Physical Inactivity and Insulin Resistance in Skeletal Muscle.

This study has been withdrawn prior to enrollment.
(protocol not approved by VA R&D)
Sponsor:
Collaborator:
Information provided by:
University of Missouri-Columbia
ClinicalTrials.gov Identifier:
NCT00536211
First received: September 25, 2007
Last updated: January 3, 2013
Last verified: January 2013
  Purpose

The purpose of this study is to determine how a decline in physical activity acutely leads to a decrease in insulin sensitivity in skeletal muscle. The hypothesis is that the loss of insulin sensitivity following physical inactivity is caused by a rapid reduction in skeletal muscle mitochondrial oxidative capacity.


Condition Intervention
Metabolic Syndrome X
Insulin Resistance
Hypertension
Hypercholesterolemia
Obesity
Behavioral: Exercise
Drug: Metformin

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Physical Inactivity and Insulin Resistance in Skeletal Muscle.

Resource links provided by NLM:


Further study details as provided by University of Missouri-Columbia:

Primary Outcome Measures:
  • Insulin sensitivity; following 12 weeks of exercise training and 1 and 3 days of detraining and + or - Metformin. [ Time Frame: 12 weeks and 3 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • PGC-1 alpha transcription and mitochondrial fatty acid oxidation and enzyme activity in skeletal muscle; following 12 weeks of exercise training and 1, 2, and 3 days of detraining and + or - Metformin. [ Time Frame: 12 weeks and 3 days ] [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: June 2009
Estimated Study Completion Date: December 2011
Estimated Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Exercise
Behavioral: Exercise
Exercise training will consist of walking and/or jogging on a treadmill 5 out of 7 d each week at ~60% of each subject's predetermined VO2max (75% maximal heart rate as monitored by heart rate monitors), 45 min/session, for 12 weeks. The exercise training will follow a three-stage progression: 1. wk 1 = 30 min, 3 d/wk, 60% VO2max; 2. wk 2 = 30 min, 5 d/wk, 60% VO2max; and 3. wk 3-12 = 45 min, 5 d/wk, 60% VO2max.
Active Comparator: 2
Metformin
Drug: Metformin
oral tablet, 1000 mg daily for 17 days

Detailed Description:

In this project we will study two diverse groups of subjects. Group 1 will be subjects who are sedentary, insulin resistant, and have the Metabolic Syndrome. These subjects will be tested for insulin sensitivity at the whole body level, and for key changes in skeletal muscle metabolism at baseline, following 12 weeks of exercise training, and during an acute (1-3 days) period of time following the cessation of exercise training. The design allows us to study the effects of exercise on improving insulin sensitivity and make direct comparisons to a period when insulin sensitivity quickly decreases because of the removal of exercise training. Metformin is a drug commonly prescribed to control insulin resistance and type 2 diabetes. Metformin is thought to have exercise like effects on muscle metabolism and is known to activate a molecule that is de-activated during inactivity. Thus, half of the Metabolic Syndrome subjects will cease exercise training with no treatment while another half will quite exercise training while taking the drug Metformin.

Group 2 subjects will be highly trained endurance athletes. Endurance athletes display high levels of insulin sensitivity that can drop in the hours and days following the cessation of exercise. Thus we will take the same measurements in endurance athletes at baseline during their normal training regimen and in the acute (1-3 days) period following the cessation of exercise training. Again, half of the subjects will be take Metformin during the cessation of exercise in the same fashion as done in group 1.

Studies in both groups seek to determine the event(s) which cause insulin resistance in skeletal muscle following a decrease in physical activity levels. Comparisons between healthy, active individuals and sedentary Metabolic Syndrome subjects may provide additional information about the underlying events that cause insulin resistance.

  Eligibility

Ages Eligible for Study:   20 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Selection of inclusion for Metabolic Syndrome Subjects :

Sedentary metabolic syndrome subjects will be 20-55 y of age, overweight to Class I or II obese (BMI 25-39 kg/m2) men and women, who have a fasting glucose of 100 to 125 mg/dl, and at least 2 of 4 other characteristics of the metabolic syndrome which are the following: waist circumference greater than 102 cm in men and 88 cm in women, serum triglyceride concentration greater than 150 mg/dl, HDL-C concentration greater than 40 mg/dl in men and 50 mg/dl in women, and blood pressure greater than 130/85 mmHG.

Selection for inclusion for Endurance Athlete Subjects:

Subjects who report training (running and/or biking) greater than 30 min a day, 4 days a week for at least 1 year will be included. Final inclusion criteria will be a VO2max of greater than 55 ml/kg/min.

To take part in the study, Women must currently be taking birth control or be postmenopausal.

Exclusion Criteria:

  • Subjects will be excluded from the study if they have or are:

Diagnosed cardiovascular disease or diabetes or disease symptoms that could alter their ability to perform exercise, fasting blood glucose of greater than 126 mg/dl, smokers, taking any medications or supplements (e.g., statins, fibrates, metformin, thiazolidinediones, anti-hypertensives (ACE-inhibitors and angiotensin blockers) which could affect blood lipids or insulin sensitivity.

Women who are pregnant or plan to become pregnant during the duration of the study For the Metabolic Syndrome subjects only individuals exercising regularly (more than one 30 min session per week) or have a physically active lifestyle (>8,000 daily steps as measured by a pedometer) will be excluded.

Individuals with an orthopedic limitations for walking. Allergies to drugs used in the study. Past or current liver and/or kidney problems of any nature.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00536211

Locations
United States, Missouri
Harry S. Truman Memorial Veterans' Hospital
Columbia, Missouri, United States, 65201
Sponsors and Collaborators
University of Missouri-Columbia
Investigators
Principal Investigator: John P Thyfault, PhD University of Missouri-Columbia
  More Information

Publications:

Responsible Party: John Thyfault, University of Missouri-Columbia
ClinicalTrials.gov Identifier: NCT00536211     History of Changes
Other Study ID Numbers: 1095378
Study First Received: September 25, 2007
Last Updated: January 3, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Missouri-Columbia:
Exercise
Physical Activity
Metformin
Hyperinsulinemic-Euglycemic Clamp
Muscle Biopsy
Fatty Acid Oxidation
Peroxisome proliferator-activated receptor gamma
Detraining
Inactivity
Skeletal muscle

Additional relevant MeSH terms:
Hypercholesterolemia
Hypertension
Insulin Resistance
Metabolic Syndrome X
Cardiovascular Diseases
Dyslipidemias
Glucose Metabolism Disorders
Hyperinsulinism
Hyperlipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Vascular Diseases
Metformin
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 22, 2014