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Insulin and Sarcopenia in the Elderly

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ClinicalTrials.gov Identifier: NCT00690534
Recruitment Status : Completed
First Posted : June 4, 2008
Last Update Posted : December 12, 2016
Sponsor:
Collaborator:
National Institute on Aging (NIA)
Information provided by (Responsible Party):
The University of Texas Medical Branch, Galveston

Study Description
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Brief Summary:
Muscle loss with aging is a significant contributor to disability in older people. Our general hypothesis is that loss of muscle with aging, known as sarcopenia, may be due to inability of muscle to grow in response to insulin. Our goal is to determine the mechanisms underlying this age-related insulin resistance of muscle proteins, which will allow us to define in the future specific interventions to target this defect and provide the scientific basis for the prevention and treatment of sarcopenia.

Condition or disease Intervention/treatment Phase
Sarcopenia Drug: Insulin Regular Drug: L-NMMA Drug: Sodium Nitroprusside Other: mixed meal Phase 1

Detailed Description:

Our general hypothesis is that a reduced response of muscle protein anabolism to insulin plays an important role in the loss of muscle mass with aging. Our goal is to determine the mechanisms underlying the age-related insulin resistance of muscle proteins, which will allow us to define specific interventions to target this defect and provide the scientific basis for the prevention and treatment of sarcopenia.

Our previous studies indicate that the response of muscle proteins to the anabolic action of insulin is impaired in healthy older adults as compared to younger controls, which hampers the anabolic effect of mixed feeding on muscle proteins. These changes are associated with an age-related reduction in the vasodilatory response to insulin, which, from our data, appears to be a potentially important mediator of the physiological anabolic effect of insulin on muscle proteins. Preliminary data from our laboratory also suggest that in older subjects a single bout of aerobic exercise may restore the normal response of blood flow, muscle protein synthesis and anabolism to insulin.

Therefore, we will test in healthy subjects the following specific hypotheses:

  1. Insulin-induced increases in blood flow and muscle perfusion are necessary for the physiological stimulation of muscle protein synthesis and anabolism by insulin.
  2. Aging reduces the vascular sensitivity to insulin, which prevents the physiological increase in blood flow and muscle perfusion in response to insulin, thereby decreasing the response of muscle protein synthesis and net balance to the anabolic action of insulin and mixed feeding.
  3. Aerobic exercise can restore, in older subjects, the insulin-induced increase in blood flow and muscle perfusion to youthful levels, thus normalizing the anabolic effect of insulin and mixed feeding on muscle protein synthesis and net muscle protein balance.

We will use state-of the art stable isotope tracer techniques to measure muscle protein turnover, and a newly developed method to measure muscle perfusion in young and older subjects. The results of these studies will allow us to better define the physiological mechanisms of action of insulin on muscle protein anabolism, advance our knowledge on the pathophysiology of sarcopenia, and provide the scientific basis for the behavioral and/or pharmacological treatment of muscle loss with aging.


Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 88 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Insulin and Sarcopenia in the Elderly
Study Start Date : September 2005
Actual Primary Completion Date : August 2012
Actual Study Completion Date : August 2012

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U.S. FDA Resources

Arms and Interventions
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Active Comparator: CMAY
Insulin in young
 Drug: Insulin Regular
insulin, 0.2 mU/kg/min for 3 hours
Experimental: IMAY
L-NMMA + insulin in young
 Drug: Insulin Regular
insulin, 0.2 mU/kg/min for 3 hours
Drug: L-NMMA
variable rate for 3 hours
Experimental: SNPY
SNP in young
 Drug: Sodium Nitroprusside
variable rate for 3 hours
Active Comparator: CSNP
Insulin in elderly
 Drug: Insulin Regular
insulin, 0.2 mU/kg/min for 3 hours
Experimental: ISNP
SNP in elderly
 Drug: Insulin Regular
insulin, 0.2 mU/kg/min for 3 hours
Drug: Sodium Nitroprusside
variable rate for 3 hours
Experimental: SNPE
SNP in elderly
 Drug: Sodium Nitroprusside
variable rate for 3 hours
Active Comparator: CMealO
Meal in elderly
 Other: mixed meal
mixed meal
Experimental: SMealO
SNP+meal in elderly
 Drug: Sodium Nitroprusside
variable rate for 3 hours
Other: mixed meal
mixed meal
Active Comparator: MealY
meal in young
 Other: mixed meal
mixed meal
Experimental: ExIns
insulin+exercise in elderly
 Drug: Insulin Regular
insulin, 0.2 mU/kg/min for 3 hours
Experimental: ExMeal
meal+exercise in elderly
 Other: mixed meal
mixed meal


Outcome Measures
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Primary Outcome Measures :
  1. muscle protein synthesis [ Time Frame: 5 and 8 hours ]

Secondary Outcome Measures :
  1. blood flow [ Time Frame: 5 and 8 hours ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Age 18-40 yrs, and 65-85 yrs.
  2. Ability to sign consent form (score >23 on the 30-item Mini Mental State Examination, MMSE)
  3. Stable body weight for at least 3 months

Exclusion Criteria:

  1. Physical dependence or frailty (impairment in any of the Activities of Daily Living (ADL), history of falls (>2/year) or significant weight loss in the past year)
  2. Exercise training (>2 weekly sessions of moderate to high intensity aerobic or resistance exercise)
  3. Pregnancy or nursing women.
  4. Significant heart, liver, kidney, blood or respiratory disease
  5. Peripheral vascular disease
  6. Diabetes mellitus or other untreated endocrine disease
  7. Active cancer
  8. Recent (within 6 months) treatment with anabolic steroids, or corticosteroids.
  9. Alcohol or drug abuse
  10. Severe depression (>5 on the 15-item Geriatric Depression Scale, GDS)
  11. Potential subjects who have recently donated blood in the past 60 days will be excluded from participating in the study.
Contacts and Locations
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00690534


Locations
United States, Texas
Sealy Center on Aging, University of Texas Medical Branch
Galveston, Texas, United States, 77555-0460
Sponsors and Collaborators
The University of Texas Medical Branch, Galveston
National Institute on Aging (NIA)
Investigators
Principal Investigator: Elena Volpi, MD, PhD The University of Texas Medical Branch at Galveston
More Information
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications of Results:

Responsible Party: The University of Texas Medical Branch, Galveston
ClinicalTrials.gov Identifier: NCT00690534     History of Changes
Other Study ID Numbers: 05-090
5R01AG018311 ( U.S. NIH Grant/Contract )
First Posted: June 4, 2008    Key Record Dates
Last Update Posted: December 12, 2016
Last Verified: January 2015
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No sharing. Drug was used off label for collection of measures for research project.

Keywords provided by The University of Texas Medical Branch, Galveston:
sarcopenia
aging
muscle metabolism

Additional relevant MeSH terms:
Sarcopenia
Muscular Atrophy
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Atrophy
Pathological Conditions, Anatomical
Signs and Symptoms
Insulin, Globin Zinc
 Insulin
Nitroprusside
Hypoglycemic Agents
Physiological Effects of Drugs
Antihypertensive Agents
Vasodilator Agents
Nitric Oxide Donors
Molecular Mechanisms of Pharmacological Action