Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Insulin and Sarcopenia in the Elderly

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

Tracking Information
First Submitted Date  ICMJE May 27, 2008
First Posted Date  ICMJE June 4, 2008
Last Update Posted Date December 12, 2016
Study Start Date  ICMJE September 2005
Actual Primary Completion Date August 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 30, 2008)
muscle protein synthesis [ Time Frame: 5 and 8 hours ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 30, 2008)
blood flow [ Time Frame: 5 and 8 hours ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Insulin and Sarcopenia in the Elderly
Official Title  ICMJE Insulin and Sarcopenia in the Elderly
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Sarcopenia
Intervention  ICMJE
  • Drug: Insulin Regular
    insulin, 0.2 mU/kg/min for 3 hours
  • Drug: L-NMMA
    variable rate for 3 hours
  • Drug: Sodium Nitroprusside
    variable rate for 3 hours
  • Other: mixed meal
    mixed meal
Study Arms  ICMJE
  • Active Comparator: CMAY
    Insulin in young
    Intervention: Drug: Insulin Regular
  • Experimental: IMAY
    L-NMMA + insulin in young
    Interventions:
    • Drug: Insulin Regular
    • Drug: L-NMMA
  • Experimental: SNPY
    SNP in young
    Intervention: Drug: Sodium Nitroprusside
  • Active Comparator: CSNP
    Insulin in elderly
    Intervention: Drug: Insulin Regular
  • Experimental: ISNP
    SNP in elderly
    Interventions:
    • Drug: Insulin Regular
    • Drug: Sodium Nitroprusside
  • Experimental: SNPE
    SNP in elderly
    Intervention: Drug: Sodium Nitroprusside
  • Active Comparator: CMealO
    Meal in elderly
    Intervention: Other: mixed meal
  • Experimental: SMealO
    SNP+meal in elderly
    Interventions:
    • Drug: Sodium Nitroprusside
    • Other: mixed meal
  • Active Comparator: MealY
    meal in young
    Intervention: Other: mixed meal
  • Experimental: ExIns
    insulin+exercise in elderly
    Intervention: Drug: Insulin Regular
  • Experimental: ExMeal
    meal+exercise in elderly
    Intervention: Other: mixed meal
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 30, 2008)
88
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE August 2012
Actual Primary Completion Date August 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00690534
Other Study ID Numbers  ICMJE 05-090
5R01AG018311 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: No sharing. Drug was used off label for collection of measures for research project.
Responsible Party The University of Texas Medical Branch, Galveston
Study Sponsor  ICMJE The University of Texas Medical Branch, Galveston
Collaborators  ICMJE National Institute on Aging (NIA)
Investigators  ICMJE
Principal Investigator: Elena Volpi, MD, PhD The University of Texas Medical Branch at Galveston
PRS Account The University of Texas Medical Branch, Galveston
Verification Date January 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP