DiabetesNCT01724515
PGC-1 and Mitochondrial Dysfunction in Diabetes
A study testing Lipid infusion and muscle biopsies in people with Diabetes and Obese, run by Mayo Clinic at 1 site in United States.
Trial summary
The purpose of this study is determine if you have too much fat in your body that it will decrease the conversion of food energy into energy that your body can use. Read more about this study
- Who is it for?
- Ages 21 to 55 yearsHealthy volunteers can take part
- What is being tested?
- Lipid infusion and muscle biopsies
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2012to Mar 2014
- 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 21 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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:
- Hematocrit ≥ 35 vol%
- Serum creatinine ≤ 1.6 mg/dl
Show all 12Show fewer
- Aspartate Aminotransferase (AST) (SGOT) < 2 times upper limit of normal
- Alanine Aminotransferase (ALT) (SGPT) < 2 times upper limit of normal
- Alkaline phosphatase < 2 times upper limit of normal
- Triglycerides < 150 mg/dl.
- Prothrombin Time (PT) 11.7 - 14.3 seconds (during Intralipid/heparin infusion, PT will be determined to insure that it is < 1.5-2.0 times the normal value.)
- Partial Thromboplastin Time (PTT) 23.0-37.0 seconds.
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.
- 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 purpose of this study is determine if you have too much fat in your body that it will decrease the conversion of food energy into energy that your body can use.
Read the detailed description
The investigators' prior research has focused on defining the changes in expression of nuclear encoded mitochondrial genes that predict changes in insulin sensitivity in skeletal muscle, with the goal of defining the molecular mechanisms underlying the connection between mitochondrial dysfunction and insulin resistance in skeletal muscle.
The purpose of this study is to determine whether experimental lipid oversupply decreases mitochondrial respiratory function. We will use mitochondrial respiration studies in vitro and mass spectrometry and proteomics analysis to test the hypothesis that experimental lipid oversupply:
- Decreases mitochondrial respiration in response to lipid fuels.
- Reduces abundance of mitochondrial proteins.
- Alters phosphorylation of proteins in the electron transport chain.
Three groups of subjects will be studied: lean, healthy control subjects (n=12), obese non-diabetic subjects (n=12) and patients with type 2 Diabetes Mellitus (n=12) for a total of 36 subjects. Twenty subjects have completed the study at Arizona State University; the remaining 16 subjects will be accrued at the Mayo Clinic in Arizona.
Subjects will come to the Mayo Clinic 2 times. On study Day 1 subjects will be screened with a medical history and physical exam, and a 75 g oral glucose tolerance test, measure body fat percentage, and an electrocardiogram (EKG). On Study Day 2, subjects will report to the clinic after an overnight fast. Female subjects will take a urine pregnancy test. A muscle biopsy will be performed to take a small sample from one thigh. A lipid infusion will be performed for 5 hours (60 ml/hr), with blood samples taken at 8 intervals during the infusion. At the end of the 5 hour period, a second muscle biopsy will be taken from the other thigh. The fat infusion will stop, subjects will be given lunch and allowed to leave the clinic.
- Being tested
- Lipid infusion and muscle biopsies
- Keywords
- insulin resistance
- Medical subject headings
- Diabetes Mellitus, Obesity, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lipid infusion and muscle biopsiesOther
Subjects will undergo a baseline muscle biopsy, a lipid infusion for 5 hours (60 ml/hr), and a muscle biopsy after the lipid infusion.
| Study group | Role | What they receive |
|---|---|---|
| Obese Non-Diabetic Subjects | Experimental | All subjects on this arm will undergo lipid infusion and muscle biopsies. Receives: Other: Lipid infusion and muscle biopsies |
| Type 2 Diabetic Subjects | Experimental | All subjects on this arm will undergo lipid infusion and muscle biopsies. Receives: Other: Lipid infusion and muscle biopsies |
| Healthy Control Subjects | Experimental | All subjects on this arm will undergo lipid infusion and muscle biopsies. Receives: Other: Lipid infusion and muscle biopsies |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mitochondrial Respiration
Mitochondrial respiration will be measured by micropolarography.
Measured: Study Day 2, muscle biopsy approximately 6 hours after lipid infusion initiation
Secondary outcomes (2)
Protein Concentration of Mitochondria
Protein concentration will be determined by the method of Lowry. 75 micrograms of muscle lysate proteins will be separated on a 10% Sodium Dodecyl Sulfate Polyacrylamide Gel, and then visualized with Coomassie stain. The gel lane will be cut into cubes, digested with trypsin and cleaned, then protein abundance will be determined using spectral counting.
Measured: Study Day 2, muscle biopsy approximately 6 hours after lipid infusion initiation
Phosphorylation of proteins
Phosphopeptides will be measured by mass spectrometry.
Measured: Study Day 2, muscle biopsy approximately 6 hours after lipid infusion initiation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2012 (estimated)
- Study startSep 2012
- Primary completionMar 2014
- Study completionMar 2014
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
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lawrence Mandarino, Mayo Clinic
- Investigators
- Lawrence Mandarino, Ph.D, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01724515
- Sponsor's protocol ID
- 11-006065 Aim 5
- Other IDs
- R01DK066483
- Status last verified
- May 2014
- First submitted
- 7 Nov 2012
- Last updated
- 12 May 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PGC-1 and Mitochondrial Dysfunction in Diabetes
- ClinicalTrials.gov ID
- NCT01724515
- Acronym / sponsor ID
- 11-006065 Aim 5
- Keywords
- insulin resistance
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- Sep 2012
- Primary completion
- Mar 2014 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 9 Nov 2012 (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 purpose of this study is determine if you have too much fat in your body that it will decrease the conversion of food energy into energy that your body can use.
Detailed description
The investigators' prior research has focused on defining the changes in expression of nuclear encoded mitochondrial genes that predict changes in insulin sensitivity in skeletal muscle, with the goal of defining the molecular mechanisms underlying the connection between mitochondrial dysfunction and insulin resistance in skeletal muscle.
The purpose of this study is to determine whether experimental lipid oversupply decreases mitochondrial respiratory function. We will use mitochondrial respiration studies in vitro and mass spectrometry and proteomics analysis to test the hypothesis that experimental lipid oversupply:
- Decreases mitochondrial respiration in response to lipid fuels.
- Reduces abundance of mitochondrial proteins.
- Alters phosphorylation of proteins in the electron transport chain.
Three groups of subjects will be studied: lean, healthy control subjects (n=12), obese non-diabetic subjects (n=12) and patients with type 2 Diabetes Mellitus (n=12) for a total of 36 subjects. Twenty subjects have completed the study at Arizona State University; the remaining 16 subjects will be accrued at the Mayo Clinic in Arizona.
Subjects will come to the Mayo Clinic 2 times. On study Day 1 subjects will be screened with a medical history and physical exam, and a 75 g oral glucose tolerance test, measure body fat percentage, and an electrocardiogram (EKG). On Study Day 2, subjects will report to the clinic after an overnight fast. Female subjects will take a urine pregnancy test. A muscle biopsy will be performed to take a small sample from one thigh. A lipid infusion will be performed for 5 hours (60 ml/hr), with blood samples taken at 8 intervals during the infusion. At the end of the 5 hour period, a second muscle biopsy will be taken from the other thigh. The fat infusion will stop, subjects will be given lunch and allowed to leave the clinic.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Obese Non-Diabetic Subjects | Experimental | Other: Lipid infusion and muscle biopsiesAll subjects on this arm will undergo lipid infusion and muscle biopsies. |
| Type 2 Diabetic Subjects | Experimental | Other: Lipid infusion and muscle biopsiesAll subjects on this arm will undergo lipid infusion and muscle biopsies. |
| Healthy Control Subjects | Experimental | Other: Lipid infusion and muscle biopsiesAll subjects on this arm will undergo lipid infusion and muscle biopsies. |
Who may qualify
- Ages
- 21 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- 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:
Key exclusion criteria (3 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.
- 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 |
|---|---|---|
| Lipid infusion and muscle biopsiesSubjects will undergo a baseline muscle biopsy, a lipid infusion for 5 hours (60 ml/hr), and a muscle biopsy after the lipid infusion. | Other | Healthy Control Subjects, Obese Non-Diabetic Subjects, Type 2 Diabetic Subjects |
Primary outcome
Mitochondrial Respiration
Time frame: Study Day 2, muscle biopsy approximately 6 hours after lipid infusion initiation
Mitochondrial respiration will be measured by micropolarography.
2 secondary outcomes
Protein Concentration of Mitochondria
Time frame: Study Day 2, muscle biopsy approximately 6 hours after lipid infusion initiation
Phosphorylation of proteins
Time frame: Study Day 2, muscle biopsy approximately 6 hours after lipid infusion initiation
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 12 May 2014.
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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, Ph.D 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 Lipid infusion and muscle biopsies in people with Diabetes and Obese, 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 12 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: finished, as of the sponsor's last update on 12 May 2014. 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 Respiration (time frame: Study Day 2, muscle biopsy approximately 6 hours after lipid infusion initiation). 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 2014.