Counteracting Age-related Loss of Skeletal Muscle Mass

Study Overview
=================
Brief Summary
-----------------
Up to approximately 205 (dependent on drop-out rate) healthy elderly individuals (at least 65 years old) are recruited as subjects. 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=30-35), Light Intensity Training (N=30-35), Protein Whey (N=40-50), Protein Collagen (N=40-50) and Carbohydrate (N=30-35). 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 6 and 12 months of intervention and again at 18 months (after 6 months of follow up). The primary outcome is change in quadriceps muscle cross sectional area from Baseline to 12 months of intervention. The primary hypothesis is that by applying the intension-to-treat analysis, the Light Intensity Training group will increase quadriceps muscle cross sectional area just as much as the Heavy Resistance Training group. The two training groups will gain more muscle mass than the Protein Whey group, which will gain more than the Protein Collagen and the Carbohydrate groups that will loose quadriceps muscle cross sectional areas.

Official Title
-----------------
Counteracting Age-related Loss of Skeletal Muscle Mass

Conditions
-----------------
Muscle Loss, Sarcopenia

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


Participation Criteria
=================
Eligibility Criteria
-----------------
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 4g of ethanol) for men and > 14 for women. Medicine except acetylsalicylic acid, paracetamol, thyroid function hormones, statins in doses above 40mg/day or if combined with subjective myalgia, ACE-inhibitors, Angiotensin II blockers, beta-blockers, calciumantagonists, proton-pump inhibitors, thiazides, potassium-sparing 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
-----------------
Minimum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

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 20g whey protein and 10g 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 20g whey protein and 10g 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 20g whey protein and 10g 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 20g whey protein and 10g carbohydrate supplementations for 52 weeks.<br>|
| Active Comparator: Protein Whey<br>Two daily 20g whey protein and 10g carbohydrate supplementations for 52 weeks. | Dietary Supplement: Protein Whey<br>* Two daily 20g whey protein and 10g carbohydrate supplementations for 52 weeks.<br>|
| Active Comparator: Protein Collagen<br>Two daily 20g collagen protein and 10g carbohydrate supplementations for 52 weeks. | Dietary Supplement: Protein Collagen<br>* Two daily 20g collagen protein and 10g carbohydrate supplementations for 52 weeks.<br>|
| Placebo Comparator: Carbohydrate<br>Two daily 30g carbohydrate supplementations for 52 weeks. | Dietary Supplement: Carbohydrate<br>* Two daily 30g carbohydrate supplementations for 52 weeks.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in muscle cross sectional area | MRi scans of quadriceps muscle cross sectional area. 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 groups: 1) Heavy Resistance Training vs. Light Intensity Training vs. Protein Whey and 2) Protein Whey vs. Protein Collagen vs. Carbohydrate. The statistical evaluation will be performed first as an intension-to-treat analysis and subsequently as a per-protocol analysis. Assessments are performed at 6 months as well and at 18 months (after 6 months follow up). Changes in muscle cross sectional area will be evaluated over 6 months from Baseline to 6 months, from 6 to 12 months, and from 12 months to 18 months. | Baseline, 6, 12, and 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in quadriceps muscle isometric strength | Isometric unilateral quadriceps force and rate of force development measured in the isokinetic dynamometer device (KinCom) during knee extension at the knee angle 70 deg (with 0 degrees being fully extended). | Baseline, 6, 12 and 18 months | 
| Change in quadriceps muscle isokinetic strength | Unilateral knee extension (concentric) strength measured in the KinCom device at an angular velocity of 60 degrees/sec. | Baseline, 6, 12 and 18 months | 
| Change in leg extension muscle power | Unilateral leg extension power measured in the Powerrig device. | Baseline, 6, 12 and 18 months | 
| Change from baseline in muscle structure and signalling | From muscle biopsies muscle fiber type distribution and size, capillary density, satellite cell count and activity, selected gene-expression targets and protein concentrations will be assessed. | Baseline and 12 months | 
| Change in gut microbiota composition. | Molecular biology based methods incl. high throughput sequencing aided by classical, culture-based microbiological techniques as needed. | Baseline, 6 and 12 months (and 18 months on a subset of samples). | 
| Change in faecal metabolome. | NMR of faecal samples. | Baseline, 6 and 12 months (and 18 months on a subset of samples). | 
| Change in faecal metabolome. | Gas chromatography mass spectrometry (GCMS) of faecal samples. | Baseline, 6 and 12 months (and 18 months on a subset of samples). | 
| Change in plasma metabolome. | Nuclear magnetic resonance (NMR) of plasma samples. | Baseline, 6 and 12 months (and 18 months on a subset of samples). | 
| Change in plasma metabolome. | GCMS of plasma samples. | Baseline, 6 and 12 months (and 18 months on a subset of samples). | 
| Change in 30 s chair stand | Number of stand-ups from a chair in 30 seconds. | Baseline, 6, 12 and 18 months | 
| Change in whole body composition and bone mineral density | Body composition (fat mass, lean mass and bone mass) evaluated by whole-body dual energy x-ray absorptiometry (DXA)-scanning. Bone mineral density at vertebrae L2-L4 and collum femoris evaluated by DXA-scanning. | Baseline, 6, 12 and 18 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Frailty, Ageing, Protein supplementation, Protein quality, Gut microbiota, Metabolome, Exercise training, Sarcopenia