Sarcopenia Prevention With a Targeted Exercise and Protein Supplementation Program

Study Overview
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Brief Summary
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Physical inactivity and protein malnutrition have been implicated to be key and modifiable causes of enhanced muscle mass loss among seniors. However, the individual benefit, as well as the additive or possibly interactive benefit of exercise and Protein supplementation on fall prevention has yet to be confirmed in a large clinical trial. This study aims to test the individual and combined effect and cost-effectiveness of a simple home exercise program and / or protein supplementation on the risk of falling in seniors at high risk of progressive muscle mass loss and sarcopenia.

Detailed Description
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The number of seniors age 75 and older is predicted to double by 2030, as is the number of seniors with mobility disability, physical frailty and resulting consequences, such as falls and loss of autonomy. This causes an enormous challenge to the individual, to medical care, and the society as a whole. A condition that is considered central to the development of physical frailty and its consequences is sarcopenia, the loss of muscle mass and strength. To date sarcopenia is underdiagnosed in clinical care and effective treatments for sarcopenia are missing. This study aims to test the individual and combined effect and cost-effectiveness of a simple home exercise program and / or protein supplementation on the risk of falling in seniors at high risk of progressive muscle mass loss and sarcopenia. The STRONG trial will be a 2x2 factorial design multi-centre double-blind randomized controlled clinical trial among 800 senior men and women; study duration is 12 months. The primary endpoint is the rate of falling. Key secondary endpoints include functional decline, and the proportion of seniors with frailty, sarcopenia, and loss of autonomy. STRONG will further assess the cost-effectiveness of the interventions based on health care utilization data collected every 2 months from each participant and observed incidence of the endpoints. Mechanistic endpoints include change in muscle mass by DXA(arms and legs), change in myostatin levels, and muscle quality (based on MRI). The interventions are (1) a simple home exercise program (a validated strength-enhancing or a control joint flexibility exercise program) to be performed 3x30 minutes/week; and (2) protein supplementation (either 20g of whey protein or isocaloric powder given in two portions for breakfast and dinner each day). All participants will receive a control dose of 24'000 IU vitamin D per month (equivalent to 800 IU vitamin D/day) to ensure that over 97% of STRONG participants will be vitamin D replete (25-hydroxyvitamin D > 20 ng/ml) during the course of the trial. The trial will have clinical visits at baseline, 6 months, and 12 months. In between clinical visits, telephone interviews will be performed every 2 months.

Official Title
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Sarcopenia Prevention With a Targeted Exercise and Protein Supplementation Program

Conditions
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Sarcopenia, Frailty, Malnutrition; Protein, Fall

Intervention / Treatment
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* Dietary Supplement: Protein Supplement
* Dietary Supplement: Protein-free Supplement
* Procedure: Active Exercise
* Procedure: Control Exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 1 of 5 frailty criteria, definition by Linda Fried: 1) weight loss of > 4.5 kg in the last 12 months; 2) reduced grip strength in Martin Vigorimeter test: ♂ ≤ 64 kPa, ♀ ≤ 42 kPa; 3) standardized question on exhaustion as published by Fried et al.; 4) gait speed < 1 m/s; 5) 6-minute walk test < 300 meters and/or Injurious (any injury) low trauma fall in the last 12 months prior to enrollment Reduced protein intake defined as a score ≤ 0.5 at item K of the Mini Nutritional Assessment (MNA) Community-dwelling or assisted living Exclusion Criteria: Mini-mental state examination (MMSE) < 24 (inability to follow the study procedures and give written informed consent) Inability to come to the trial centers Inability to walk at least 3 meters with or without walking aid Severe kidney impairment (Glomerular filtration rate [GFR] < 30 ml/min) Inability to follow exercise instruction or inability to take protein powder mixed in drink or food (test at baseline screening examination) Severe gait impairment or diseases with a risk of recurrent falling (due to conditions such as, e.g. Parkinson's disease/syndrome, Hemiplegia after stroke, symptomatic stenosis of the spinal canal, polyneuropathy, epilepsy, recurring vertigo, recurring syncope) Major visual or hearing impairment or other serious illness that would preclude participation (e.g. alcohol abuse, alcoholic disease) Inability to read/speak/write in German (necessary to follow instructions incl. STRONG exercise manual) Living in a nursing home Contraindication to treatment (e.g. allergy) Contraindication to the vitamin D standard of care therapy

Ages Eligible for Study
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Minimum Age: 75 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: Factorial Assignment
Interventional Model Description: 2x2 factorial design
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Protein Supplement plus Active Exercise<br>Participants will ingest twice daily 23.7 g of L-leucine-enriched whey protein isolate powder (equivalent to 20 g of Protein) and perform a simple home exercise strength program (3x30 minutes/week) | Dietary Supplement: Protein Supplement<br>* Predosed protein powder; can be added to various dishes and drinks<br>* Other names: Moltein® Ready-to-Shake;Procedure: Active Exercise<br>* Program includes five strength exercises that can be easily performed at home<br>|
| Active Comparator: Protein-free Supplement plus Active Exercise<br>Participants will ingest twice daily 23.7 g of a protein-free, isocaloric powder blend and perform a simple home exercise strength program (3x30 minutes/week) | Dietary Supplement: Protein-free Supplement<br>* Predosed protein-free powder; can be added to various dishes and drinks<br>Procedure: Active Exercise<br>* Program includes five strength exercises that can be easily performed at home<br>|
| Active Comparator: Protein Supplement plus Control Exercise<br>Participants will ingest twice daily 23.7 g of L-leucine-enriched whey protein isolate powder (equivalent to 20 g of Protein) and perform a joint flexibility home exercise program (3x30 minutes/week) | Dietary Supplement: Protein Supplement<br>* Predosed protein powder; can be added to various dishes and drinks<br>* Other names: Moltein® Ready-to-Shake;Procedure: Control Exercise<br>* Program includes five flexibility exercises that can be easily performed at home<br>|
| Sham Comparator: Protein-free Supplement plus Control Exercise<br>Participants will ingest twice daily 23.7 g of a protein-free, isocaloric powder blend and perform a joint flexibility home exercise program (3x30 minutes/week) | Dietary Supplement: Protein-free Supplement<br>* Predosed protein-free powder; can be added to various dishes and drinks<br>Procedure: Control Exercise<br>* Program includes five flexibility exercises that can be easily performed at home<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of falling | The circumstances and injuries associated with the fall will be ascertained with a questionnaire. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional decline (change in lower extremity function) | will be assessed with the Short Physical Performance Battery (SPPB) | Baseline, 6, and 12 months | 
| Proportion of seniors with any falls and injurious falls | using the same method as for the primary endpoint | every 2 months over 12 months | 
| Proportion of seniors with established frailty | Frailty will be defined as 3 out of the following 5 criteria are met: 1) weight loss of > 4.5 kg in the last 12 months; 2) reduced grip strength in Martin Vigorimeter test: ♂ ≤ 64 kPa, ♀ ≤ 42 kPa; 3) standardized question on exhaustion as published by Fried et al.; 4) gait speed < 1 m/s; 5) 6-minute walk test < 300 meters | Baseline, 6, and 12 months | 
| Proportion of seniors with sarcopenia | will be assessed both with the Baumgartner definition (muscle mass alone) and the European Working Group definition by Cruz-Jentoft24 (composite definition of muscle mass and impaired grip strength or gait speed) | Baseline, 6, and 12 months | 
| Proportion of seniors admitted to nursing homes (loss of autonomy) | participants will be asked at visits/phone calls | every 2 months over 12 months | 
| Change in gait speed | Gait speed will be measured over a distance of 4 meters. The participants will be asked to walk in their usual pace | Baseline, 6, and 12 months | 
| Change in reaction time | Reaction time will be assessed with repeated chair stands (5 repeats as part of the SPPB) | Baseline, 6, and 12 months | 
| Change in grip strength | Measured with Martin Vigorimeter | Baseline, 6, and 12 months | 
| Change in aerobic capacity | Aerobic capacity will be assessed with the 6 minute walk test. A walked distance of < 300 m will be used as a frailty criteria | Baseline, 6, and 12 months | 
| Change in muscle mass (arms and legs) | will be measured with IDXA machines (intelligent dual x-ray absorptiometry by GE Healthcare) | Baseline, 6, and 12 months | 
| Change in bone mineral density (hip and lumbar spine) | will be measured with IDXA machines (intelligent dual x-ray absorptiometry by GE Healthcare) | Baseline and 12 months | 
| Change in physical activity | will be assessed by an excerpt from the Nurses' Health Study (NHS) questionnaire | Baseline, 6, and 12 months | 
| Change in quality of life | will be assessed using the German Version of EuroQuol EQ5D-3L questionnaire according to the Austrian reference scale | Baseline, 6, and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Protein supplementation, Home exercise program, Falls prevention, Seniors, Autonomy