Metabolic Syndrome XNCT00536211
Physical Inactivity and Insulin Resistance in Skeletal Muscle.
A study testing Exercise and Metformin in people with Metabolic Syndrome X and Insulin Resistance, run by University of Kansas Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Metabolic Syndrome X, Insulin Resistance, Hypertension
- What is being tested?
- Exercise and Metformin
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2009to Dec 2011
- 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 20 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Harry S. Truman Memorial Veterans' Hospital
Columbia, Missouri, 65201
About this study
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.
Read the 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.
- Being tested
- Exercise, Metformin
- Keywords
- Exercise, Physical Activity, Metformin, Hyperinsulinemic-Euglycemic Clamp, Muscle Biopsy, Fatty Acid Oxidation, Peroxisome proliferator-activated receptor gamma, Detraining, Inactivity, Skeletal muscle
- Medical subject headings
- Metabolic Syndrome, Insulin Resistance, Hypertension, Hypercholesterolemia, Obesity, Motor Activity, Sedentary Behavior
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ExerciseBehavioural
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.
MetforminDrug
oral tablet, 1000 mg daily for 17 days
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Exercise Receives: Behavioral: Exercise |
| 2 | Active comparator | Metformin Receives: Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Insulin sensitivity; following 12 weeks of exercise training and 1 and 3 days of detraining and + or - Metformin.
Measured: 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.
Measured: 12 weeks and 3 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Sep 2007 (estimated)
- Study startJun 2009
- Primary completionOct 2011 (estimated)
- Study completionDec 2011 (estimated)
Why it stopped: protocol not approved by VA R\&D
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Metabolic Syndrome XStudies of the same condition, open and under way.
- More trials run by University of Kansas Medical CenterThe 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Kansas Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- US Department of Veterans Affairs
- Responsible party
- Sponsor
- Investigators
- John P Thyfault, PhD, Principal investigator, University of Missouri-Columbia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00536211
- Sponsor's protocol ID
- 1095378
- Status last verified
- Aug 2015
- First submitted
- 25 Sep 2007
- Last updated
- 4 May 2021
- Results posted
- No
- Data monitoring committee
- No
Publications
Shulman GI. Cellular mechanisms of insulin resistance. J Clin Invest. 2000 Jul;106(2):171-6. doi: 10.1172/JCI10583. No abstract available.
PubMed 10903330Haapanen 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.
PubMed 9126003Koves 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.
PubMed 16079133Russell 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.
PubMed 14633846Suwa 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.
PubMed 16902066Kawate 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.
PubMed 520120
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Physical Inactivity and Insulin Resistance in Skeletal Muscle.
- ClinicalTrials.gov ID
- NCT00536211
- Acronym / sponsor ID
- 1095378
- Keywords
- Exercise, Physical Activity, Metformin, Hyperinsulinemic-Euglycemic Clamp, Muscle Biopsy, Fatty Acid Oxidation, Peroxisome proliferator-activated receptor gamma, Detraining
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: protocol not approved by VA R\&D
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of Kansas Medical CenterUniversity, hospital or other
- Collaborators
- US Department of Veterans Affairs
- Study start
- Jun 2009
- Primary completion
- Oct 2011 (estimated)
- Study completion
- Dec 2011 (estimated)
- First posted
- 27 Sep 2007 (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 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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Behavioral: ExerciseExercise |
| 2 | Active comparator | Drug: MetforminMetformin |
Who may qualify
- Ages
- 20 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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.
- 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.
Key exclusion criteria (4 listed)
- 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.
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 |
|---|---|---|
| ExerciseExercise 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. | Behavioural | 1 |
| Metforminoral tablet, 1000 mg daily for 17 days | Drug | 2 |
Primary outcome
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
1 secondary outcome
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
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2021.
- Background: PubMed 10903330Shulman GI. Cellular mechanisms of insulin resistance. J Clin Invest. 2000 Jul;106(2):171-6. doi: 10.1172/JCI10583. No abstract available.
- Background: PubMed 9126003Haapanen 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.
- Background: PubMed 16079133Koves 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.
- Background: PubMed 14633846Russell 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.
- Background: PubMed 16902066Suwa 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.
- Background: PubMed 520120Kawate 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.
Related trials for Metabolic Syndrome X
Not yet recruitingPhase 2
Effects of Meal Macronutrients on Postprandial Lipids
Nephrotic Syndrome, Lipodystrophy
RecruitingObservational study
Longitudinal Study of Ultra-rare Inherited Metabolic and Degenerative Neurological Diseases.
Inherited Disease, Rare Diseases
RecruitingObservational study
Cancer in Inherited Bone Marrow Failure Syndromes
Diamond Blackfan Anemia, Dyskeratosis Congenita
RecruitingPhase 1/2
The Effect of SGLT2 Inhibition on Adipose Inflammation and Endothelial Function
Obesity, Metabolic Syndrome
Enrolling by invitationEarly Phase 1
Truway Diagnostic Tools in Primary Care
Chronic Disease, Type 2 Diabetes Mellitus (T2DM), Obesity, Overweight
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.
John P Thyfault, PhD principal investigator
University of Missouri-Columbia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Exercise and Metformin in people with Metabolic Syndrome X and Insulin Resistance, run by University of Kansas Medical Center 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 5 inclusion and 4 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: withdrawn, as of the sponsor's last update on 4 May 2021. 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 was withdrawn before enrolling participants, so there are no results.
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?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00536211, which also lists 6 linked publications.
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 4 May 2021.