NCT00536211

Brief Summary

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.

Trial Health

30
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Timeline
Completed

Started Jun 2009

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 25, 2007

Completed
2 days until next milestone

First Posted

Study publicly available on registry

September 27, 2007

Completed
1.7 years until next milestone

Study Start

First participant enrolled

June 1, 2009

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2011

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2011

Completed
Last Updated

May 4, 2021

Status Verified

August 1, 2015

Enrollment Period

2.3 years

First QC Date

September 25, 2007

Last Update Submit

April 29, 2021

Conditions

Metabolic Syndrome XInsulin ResistanceHypertensionHypercholesterolemiaObesity

Keywords

ExercisePhysical ActivityMetforminHyperinsulinemic-Euglycemic ClampMuscle BiopsyFatty Acid OxidationPeroxisome proliferator-activated receptor gammaDetrainingInactivitySkeletal muscle

Outcome Measures

Primary Outcomes (1)

  • Insulin sensitivity; following 12 weeks of exercise training and 1 and 3 days of detraining and + or - Metformin.

    12 weeks and 3 days

Secondary Outcomes (1)

  • 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.

    12 weeks and 3 days

Study Arms (2)

1

EXPERIMENTAL

Exercise

Behavioral: Exercise

2

ACTIVE COMPARATOR

Metformin

Drug: Metformin

Interventions

ExerciseBEHAVIORAL

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.

1
MetforminDRUG

oral tablet, 1000 mg daily for 17 days

2

Eligibility Criteria

Age20 Years - 55 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Harry S. Truman Memorial Veterans' Hospital

Columbia, Missouri, 65201, United States

Location

Related Publications (6)

  • Shulman GI. Cellular mechanisms of insulin resistance. J Clin Invest. 2000 Jul;106(2):171-6. doi: 10.1172/JCI10583. No abstract available.

    PMID: 10903330BACKGROUND

  • Haapanen N, Miilunpalo S, Pasanen M, Oja P, Vuori I. Agreement between questionnaire data and medical records of chronic diseases in middle-aged and elderly Finnish men and women. Am J Epidemiol. 1997 Apr 15;145(8):762-9. doi: 10.1093/aje/145.8.762.

    PMID: 9126003BACKGROUND

  • Koves TR, Li P, An J, Akimoto T, Slentz D, Ilkayeva O, Dohm GL, Yan Z, Newgard CB, Muoio DM. Peroxisome proliferator-activated receptor-gamma co-activator 1alpha-mediated metabolic remodeling of skeletal myocytes mimics exercise training and reverses lipid-induced mitochondrial inefficiency. J Biol Chem. 2005 Sep 30;280(39):33588-98. doi: 10.1074/jbc.M507621200. Epub 2005 Aug 3.

    PMID: 16079133BACKGROUND

  • Russell AP, Feilchenfeldt J, Schreiber S, Praz M, Crettenand A, Gobelet C, Meier CA, Bell DR, Kralli A, Giacobino JP, Deriaz O. Endurance training in humans leads to fiber type-specific increases in levels of peroxisome proliferator-activated receptor-gamma coactivator-1 and peroxisome proliferator-activated receptor-alpha in skeletal muscle. Diabetes. 2003 Dec;52(12):2874-81. doi: 10.2337/diabetes.52.12.2874.

    PMID: 14633846BACKGROUND

  • Suwa M, Egashira T, Nakano H, Sasaki H, Kumagai S. Metformin increases the PGC-1alpha protein and oxidative enzyme activities possibly via AMPK phosphorylation in skeletal muscle in vivo. J Appl Physiol (1985). 2006 Dec;101(6):1685-92. doi: 10.1152/japplphysiol.00255.2006. Epub 2006 Aug 10.

    PMID: 16902066BACKGROUND

  • Kawate R, Yamakido M, Nishimoto Y, Bennett PH, Hamman RF, Knowler WC. Diabetes mellitus and its vascular complications in Japanese migrants on the Island of Hawaii. Diabetes Care. 1979 Mar-Apr;2(2):161-70. doi: 10.2337/diacare.2.2.161.

    PMID: 520120BACKGROUND

MeSH Terms

Conditions

Metabolic SyndromeInsulin ResistanceHypertensionHypercholesterolemiaObesityMotor ActivitySedentary Behavior

Interventions

ExerciseMetformin

Condition Hierarchy (Ancestors)

HyperinsulinismGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesVascular DiseasesCardiovascular DiseasesHyperlipidemiasDyslipidemiasLipid Metabolism DisordersOverweightOvernutritionNutrition DisordersBody WeightSigns and SymptomsPathological Conditions, Signs and SymptomsBehavior

Intervention Hierarchy (Ancestors)

Motor ActivityMovementMusculoskeletal Physiological PhenomenaMusculoskeletal and Neural Physiological PhenomenaBiguanidesGuanidinesAmidinesOrganic Chemicals

Study Officials

  • John P Thyfault, PhD

    University of Missouri-Columbia

    PRINCIPAL INVESTIGATOR
0

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 25, 2007

First Posted

September 27, 2007

Study Start

June 1, 2009

Primary Completion

October 1, 2011

Study Completion

December 1, 2011

Last Updated

May 4, 2021

Record last verified: 2015-08

Locations

US(1)