Sarcopenia Prevention With a Targeted Exercise and Protein Supplementation Program (STRONG)

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.

Study Overview

• Status: Recruiting
• Conditions: Frailty; Sarcopenia; Fall; Malnutrition; Protein
• Intervention / Treatment: Dietary supplement: Protein Supplement; Procedure: Active Exercise; Dietary supplement: Protein-free Supplement; Procedure: Control Exercise

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.

• Study Type: Interventional
• Enrollment (Anticipated): 800
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Heike A. Bischoff-Ferrari, MD, DrPH; Phone Number: +41 44 255 27 57; Email: heike.bischoff@usz.ch
• Study Contact Backup: Name: Lena Mink; Phone Number: +41 44 417 20 14; Email: Lena.Mink@usz.ch

Study Locations

• Switzerland
  • Basel, Switzerland, 4012
    • Recruiting
    • University Geriatric Medicine Felix Platter, Basel
    • Contact: Reto W Kressig, MD; Phone Number: +41 61 326 40 22; Email: RetoW.Kressig@felixplatter.ch
    • Contact: Stephanie Bridenbaugh, MD; Phone Number: +41 61 326 48 21; Email: Stephanie.Bridenbaugh@felixplatter.ch
    • Principal Investigator: Reto W Kressig, MD
  • ZH
    • Zurich, ZH, Switzerland, 8037
      • Recruiting
      • Centre on Aging and Mobility, University of Zurich and City Hospital Waid and Triemli
      • Contact: Lena Mink; Phone Number: +41 44 417 20 14; Email: Lena.Mink@usz.ch
      • Contact: Heike A Bischoff-Ferrari, MD, DrPH; Phone Number: +41 44 255 27 57; Email: Heike.Bischoff@usz.ch
      • Principal Investigator: Heike A Bischoff-Ferrari, MD, DrPH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 75 years and older (Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Protein Supplement plus Active Exercise; 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; Predosed protein powder; can be added to various dishes and drinks; Other Names: Moltein® Ready-to-Shake; Procedure: Active Exercise; Program includes five strength exercises that can be easily performed at home
Active Comparator: Protein-free Supplement plus Active Exercise; 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)	Procedure: Active Exercise; Program includes five strength exercises that can be easily performed at home; Dietary supplement: Protein-free Supplement; Predosed protein-free powder; can be added to various dishes and drinks
Active Comparator: Protein Supplement plus Control Exercise; 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; Predosed protein powder; can be added to various dishes and drinks; Other Names: Moltein® Ready-to-Shake; Procedure: Control Exercise; Program includes five flexibility exercises that can be easily performed at home
Sham Comparator: Protein-free Supplement plus Control Exercise; 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; Predosed protein-free powder; can be added to various dishes and drinks; Procedure: Control Exercise; Program includes five flexibility exercises that can be easily performed at home

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Health care utilization	assessed with a simple questionnaire to collect health care utilization information prospectively (MD visit, PT visit, hospitalizations in acute care etc)	every 2 months over 12 months
Myostatin	Blood Sample Assessment: Myostatin	Baseline, 6, and 12 months
IGF-1	Blood Sample Assessment: Insulin-like growth factor-1	Baseline, 6, and 12 months
CRP	Blood Sample Assessment: C-Reactive Protein	Baseline, 6, and 12 months
Kidney function	Blood Sample Assessment: creatinine	Baseline, 6, and 12 months
25-hydroxyvitamin D	Blood Sample Assessment: 25-hydroxyvitamin D	Baseline, 6, and 12 months
Fasting insulin levels	Blood Sample Assessment: fasting insulin levels	Baseline, 6, and 12 months
Fasting blood glucose	Blood Sample Assessment: fasting blood glucose	Baseline, 6, and 12 months
Change muscle quality (sub-sample of 140 participants)	Assessed with whole Body MRI's in a subsample of f140 participants	Baseline and 12 months
Any non-vertebral fracture	All fractures will be confirmed by x-ray or medical record.	every 2 months over 12 months
Mortality	will be assessed by personal contact	every 2 months over 12 months
Rate of SAEs in general	Serious Adverse Events	over 12 months
Rate of SAEs related to study intervention	Serious Adverse Events	over 12 months
Adherence to intervention (dietary supplement)	nitrogen excretion from 24-h/spot urine	Baseline, 6, and 12 months
Adherence to intervention (dietary supplement)	will be assessed by questionnaire and diary	over 12 months
Adherence to intervention (exercise)	will be assessed by questionnaire and diary	over 12 months
Covariate: Hearing	will be assessed by a hearing test	over 12 months

Collaborators and Investigators

• Sponsor: University of Zurich
• Collaborators: Swiss National Science Foundation; University Hospital, Basel, Switzerland; University Hospital, Zürich; Ferrari Data Solution; University Geriatric Medicine Felix Platter, Basel, Switzerland; Omanda AG, Baar, Switzerland; City Hospital Waid and Triemli, Zurich, Switzerland; Cantonal Hospital St. Gallen, Switzerland
• Investigators: Principal Investigator: Heike A. Bischoff-Ferrari, MD, DrPH, University of Zurich

Study record dates

Study Major Dates

• Study Start (Actual): June 25, 2018
• Primary Completion (Anticipated): July 1, 2024
• Study Completion (Anticipated): July 1, 2024

Study Registration Dates

• First Submitted: January 9, 2018
• First Submitted That Met QC Criteria: January 23, 2018
• First Posted (Actual): January 31, 2018

Study Record Updates

• Last Update Posted (Actual): May 16, 2023
• Last Update Submitted That Met QC Criteria: May 15, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Seniors; Protein supplementation; Autonomy; Home exercise program; Falls prevention
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Nutrition Disorders; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Muscular Atrophy; Atrophy; Severe Acute Malnutrition; Frailty; Sarcopenia; Malnutrition; Kwashiorkor
• Other Study ID Numbers: 2017-02045

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No