Insulin and Sarcopenia in the Elderly

December 8, 2016 updated by: The University of Texas Medical Branch, Galveston
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

88

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Galveston, Texas, United States, 77555-0460
        • Sealy Center on Aging, University of Texas Medical Branch

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 81 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
muscle protein synthesis
Time Frame: 5 and 8 hours
5 and 8 hours

Secondary Outcome Measures

Outcome Measure
Time Frame
blood flow
Time Frame: 5 and 8 hours
5 and 8 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The University of Texas Medical Branch, Galveston

Collaborators

National Institute on Aging (NIA)

Investigators

  • Principal Investigator: Elena Volpi, MD, PhD, The University of Texas Medical Branch at Galveston

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2005

Primary Completion (Actual)

August 1, 2012

Study Completion (Actual)

August 1, 2012

Study Registration Dates

First Submitted

May 27, 2008

First Submitted That Met QC Criteria

May 30, 2008

First Posted (Estimate)

June 4, 2008

Study Record Updates

Last Update Posted (Estimate)

December 12, 2016

Last Update Submitted That Met QC Criteria

December 8, 2016

Last Verified

January 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 05-090
  • 5R01AG018311 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

No sharing. Drug was used off label for collection of measures for research project.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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