- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02116166
Skeletal Muscle Inflammation, Oxidative Stress and DNA Repair in Age-Related Sarcopenia
Claude D. Pepper Older Americans Independence Center (OAIC); Skeletal Muscle Inflammation, Oxidative Stress and DNA Repair in Age-Related Sarcopenia
Study Overview
Status
Conditions
Detailed Description
For this project, we will continue to gain mechanistic insight into age-related muscle loss and to maximize the utility of the tissue we previously collected (Claude D. Pepper Older Americans Independence Center (OAIC); Skeletal muscle apoptosis and physical performance; Oxidative RNA/DNA damage and repair in aged human muscle (Developmental Study), IRB # 429-2005) and we will collect muscle tissue from additional young subjects. This project will specifically test whether inflammatory pathways and DNA repair mechanisms are altered and/or involved in the development of sarcopenia and the related decline in physical function observed in the elderly.
Aim 1. We will further determine the association of skeletal muscle mass and function with intramuscular mediators of inflammation. Focus will be on inflammatory proteins (e.g.,TNF, TNFR1, pIkBα, pIKKb, CCL2, ZIP14, ZnT2) and genes (e.g., IL-6, TNFa, IL11β, IL-8, CCL2, CCR2, NFkB p50, NFkB p65, ZIP14) and metals (e.g., copper, zinc, and iron). We hypothesize that the majority of these markers will be upregulated in muscle from older individuals when compared to young.
Aim 2. For the first time, we will determine the age related effect of DNA damage on pattern and dynamics of mRNA translation in human muscle tissue by genome wide analysis using "ribosome profiling." The recently developed deep-sequencing techniques of RNA-seq and "ribosome profiling" will be implemented on human muscle. This will allow us to explore on a genomic scale and at single-nucleotide resolution, the effect of age-related DNA damage on transcriptional fidelity and translational kinetics. Importantly, for the first time, these phenotype changes will be compared with genome mapping of DNA damage, a major factor driving mammalian aging. We hypothesize that older muscle has greater modification of translational patterns compared to young muscle.
Muscle tissue samples remaining following the completion of this research will be stored and used in the future to explore new avenues of research related to aging.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
-
-
Florida
-
Gainesville, Florida, United States, 32611
- University of Florida
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- males and females aged 20-35.
- willing and able to give informed consent.
Exclusion Criteria:
- High physical activity level (i.e., the subject has spent greater than 300 minutes per week in the past 2 month performing structured physical activity, such as exercising at a gym and/or weight training)
- Active treatment for cancer or history of cancer in the past 3 years
- Congestive heart failure NYHA Class III or IV
- Previous stroke with upper and/or lower extremities involvement within the last 6 months
- Peripheral vascular disease Fontaine Class III/IV
- History of life-threatening cardiac arrhythmias, stroke, severe Parkinson's disease or severe neurological disorders likely to interfere with physical function
- Renal disease requiring dialysis
- Lung disease requiring steroids
- Lower extremity amputation
- Complicated diabetes
- Life-threatening illnesses with an estimated life expectancy less than 1 year
- Anticoagulant therapy (aspirin use is allowed, but participants will be asked to stop taking it 48 hours prior to muscle biopsy)
- Involved in active weight loss > 5 kg in prior 3 months
- Pregnancy (determined by a pregnancy test)
- Lidocaine allergy
Temporary exclusion criteria:
- Recent bacterial infection (< 2 weeks)
- Acute febrile illness in previous 2 months
- High blood pressure (i.e., BP ≥ 160/90 mm Hg) at the visit (subject will be referred to his/her physician and reevaluated after appropriated therapy being instituted)
- Taking aspirin within 48 hours preceding biopsy
- Performing exercise 48 hours prior to the biopsy.
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Cross-Sectional
Cohorts and Interventions
Group / Cohort |
---|
Young
Young (20-35 years old)
|
Old
Older (70-99 years old)
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Tumor Necrosis Factor alpha (TNF-alpha)
Time Frame: baseline
|
Inflammation marker; measured in muscle biopsy specimens.
|
baseline
|
tumor-necrosis factor receptor-1 (TNFR1)
Time Frame: baseline
|
Inflammation marker; measured in muscle biopsy specimens.
|
baseline
|
Phospho-Inhibitory Subunit Of NF-KBα (pIkBα)
Time Frame: baseline
|
Inflammation marker; measured in muscle biopsy specimens.
|
baseline
|
Chemokine (C-C motif) ligand 2 (CCL2)
Time Frame: baseline
|
Inflammation marker; measured in muscle biopsy specimens.
|
baseline
|
zinc transporter (ZIP) 14
Time Frame: baseline
|
Inflammation marker; measured in muscle biopsy specimens.
|
baseline
|
Interleukin 6 (IL-6)
Time Frame: baseline
|
Inflammation marker; measured in muscle biopsy specimens.
|
baseline
|
Interleukin (IL) 11β
Time Frame: baseline
|
Inflammation marker; measured in muscle biopsy specimens.
|
baseline
|
Interleukin 8 (IL-8)
Time Frame: baseline
|
Inflammation marker; measured in muscle biopsy specimens.
|
baseline
|
C-C chemokine receptor type 2 (CCR2)
Time Frame: baseline
|
Inflammation marker; measured in muscle biopsy specimens.
|
baseline
|
zinc transporter 14 (ZIP14)
Time Frame: baseline
|
Inflammation marker; measured in muscle biopsy specimens.
|
baseline
|
copper
Time Frame: baseline
|
metals; measured in muscle biopsy specimens.
|
baseline
|
zinc
Time Frame: baseline
|
metals; measured in muscle biopsy specimens.
|
baseline
|
iron
Time Frame: baseline
|
metals; measured in muscle biopsy specimens.
|
baseline
|
ribosome profiling
Time Frame: baseline
|
DNA damage on pattern and dynamics of mRNA translation in human muscle tissue; measured in muscle biopsy specimens.
|
baseline
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Christiaan Leeuwenburgh, PhD, University of Florida
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
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
- 201300790-N
- 2P30AG028740 (U.S. NIH Grant/Contract)
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.
Clinical Trials on Sarcopenia
-
University of Texas at AustinNot yet recruitingExercise Training and SarcopeniaUnited States
-
Centre Hospitalier Universitaire DijonCompleted
-
Creighton UniversityUniversity of NebraskaRecruiting
-
University Hospital, CaenCompleted
-
University of NottinghamUniversity of OxfordRecruitingMuscle Atrophy | Age-Related SarcopeniaUnited Kingdom
-
Tufts UniversityNational Institute on Aging (NIA)CompletedMuscle Loss | Age-Related SarcopeniaUnited States
-
China Medical University HospitalCompleted
-
King's College LondonCo-sponsor: Guy's and St Thomas' NHS Foundation TrustCompletedFrailty | Sarcopenia | Age-Related SarcopeniaUnited Kingdom
-
Norwegian School of Sport SciencesOslo University HospitalNot yet recruitingHealthy Aging | Testosterone Deficiency | Age-Related Sarcopenia
-
Ningbo Medical Center Lihuili HospitalCompletedHemodialysis Patients With SarcopeniaChina