Study of Muscle Repair Following Exercise in Young and Elderly People

Healthy Clinical Trial

— MDS  

Official title:

Exploring the Metabolic and Molecular Basis of Age-related Declines in Human Skeletal Muscle Regenerative Capacity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02174692
• Other study ID #: MDS
• Status: Completed
• Phase: N/A
• First received: June 11, 2014
• Last updated: May 28, 2015
• Start date: February 2013
• Est. completion date: March 2015

Study information

• Verified date: May 2015
• Source: University of Nottingham
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: University of Nottingham Research Ethics Committee
• Study type: Interventional

Clinical Trial Summary

The aim of this study is to understand how healthy muscle repairs in response to eccentric exercise by evaluating functional, metabolic and molecular measures. Furthermore, this study will aim to understand the repair mechanisms in elderly healthy muscle following eccentric exercise by evaluating the same measures and highlighting age-related differences in repair mechanisms which may account for the age-related loss in muscle mass. It is hypothesised that elderly muscle will have a lesser/ blunted repair process compared to young muscle.

To meet the aims of this study and to answer the hypothesis, this study protocol is as follows:

Baseline functional, metabolic and molecular values are obtained via functional testing and a muscle biopsy. Participants then perform eccentric exercise designed to induce functional decline and muscle soreness and the contralateral leg performs concentric exercise which isn't designed to induce soreness or functional decline. Using a time-course, various metabolic and molecular measures are taken prior to and up to 7 days post exercise to understand the mechanisms underlying muscle repair. In addition the use of a novel amino acid tracer (D2O) will allow for synthesis measures over the duration of the study rather than the typical tracer techniques which only capture ~12 hours of synthesis.

Description:

Participation in this study requires participants to attend the laboratory fasted on 5 occasions spread over a period of 12 days.

Participants will report to the laboratory on the first visit for a blood sample and muscle biopsy. In order to measure muscle metabolism participants will also consume 'heavy water', which will also require participants to provide daily saliva swabs.

After 96 hours participants will be asked to arrive at the laboratory to perform a bout of heavy exercise on one leg to induce sensations of muscle soreness in the days following exercise. Investigators will then collect a blood sample and muscle biopsy from the exercised leg and do exercise tests. After this, participants will perform another bout of exercise on the other leg that will also be followed immediately by a blood sample, muscle biopsy and exercise tests. This second exercise bout is not designed to induce sensations of muscle soreness. After 5 hours , exercise tests will be performed and a further blood sample and biopsies from both legs will be collected.

Approximately, 21 hours after exercise (visit 3) participants will be asked to return to the lab for a short infusion (2.5 hour duration) of 2-deoxyglucose (2DOG), which allows investigators to measure glucose uptake. After the infusion, a blood and a muscle biopsy will be taken from each leg followed by exercising testing. Participants will then report back to the laboratory for exercise testing, a blood sample and a single muscle biopsy from both legs at 72 (visit 4) and 168 hours (visit 5) after the initial exercise session.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: March 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 16-30 kg/m2 BMI

• Male

• Sedentary

• 18-28 years or 65-75 years

Exclusion Criteria:

• Active cardiovascular disease

• Cerebrovascular disease including previous stroke or aneurysm

• Respiratory disease including pulmonary hypertension or chronic obstructive pulmonary disease

• Metabolic disease including:

• hyper/ hypo parathyroidism or thyroidism

• Cushing's disease

• Type 1 or 2 diabetes

• Active inflammatory bowel disease

• Renal disease

• Malignancy

• Recent steroid treatment (within 6 months), or hormone replacement therapy

• Clotting dysfunction

• Musculoskeletal or neurological disorders medication that affects muscle metabolism ie. paracetamol or non steroidal anti inflammatories (NSAID's)

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Healthy

Intervention

Other:
• Exercise
One leg eccentric exercise: 7 sets of 10 repetitions at 80% 1 repetition maximum Contralateral leg concentric exercise: 7 sets of 10 repetitions at 80% 1 repetition maximum 2 mins rest between sets

Locations

Country	Name	City	State
United Kingdom	MRC-ARUK Centre of Excellence for Musculoskeletal Ageing Research, Division of Metabolic and Molecular Physiology, Postgraduate Entry Medical School, Royal Derby Hospital	Derby	Derbyshire

Sponsors (1)

Lead Sponsor	Collaborator
University of Nottingham

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in protein synthesis (fractional synthesis rate) in response to eccentric exercise		Up to one week after exercise	No