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Molecular Regulation of Muscle Glucose Metabolism

Primary Purpose

Obesity, Type 2 Diabetes Mellitus

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
U100 Humulin
Exercise
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Obesity focused on measuring insulin resistance, mitochondria

Eligibility Criteria

30 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

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.

Sites / Locations

  • Mayo Clinic in Arizona

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Exercise

Arm Description

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.

Outcomes

Primary Outcome Measures

insulin sensitivity
euglycemic clamp

Secondary Outcome Measures

acetylation of mitochondrial adenine nucleotide translocase
proteomics analysis of post translational modification of proteins obtained from isolated mitochondria

Full Information

First Posted
February 15, 2012
Last Updated
November 22, 2017
Sponsor
Mayo Clinic
Collaborators
Arizona State University
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1. Study Identification

Unique Protocol Identification Number
NCT01581736
Brief Title
Molecular Regulation of Muscle Glucose Metabolism
Official Title
Molecular Regulation of Muscle Glucose Metabolism
Study Type
Interventional

2. Study Status

Record Verification Date
November 2017
Overall Recruitment Status
Terminated
Why Stopped
PI job change
Study Start Date
April 2012 (undefined)
Primary Completion Date
April 2016 (Actual)
Study Completion Date
April 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mayo Clinic
Collaborators
Arizona State University

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obesity, Type 2 Diabetes Mellitus
Keywords
insulin resistance, mitochondria

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
48 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Exercise
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
U100 Humulin
Other Intervention Name(s)
Humulin, Human insulin
Intervention Description
Infused at a rate of 80/mU/m2 surface area per minute one time over 2 hours
Intervention Type
Other
Intervention Name(s)
Exercise
Intervention Description
Single episode of exercise riding a stationary bike.
Primary Outcome Measure Information:
Title
insulin sensitivity
Description
euglycemic clamp
Time Frame
one month from date of volunteer study
Secondary Outcome Measure Information:
Title
acetylation of mitochondrial adenine nucleotide translocase
Description
proteomics analysis of post translational modification of proteins obtained from isolated mitochondria
Time Frame
within 6 months of volunteer study

10. Eligibility

Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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, 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. Subjects must range in age as described in each specific protocol. All nondiabetic subjects must have normal oral glucose tolerance. Subjects must have the following laboratory values: Hematocrit ≥ 35 vol% Serum creatinine ≤ 1.6 mg/dl 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 (During Liposyn/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. Exclusion Criteria: 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. 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lori Roust, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Lawrence J. Mandarino, PhD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Arizona
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States

12. IPD Sharing Statement

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Molecular Regulation of Muscle Glucose Metabolism

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