- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02638454
Role of MicroRNAs on Age and Contraction-induced Skeletal Muscle Growth
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The age-associated loss of skeletal muscle mass and function (sarcopenia) is associated with substantial social and economic costs. The plasticity and adaptability of skeletal muscle to contraction (ie. resistance-exercise) is a fundamental physiological event leading to larger and more robust skeletal muscle. However, muscle growth in response to resistance exercise (RE), like other anabolic stimuli, is attenuated in older adults. The cause of aberrant muscle adaptation with aging is complex. Recent work has revealed a novel role for small non-coding RNAs, called microRNAs (miRNA) in the regulation of gene expression. Using an integrated bioinformatics analysis of protein-coding gene and miRNA array data from young and older men, I identified ten specific miRNAs as important regulators of muscle plasticity (Plasticity Related miRs [PR-miRs]) leading to the transcriptional response to exercise and lean mass in young and older men. However, the precise mechanisms underlying the expression of PR-miRs on age-related changes in muscle anabolism and sarcopenia are currently unknown.
Thus, the overall objective of this K01 application will be to determine the mechanistic role(s) of these PR-miRs in skeletal muscle adaptation to anabolic stimulation in:
- healthy young,
- sarcopenic older and
- age- and functionally-matched non-sarcopenic older males and females.
This will be accomplished by determine the differences in expression of PR-miRs with aging and sarcopenia in response to anabolic stimulation (AIM 1). Mechanistically determine the extent to which manipulation of PR-miR levels in vitro, in human primary myocytes, can reverse anabolic resistance observed with age and sarcopenia (AIM 2) and the effect of altering PR-miRs levels on skeletal muscle growth and development (AIM 3). This project will improve our understanding of the molecular mechanisms that contribute to the loss of skeletal muscle and eventually leading to the development of drug therapies for the treatment of sarcopenia in the ever growing aging population.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Massachusetts
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Boston, Massachusetts, United States, 02111
- Human Nutrition Research Center on Aging at Tufts University
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Male and Female
- 20-30 or 70-85 years of age
- Sedentary: Must not participate in any regular exercise sessions (participants who walk regularly or walk for exercise are eligible)
- Individuals must confirm good health
- BMI must be between 19-35 kg/m2
- Individuals must be fluent in English
- Willing to come to the HNRCA laboratory for study visits
- Short Physical Performance Battery of less than 9 (70-85 years of age cohort)
- 10 subjects with Normal Muscle Mass and 10 subjects with Low Muscle Mass as determined by DXA scan (70-85 years of age cohort) Low Muscle Mass is defined as Class I Sarcopenia, Skeletal Muscle Index within 1 to 2 standard deviations from the sex-specific mean of young adults
Exclusion Criteria:
- Lost or gained 7.5% or more of their body weight in the past 6 months
- Acute or terminal disease
- Significant immune disorder
- Types I and II Diabetes mellitus
- Uncontrolled hypertension (>180/100 mmHg)
- Neuromuscular disease
- Subjects must also not be participating in any regular endurance or resistance training exercise during the previous six months.
- Mini-mental state examination (MMSE) score of <23
- Because of the DXA scan and the unknown risk associated with the muscle biopsy procedure, women who are pregnant, planning to become pregnant, or are breastfeeding will be excluded from the study.
Subjects with a history of any of the following within the past 6 months will be excluded:
- Myocardial infarction in the past 6 months, or other symptomatic coronary artery disease.
- Surgery in previous 6 months
- Upper or lower extremity fracture in the previous 6 months
- Allergy to lidocaine
Subjects currently taking any of the following drugs or classes of drugs will be excluded:
- Anticoagulant therapy (Warfarin, Coumadin, or Plavix)
- ACE inhibitors
- Drugs that affects neuromuscular function
- Angiotensin receptor blockers
- Androgen or estrogen therapy or other hormone replacement therapy
- Low dose aspirin with known cardiovascular disease (e.g.: reported coronary artery disease, peripheral vascular disease, or previous stroke, or history of transient ischemic attacks)
- Diabetes medications (ie. metformin, insulin therapy, thiazolidinediones, sulfonylureas etc.)
- Chronic corticosteroid therapy
Laboratory blood test exclusions:
- Estimated GFR <30 mL/min/1.73m2
- Other abnormal screening lab values will be at the discretion of the study physician
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: HL-YNG
Healthy young sedentary males and females 20-30 yrs old Participants will undergo an acute bout of resistance exercise at 80% of their 1 repetition maximum (1RM, maximum strength) and will undergo muscle biopsies before, immediately after and 4 hours after the exercise. |
1 bout of high-intensity resistance exercise at 80% of the individuals 1 repetition maximum
Other Names:
|
Experimental: FL-OLD
Functionally-limited older sedentary males and females without sarcopenia (70-85 yrs old) Participants will undergo an acute bout of resistance exercise at 80% of their 1 repetition maximum (1RM, maximum strength) and will undergo muscle biopsies before, immediately after and 4 hours after the exercise. |
1 bout of high-intensity resistance exercise at 80% of the individuals 1 repetition maximum
Other Names:
|
Experimental: SR-OLD
Functionally-limited older sedentary males and females with clinically defined sarcopenia (70-85 yrs old) Participants will undergo an acute bout of resistance exercise at 80% of their 1 repetition maximum (1RM, maximum strength) and will undergo muscle biopsies before, immediately after and 4 hours after the exercise. |
1 bout of high-intensity resistance exercise at 80% of the individuals 1 repetition maximum
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change of microRNA expression in humans skeletal muscle after an acute bout of high intensity resistance exercise
Time Frame: Baseline, immediately (within 15-30 min after acute resistance exercise) and 4 hours after acute resistance exercise
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Determine if the expression of miRNA in skeletal muscle after an acute bout of high-intensity resistance exercise in young, functionally-limited older adults with and without low muscle mass
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Baseline, immediately (within 15-30 min after acute resistance exercise) and 4 hours after acute resistance exercise
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Donato A Rivas, PhD, Tufts University
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2860
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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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