Clinical trial NCT03417531: Sarcopenia Prevention With a Targeted Exercise and Protein Supplementation Program
Official title: Sarcopenia Prevention With a Targeted Exercise and Protein Supplementation Program
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Sarcopenia
Frailty
Malnutrition; Protein
Fall
Keywords: Protein supplementation
Home exercise program
Falls prevention
Seniors
Autonomy
Lead sponsor: University of Zurich
Sponsor class: OTHER
Collaborators: name: Swiss National Science Foundation
name: University Hospital, Zürich
name: University Geriatric Medicine Felix Platter, Basel, Switzerland
name: Omanda AG, Baar, Switzerland
name: Ferrari Data Solution
name: City Hospital Waid and Triemli, Zurich, Switzerland
name: Cantonal Hospital St. Gallen, Switzerland
name: University Hospital, Basel, Switzerland
First posted: 2018-01-31
Enrollment: 801
Sex: ALL
Minimum age (years): 75
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: 2x2 factorial design
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Rate of falling
timeFrame: 12 months
Secondary outcomes:
measure: Functional decline (change in lower extremity function)
timeFrame: Baseline, 6, and 12 months
measure: Proportion of seniors with any falls and injurious falls
timeFrame: every 2 months over 12 months
measure: Proportion of seniors with established frailty
timeFrame: Baseline, 6, and 12 months
measure: Proportion of seniors with sarcopenia
timeFrame: Baseline, 6, and 12 months
measure: Proportion of seniors admitted to nursing homes (loss of autonomy)
timeFrame: every 2 months over 12 months
measure: Change in gait speed
timeFrame: Baseline, 6, and 12 months
measure: Change in reaction time
timeFrame: Baseline, 6, and 12 months
measure: Change in grip strength
timeFrame: Baseline, 6, and 12 months
measure: Change in aerobic capacity
timeFrame: Baseline, 6, and 12 months
measure: Change in muscle mass (arms and legs)
timeFrame: Baseline, 6, and 12 months
measure: Change in bone mineral density (hip and lumbar spine)
timeFrame: Baseline and 12 months
measure: Change in physical activity
timeFrame: Baseline, 6, and 12 months
measure: Change in quality of life
timeFrame: Baseline, 6, and 12 months
Other outcomes:
measure: Health care utilization
timeFrame: every 2 months over 12 months
measure: Myostatin
timeFrame: Baseline, 6, and 12 months
measure: IGF-1
timeFrame: Baseline, 6, and 12 months
measure: CRP
timeFrame: Baseline, 6, and 12 months
measure: Kidney function
timeFrame: Baseline, 6, and 12 months
measure: 25-hydroxyvitamin D
timeFrame: Baseline, 6, and 12 months
measure: Fasting insulin levels
timeFrame: Baseline, 6, and 12 months
measure: Fasting blood glucose
timeFrame: Baseline, 6, and 12 months
measure: Change muscle quality (sub-sample of 140 participants)
timeFrame: Baseline and 12 months
measure: Any non-vertebral fracture
timeFrame: every 2 months over 12 months
measure: Mortality
timeFrame: every 2 months over 12 months
measure: Rate of SAEs in general
timeFrame: over 12 months
measure: Rate of SAEs related to study intervention
timeFrame: over 12 months
measure: Adherence to intervention (dietary supplement)
timeFrame: Baseline, 6, and 12 months
measure: Adherence to intervention (dietary supplement)
timeFrame: over 12 months
measure: Adherence to intervention (exercise)
timeFrame: over 12 months
measure: Covariate: Hearing
timeFrame: over 12 months
Locations:
city: Zurich
country: Switzerland
facility: Centre on Aging and Mobility, University of Zurich and City Hospital Waid and Triemli
state: ZH
city: Basel
country: Switzerland
facility: University Geriatric Medicine Felix Platter, Basel
Study officials:
affiliation: University of Zurich
name: Heike A. Bischoff-Ferrari, MD, DrPH
role: PRINCIPAL_INVESTIGATOR
References: