Molecular Regulation of Muscle Glucose Metabolism

Phase 1

Terminated

• Conditions: Obesity; Type 2 Diabetes Mellitus
• Interventions: Drug: U100 Humulin; Other: Exercise

• Registration Number: NCT01581736
• Lead Sponsor: Mayo Clinic

Brief Summary

This protocol is being conducted to determine the mechanisms responsible for insulin resistance, obesity and type 2 diabetes.

Detailed Description

This protocol involves performance of a hyperinsulinemic euglycemic clamp with 2 muscle biopsies and an exercise study with a muscle biopsy.

Study Timeline

• Study First Submitted: 2012-02-15
• Study Start: 2012-04
• Study First Submitted QC: 2012-04-18
• Study First Posted: 2012-04-20
• Primary Completion: 2016-04
• Study Completion: 2016-04
• Status Verified: 2017-11
• Last Update Submitted: 2017-11-22
• Last Update Posted: 2017-11-27

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 48

Inclusion Criteria

1. Subjects must be able to communicate meaningfully with the investigator and must be legally competent to provide written informed consent.

2. Subjects may be of either sex, age as described in each protocol. Female subjects must be non-lactating and must either be at least two years post-menopausal, (if diabetic or obese) or be using adequate contraceptive precautions (i.e. oral contraceptives, approved hormonal implant, intrauterine device, diaphragm with spermicide, condom with spermicide), or be surgically sterilized (i.e. bilateral tubal ligation, bilateral oophorectomy). Female patients (except for those patients who have undergone a hysterectomy or bilateral oophorectomy) are eligible only if they have a negative pregnancy test throughout the study period.

3. Subjects must range in age as described in each specific protocol.

4. All nondiabetic subjects must have normal oral glucose tolerance.

5. Subjects must have the following laboratory values:

   1. Hematocrit ≥ 35 vol%
   2. Serum creatinine ≤ 1.6 mg/dl
   3. Aspartate aminotransferase (AST) (SGOT) < 2 times upper limit of normal
   4. Alanine aminotransferase (ALT) (SGPT) < 2 times upper limit of normal
   5. Alkaline phosphatase < 2 times upper limit of normal
   6. Triglycerides < 150 mg/dl.
   7. Prothrombin time (PT) 11.7 -14.3 (During Liposyn/heparin infusion, PT will be determined to insure that it is < 1.5-2.0 times the normal value.)
   8. Partial thromboplastin time (PTT) 23.0-37.0.

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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 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.
2. 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.
3. 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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Exercise	U100 Humulin	Proteomics of muscle after a single bout of exercise compared to baseline with U100 Humulin infusion at rate of 80 milliunits(mU)/m\^2 surface area.
Exercise	Exercise	Proteomics of muscle after a single bout of exercise compared to baseline with U100 Humulin infusion at rate of 80 milliunits(mU)/m\^2 surface area.

Primary Outcome Measures

Name	Time	Method
insulin sensitivity	one month from date of volunteer study	euglycemic clamp

Secondary Outcome Measures

Name	Time	Method
acetylation of mitochondrial adenine nucleotide translocase	within 6 months of volunteer study	proteomics analysis of post translational modification of proteins obtained from isolated mitochondria

Trial Locations

Locations (1)

Mayo Clinic in Arizona; 🇺🇸 Scottsdale, Arizona, United States