Counteracting Age-related Loss of Skeletal Muscle Mass (CALM)

Study Overview
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Brief Summary
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Up to 66 healthy elderly individuals (at least 65 years old) are recruited as subjects. They will be recruited as a subgroup to protocol ID: H-4-2013-070. Upon inclusion, each individual will be randomized into one of the five groups stratified according to gender (M/F) and 30s chair stand (<16 OR ≥16). The five groups are: Heavy Resistance Training (N=12), Light Intensity Training (N=12), Protein Whey (N=15), Protein Collagen (N=15) and Carbohydrate (N=12). The individuals randomized into one of the supplementation groups (Protein Whey, Protein Collagen or Carbohydrate) will be blinded to the supplement content. Assessments will be performed at Baseline (before intervention start) and after 12 months of intervention. The primary outcomes are measures of muscle protein synthesis rate measured as the fractional synthesis rate from Baseline to 12 months of intervention. The hypotheses are i) that basal and protein-stimulated muscle protein synthesis rates are elevated in the exercise training groups after 12 months of intervention. ii) prolonged intake of protein of different quality will improve the muscle protein synthetic response to protein intake after 12 months of intervention.

Official Title
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Counteracting Age-related Loss of Skeletal Muscle Mass

Conditions
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Sarcopenia, Muscle Loss

Intervention / Treatment
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* Procedure: Heavy Resistance Training
* Procedure: Light Intensity Training
* Dietary Supplement: Protein Whey
* Dietary Supplement: Protein Collagen
* Dietary Supplement: Carbohydrate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy, independently living Age at least 65 years Exclusion Criteria: Subjects dependent on help/nursing etc. Chronic medical diseases: diabetes mellitus, clinical knee or hip osteoarthritis, other types of arthritis or connective tissue disorders, active cancer, renal diseases, severe chronic obstructive pulmonary disease, cardiac arrhythmias or known decreased left ventricular ejection fraction, lactose or gluten intolerance, chronic inflammatory bowel diseases, non-treated hyper/hypothyroidism, dementia Surgical diseases: Bone, muscle, tendon or joint injuries compromising participation in exercise regimens Implanted magnetic devices incompatible with MRi-scanning Weekly alcohol consumption > 21 units (1 unit equals 4 g of ethanol) for men and > 14 for women Medicine except acetylsalicylic acid, paracetamol, thyroid function hormones, statins in doses above 40 mg/day or if combined with subjective myalgia, ACE-inhibitors, angiotensin II blockers, beta-blockers, calciumantagonists, proton-pump inhibitors, thiazides, potassium-sparring diuretics and loop diuretics 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: 65 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Heavy Resistance Training<br>Heavy Resistance Training of the lower extremities three times weekly in combination with two daily 20 g whey protein and 10 g carbohydrate supplementations for 52 weeks. | Procedure: Heavy Resistance Training<br>* Supervised Heavy Resistance Training three times weekly for 52 weeks.<br>Dietary Supplement: Protein Whey<br>* Two daily 20 g whey protein and 10 g carbohydrate supplementations for 52 weeks.<br>|
| Experimental: Light Intensity Training<br>Home-based Light Intensity Training of the lower extremities three-five times weekly in combination with two daily 20 g whey protein and 10 g carbohydrate supplementations for 52 weeks. | Procedure: Light Intensity Training<br>* Home-based Light Intensity Training three-five times weekly for 52 weeks.<br>Dietary Supplement: Protein Whey<br>* Two daily 20 g whey protein and 10 g carbohydrate supplementations for 52 weeks.<br>|
| Active Comparator: Protein Whey<br>Two daily 20 g whey protein and 10 g carbohydrate supplementations for 52 weeks. | Dietary Supplement: Protein Whey<br>* Two daily 20 g whey protein and 10 g carbohydrate supplementations for 52 weeks.<br>|
| Active Comparator: Protein Collagen<br>Two daily 20 g collagen protein and 10 g carbohydrate supplementations for 52 weeks. | Dietary Supplement: Protein Collagen<br>* Two daily 20 g collagen protein and 10 g carbohydrate supplementations for 52 weeks.<br>|
| Placebo Comparator: Carbohydrate<br>Two daily 30 g carbohydrate supplementations for 52 weeks. | Dietary Supplement: Carbohydrate<br>* Two daily 30 g carbohydrate supplementations for 52 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Basal overnight fasted muscle protein synthesis rate. | Overnight fasting muscle protein synthesis will be measured at Baseline and after 12 months intervention by applying stable isotope amino acid tracer techniques and calculating the fractional synthesis rates. | Baseline and 12 months | 
| Muscle protein synthesis rate response to protein intake from basal overnight fasted state. | Change in the response of muscle protein synthesis rate to a single intake of 20 g whey protein and 10 g carbohydrate from the basal overnight fasted state from Baseline to 12 months intervention. Statistical analysis: Outcome 1 will be subtracted outcome 2 to calculate the difference FSR at baseline and 12 month respectively. The difference at baseline will be subtracted the difference at 12 month to calculate the delta difference. This delta difference will be analyzed as a modified intention-to-treat as well as per protocol, and we will test the following groups against each other using one-way analysis of variance of the relative group changes from baseline to 12 months: (1) WHEY vs. COLL vs. CARB and (2) HRTW vs. LITW vs. WHEY | Baseline and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle protein turnover molecular signaling and gene expression | Muscle protein turnover regulation signaling and gene expression will be measured in the muscle tissue obtained for muscle protein synthesis measurements. Protein and protein activation status will be analysed by Western blot techniques. Gene expressions will be analysed by real time RT-PCR techniques. | Baseline and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sarcopenia, Frailty, Ageing, Protein supplementation, Protein quality, Exercise training, Muscle protein turnover