)) at the Clinical Studies Unit at Mayo Clinic Arizona at 7-8 am after an overnight fast. A muscle biopsy will be taken before the insulin infusion, to serve as the resting biopsy (3). Biopsy specimens (150-300 mg) will be frozen immediately in liquid nitrogen and stored in liquid nitrogen until they are processed
VO2max.Procedure or surgery
VO2max.
Acute exercise boutBehavioural
The single acute exercise bout will be performed as described (3). It consists of 4 sets of 12 min each (8 min @ 70% VO2max, 2 min @ 90%, 2 min rest, repeat X 4). Biopsies are taken 30 min and 24 hr after end of exercise. Resting biopsies are taken on the glucose clamp day
Percutaneous needle muscle biopsiesProcedure or surgery
Skeletal muscle biopsies, blotted free from blood, are frozen within 30 seconds in liquid nitrogen, and stored in liquid nitrogen until processing. We routinely obtain 150-300 mg muscle (wet weight), which is more than sufficient for the analyses proposed, with some muscle remaining for any additional validation assays that may arise during the course of the research. Muscle will be processed either for isolation of mRNA/microRNA or protein, as described (2, 3, 12).
| Study group | Role | What they receive |
|---|---|---|
| Lean Controls | Experimental | Lean controls will have BMI of 25 or less, gender specific normal body fat, and not be taking any medication that affects glucose metabolism.
Interventions include OGTT, Clamp, VO2 Max, Exercise Test and Muscle Biopsy Receives: Behavioral: Pre-study dietary and exercise instruction.; Procedure: Screening examination and oral glucose tolerance test; Procedure: Euglycemic clamp; Procedure: VO2max.; Behavioral: Acute exercise bout; Procedure: Percutaneous needle muscle biopsies |
| Obese, Non-diabetic | Experimental | Obese nondiabetics will have a BMI between 30-50 and not be taking any medication that affects glucose metabolism.
Interventions include OGTT, Clamp, VO2 Max, Exercise Test and Muscle Biopsy Receives: Behavioral: Pre-study dietary and exercise instruction.; Procedure: Screening examination and oral glucose tolerance test; Procedure: Euglycemic clamp; Procedure: VO2max.; Behavioral: Acute exercise bout; Procedure: Percutaneous needle muscle biopsies |
| Diabetic | Experimental | Diabetic patients will have a BMI between 30-50. We will recruit patients with mild or newly diagnosed type 2 diabetes who are treated with diet, sulfonylureas, or other drugs working through enhanced insulin secretion. Patients taking metformin or TZDs will not be recruited due to the effects of those drugs on insulin action.
Interventions include OGTT, Clamp, VO2 Max, Exercise Test and Muscle Biopsy Receives: Behavioral: Pre-study dietary and exercise instruction.; Procedure: Screening examination and oral glucose tolerance test; Procedure: Euglycemic clamp; Procedure: VO2max.; Behavioral: Acute exercise bout; Procedure: Percutaneous needle muscle biopsies |
| Non-diabetic | Experimental | Patients will be nondiabetic, although we will include patients with impaired glucose tolerance. Patients will meet criteria for treatment with fibrates to lower plasma triglyceride concentrations (triglyceride>300 mg/dl for nondiabetics, 250 mg/dl for patients with impaired glucose tolerance). We will aim at recruiting equal numbers of men and women. All participants will be between the ages of 30 and 59. Patients will have a BMI of 25-50 and not be taking any other medication that affects glucose metabolism. All participants will be sedentary (not reporting more than 10 minutes per day of light to vigorous leisure time physical activity.
Interventions include OGTT, Clamp, VO2 Max, Exercise Test and Muscle Biopsy Receives: Behavioral: Pre-study dietary and exercise instruction.; Procedure: Screening examination and oral glucose tolerance test; Procedure: Euglycemic clamp; Procedure: VO2max.; Behavioral: Acute exercise bout; Procedure: Percutaneous needle muscle biopsies |
What is being measured
The primary outcome is the main question the study is designed to answer.
Transcription Factor Response to Exercise
To determine whether expression of the transcription factor MZF1 is induced by exercise to a greater degree in control patients than in those with type 2 diabetes mellitus. MZF1 expression will be determined using quantitative rt-PCR analysis on RNA isolated from muscle biopsies taken from the patients. An repeated measures analysis of variance will be performed on the PCR data, for the three groups (lean, obese, type 2 diabetic), with the difference between the lean and diabetic groups being the primary measure. A P value of 0.05 will be considered significant.
Measured: 4-6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2014 (estimated)
- Study startMay 2014
- Primary completionApr 2016
- Study completionApr 2016
Why it stopped: PI job change
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DiabetesStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- Arizona State University
- Responsible party
- Principal investigator, Lawrence Mandarino, Mayo Clinic
- Investigators
- Lawrence J. Mandarino, Ph.D., Principal investigator, Mayo ClinicLori Roust, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02282423
- Sponsor's protocol ID
- 13-006411
- Acronym
- PGC-1
- Status last verified
- May 2016
- First submitted
- 29 Oct 2014
- Last updated
- 12 May 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PGC-1 & Muscle Mitochondrial Dysfunction in Diabetes
- ClinicalTrials.gov ID
- NCT02282423
- Acronym / sponsor ID
- PGC-1 / 13-006411
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: PI job change
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- Arizona State University
- Study start
- May 2014
- Primary completion
- Apr 2016 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 4 Nov 2014 (estimated)
- 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 goal of this study is to understand how and why insulin resistant individuals respond differently to exercise as compared with insulin sensitive individuals at the skeletal muscle and gene expression level.
Detailed description
The goal of this study is to understand how and why insulin resistant individuals respond differently to exercise as compared with insulin sensitive individuals at the skeletal muscle and gene expression level. The study has four aims including testing if MZF1, NFKB1, RELA, SP1/KLF and EGRI expression responses are outside of the normal range in insulin resistant individuals and how insulin resistance changes the cell biosynthesis process/ post translational modifications. It also aims to define the response of MiRNAs in healthy and insulin resistant individuals and determine if treatment with Gemfibrozil inhibits transcription processes.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Lean Controls | Experimental | Behavioral: Pre-study dietary and exercise instruction., Procedure: Screening examination and oral glucose tolerance test, Procedure: Euglycemic clamp, Procedure: VO2max., Behavioral: Acute exercise bout, Procedure: Percutaneous needle muscle biopsiesLean controls will have BMI of 25 or less, gender specific normal body fat, and not be taking any medication that affects glucose metabolism. Interventions include OGTT, Clamp, VO2 Max, Exercise Test and Muscle Biopsy |
| Obese, Non-diabetic | Experimental | Behavioral: Pre-study dietary and exercise instruction., Procedure: Screening examination and oral glucose tolerance test, Procedure: Euglycemic clamp, Procedure: VO2max., Behavioral: Acute exercise bout, Procedure: Percutaneous needle muscle biopsiesObese nondiabetics will have a BMI between 30-50 and not be taking any medication that affects glucose metabolism. Interventions include OGTT, Clamp, VO2 Max, Exercise Test and Muscle Biopsy |
| Diabetic | Experimental | Behavioral: Pre-study dietary and exercise instruction., Procedure: Screening examination and oral glucose tolerance test, Procedure: Euglycemic clamp, Procedure: VO2max., Behavioral: Acute exercise bout, Procedure: Percutaneous needle muscle biopsiesDiabetic patients will have a BMI between 30-50. We will recruit patients with mild or newly diagnosed type 2 diabetes who are treated with diet, sulfonylureas, or other drugs working through enhanced insulin secretion. Patients taking metformin or TZDs will not be recruited due to the effects of those drugs on insulin action. Interventions include OGTT, Clamp, VO2 Max, Exercise Test and Muscle Biopsy |
| Non-diabetic | Experimental | Behavioral: Pre-study dietary and exercise instruction., Procedure: Screening examination and oral glucose tolerance test, Procedure: Euglycemic clamp, Procedure: VO2max., Behavioral: Acute exercise bout, Procedure: Percutaneous needle muscle biopsiesPatients will be nondiabetic, although we will include patients with impaired glucose tolerance. Patients will meet criteria for treatment with fibrates to lower plasma triglyceride concentrations (triglyceride>300 mg/dl for nondiabetics, 250 mg/dl for patients with impaired glucose tolerance). We will aim at recruiting equal numbers of men and women. All participants will be between the ages of 30 and 59. Patients will have a BMI of 25-50 and not be taking any other medication that affects glucose metabolism. All participants will be sedentary (not reporting more than 10 minutes per day of light to vigorous leisure time physical activity. Interventions include OGTT, Clamp, VO2 Max, Exercise Test and Muscle Biopsy |
Who may qualify
- Ages
- 30 to 59 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (25 listed)
- Age 30-59
- BMI: Lean, BMI less than or equal to 25; Obese, BMI between 30-40; type 2 diabetic, BMI between 30-40.
- Subjects must be able to communicate meaningfully with the investigator and must be legally competent to provide written informed consent.
- Subjects may be of either sex with age as described in each protocol. Female subjects must be non-lactating and will be eligible only if they have a negative pregnancy test throughout the study period.
- Subjects must range in age as described in each specific protocol.
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 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 metformin or thiazolidinediones, but may be taking sulfonylureas or other medications known to work through effects on insulin secretion.
- 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>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.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pre-study dietary and exercise instruction.All subjects will be instructed to continue their normal diet during the three days prior to study, to not consume alcohol the day before study, and to not engage in exercise for 48 hours before all studies. | Behavioural | Diabetic, Lean Controls, Non-diabetic, Obese, Non-diabetic |
| Screening examination and oral glucose tolerance testAlso: OGTTAll subjects will have screening exam and OGTT at the Clinical Studies Infusion Unit at Mayo Clinic in Arizona at 7-8 am after having eaten nothing after 10 PM the night before, and have a screening examination and 75 g OGTT, as described | Procedure or surgery | Diabetic, Lean Controls, Non-diabetic, Obese, Non-diabetic |
| Euglycemic clampOn a separate day, subjects will have a two-hour euglycemic clamp ((80 mU insulin/(m2.min)) at the Clinical Studies Unit at Mayo Clinic Arizona at 7-8 am after an overnight fast. A muscle biopsy will be taken before the insulin infusion, to serve as the resting biopsy (3). Biopsy specimens (150-300 mg) will be frozen immediately in liquid nitrogen and stored in liquid nitrogen until they are processed | Procedure or surgery | Diabetic, Lean Controls, Non-diabetic, Obese, Non-diabetic |
| VO2max.VO2max. | Procedure or surgery | Diabetic, Lean Controls, Non-diabetic, Obese, Non-diabetic |
| Acute exercise boutThe single acute exercise bout will be performed as described (3). It consists of 4 sets of 12 min each (8 min @ 70% VO2max, 2 min @ 90%, 2 min rest, repeat X 4). Biopsies are taken 30 min and 24 hr after end of exercise. Resting biopsies are taken on the glucose clamp day | Behavioural | Diabetic, Lean Controls, Non-diabetic, Obese, Non-diabetic |
| Percutaneous needle muscle biopsiesSkeletal muscle biopsies, blotted free from blood, are frozen within 30 seconds in liquid nitrogen, and stored in liquid nitrogen until processing. We routinely obtain 150-300 mg muscle (wet weight), which is more than sufficient for the analyses proposed, with some muscle remaining for any additional validation assays that may arise during the course of the research. Muscle will be processed either for isolation of mRNA/microRNA or protein, as described (2, 3, 12). | Procedure or surgery | Diabetic, Lean Controls, Non-diabetic, Obese, Non-diabetic |
Primary outcome
Transcription Factor Response to Exercise
Time frame: 4-6 weeks
To determine whether expression of the transcription factor MZF1 is induced by exercise to a greater degree in control patients than in those with type 2 diabetes mellitus. MZF1 expression will be determined using quantitative rt-PCR analysis on RNA isolated from muscle biopsies taken from the patients. An repeated measures analysis of variance will be performed on the PCR data, for the three groups (lean, obese, type 2 diabetic), with the difference between the lean and diabetic groups being the primary measure. A P value of 0.05 will be considered significant.
Results and safety
The study was stopped early (reason given: PI job change). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2016.
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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 J. Mandarino, Ph.D. principal investigator
Mayo Clinic
Lori Roust, MD principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Pre-study dietary and exercise instruction., Screening examination and oral glucose tolerance test and Euglycemic clamp in people with Diabetes and Obesity, run by Mayo Clinic 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 25 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: stopped early, as of the sponsor's last update on 12 May 2016. 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 was stopped early (reason given: PI job change). Results are not available in the source record.
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?
Transcription Factor Response to Exercise (time frame: 4-6 weeks). 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 12 May 2016.