Physical Activity as Intervention Against Age-related Loss of Muscle Mass and Function

Study Overview
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Brief Summary
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A minimum of 450 healthy individuals (62-70 years old) will be recruited. Each individual will be randomized into one of three groups stratified according to gender (M/F), BMI (≤28/>28), and 30 sec chair stand (≤11/>11). The three groups are Heavy resistance training (n=150), moderate intensity training (n=150), and control (n=150, no training). Assessments will be performed at baseline, after 12 months of intervention. Furthermore, follow up will be performed after 2,4,7, and 10 years. The primary outcome is change in leg extensor power after the intervention and during follow up. The primary hypothesis is that by applying the intention-to-treat analysis, the moderate intensity training group will increase leg extensor power just as much as the heavy resistance training group. The two training groups will increase muscle power more than the control group.

Detailed Description
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Retirement has been recognized as a critical turning point in determining physical activity behaviours in old age. The literature gives a varying picture regarding change in physical activity level with work retirement but often a reduction in total physical activity has been reported. Retirement typically takes place at a time where the skeletal muscle mass, -strength and -power declines by 1-3% per year. Interventions to promote physical activity in adults aged 55 to 70 years have been shown to be effective at 12 months but it is very unclear if the effect is maintained thereafter. Both exercise at home or at a center improves health and physical function - but home based programs appear to be superior to center based programs in terms of adherence to exercise especially in the long-term. In older adults, strength training at 60% of 1RM has been shown to be sufficient for large effect on muscle function and muscle protein synthesis, and potentially lower loads (45-60% 1RM) have effect when adding more repetitions. The overall objective of the study is to assess the long-term effects of 12 month of supervised high-intensity center based resistance training or guided moderate-intensity home-based resistance training relative to a non-exercising control group upon muscle power, -strength and -mass, physical function, physical activity level and health in older people around the time of retirement. The hypotheses are: Supervised high-intensity center based resistance training over one year results in the best improvement in muscle power and bodily function Guided moderate-intensity home-based resistance training will result in a more active lifestyle and thus in sustained elevated activity level after the 1-year intervention period. Thus in the long run (several years) guided moderate-intensity home-based resistance training has superior effects compared to supervised high-intensity center based resistance training upon functional ability, health and potentially also cognitive function. 450 participants recruited through advertisements in local newspapers will be included in this three-armed, single-blinded randomized trial. After baseline assessment they will be randomized to one year of 1) supervised, high-intensity progressive, resistance training conducted in machines three times weekly in a local fitness center 2) guided moderate-intensity home-based resistance training conducted with elastic bands and body weight three times weekly. Guided means that the participants are offered supervised resistance training once weekly in addition to home based resistance training 2 times weekly or 3) various social and cultural activities that do not require physical activity. All participants complete a wide range of tests before and after the 12 months intervention period and the primary time point for outcome assessment will be at 12 month. The same test battery is conducted in the subsequent years (2, 4, 7, and 10 years later) as a follow-up.

Official Title
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Physical Activity as Intervention Against Age-related Loss of Muscle Mass and Function

Conditions
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Muscle Weakness, Muscle Loss, Sarcopenia, Physical Activity

Intervention / Treatment
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* Other: Heavy resistance training
* Other: Moderate intensity training
* Other: Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Independently living men and women Between 62 and 70 years Exclusion Criteria: Subjects dependent on help/nursing etc. Severe chronic obstructive pulmonary disease, cardiac arrhythmias or known decreased left ventricular ejection fraction, non-treated hyper/hypothyroidism, dementia, active cancer. Surgical diseases: Bone, muscle, tendon or joint injuries compromising participation in exercise regimens. Implanted magnetic devices incompatible with MRi-scanning. >1 hour of exercise weekly, except light activities such as stretching/gymnastics and bike-riding/walking as transportation.

Ages Eligible for Study
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Minimum Age: 62 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Heavy resistance training<br>Heavy resistance training of the lower and upper extremities three times weekly for 52 weeks. | Other: Heavy resistance training<br>* Supervised heavy resistance training three times weekly for 52 weeks.<br>|
| Experimental: Moderate intensity training<br>Home-based moderate intensity training of the lower and upper extremities three times weekly for 52 weeks. | Other: Moderate intensity training<br>* Moderate intensity training supervised once weekly and home based unsupervised two times weekly for 52 weeks.<br>|
| Experimental: Control<br>No training | Other: Control<br>* No training<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in leg extensor power | Unilateral leg extension power measured in the Leg Extensor Power Rig device (Nottingham). The primary time interval for assessment of the primary outcome measure is from baseline to 12 months intervention. The statistical evaluation of the primary outcome measure is done by applying a two way ANOVA test comparing the three groups before/after the intervention and during follow up (1,2,4,7, and 10 years). | Baseline, 1, 2, 4, 7, and 10 years follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in quadriceps cross sectional area | MRI scanning of thigh muscle composition | Baseline, 1, 2, 4, 7, and 10 years | 
| Change in maximal isometric quadriceps strength | Unilateral maximal isometric quadriceps strength measured in the Good Strength device. | Baseline, 1, 2, 4, 7, and 10 years | 
| Change in 30 s chair stand performance | Number of stand-ups from a chair in 30 seconds | Baseline, 1, 2, 4, 7, and 10 years | 
| Change in 400 m gait speed | The time used for walking 400 m (20 m course) | Baseline, 1, 2, 4, 7, and 10 years | 
| Change in whole body composition and bone mineral density as well as lumbar spine and femoral neck bone mineral density | Body composition (fat mass, lean mass and bone mass) evaluated by whole-body and regional (lumbar spine and femoral neck) dual energy x-ray absorptiometry (DXA)-scanning. | Baseline, 1, 2, 4, 7, and 10 years | 
| Change in grip strength | Isometric hand grip strength (Saehan dynamometer) | Baseline, 1, 2, 4, 7, and 10 years | 
| Change in perceived age | Determination of perceived age from facial and whole-body photographs | Baseline, 1, 2, 4, 7, and 10 years | 
| Change in blood parameters and anthropometry | Measuring 1) blood levels of inflammatory markers (CRP, TNFa, and IL-6) and HbA1c, plasma lipids. 2) Weight, abdominal circumference, blood pressure. | Baseline, 1, 2, 4, 7, and 10 years | 
| Change in physical activity level | Wearing a pedometer device (ActivPal) for 5 continuous days. Questionnaire: PASE (Physical Activity Scale for the Elderly). | Baseline, 1, 2, 4, 7, and 10 years | 
| Change in Exercise self-efficacy | Questionnaire: Exercise Self-efficacy Scale. | Baseline, 1, 2, 4, 7, and 10 years | 
| Change in Health Related Quality of Life | Questionnaire: SF36. | Baseline, 1, 2, 4, 7, and 10 years | 
| Changes in brain structure and function | MRI scanning of the regional brain structure and function | Baseline, 1, 2, 4, 7, and 10 years | 
| Change in cognitive ability | Questionnaire: IST 2000-R | Baseline, 1, 2, 4, 7, and 10 years | 
| Change in personality | Questionnaire: NEO-FFI | Baseline, 1, 2, 4, 7, and 10 years | 
| Change in mental symptoms | Questionnaire: SCL-90 | Baseline, 1, 2, 4, 7, and 10 years | 
| Adherence to training interventions | Questionnaire developped specifically for the LISA study by the authores | 2, 4, 7, 10 years |