Combined Effects of Resistance Training and Nutritional Supplements in the Treatment of Sarcopenia

Study Overview
=================
Brief Summary
-----------------
Age-related sarcopenia is associated with increased morbidity, mortality, disability and reduced resistance to metabolic stress. The aim of this study is to assess the effects of resistance training, associated or not with oral nutritional supplements, on skeletal muscle mass in sarcopenic subjects. This is a prospective randomised controlled single-centre study that will last two years, three months for a participant. 200 healthy elderly (70-80 years old) subjects will be screened for sarcopenia by dual energy X-ray absorptiometry. 128 sarcopenic subjects will be randomized into 4 groups: group 1: controls group 2: oral nutritional supplement (260 kcal and 20 g protein per day) group 3: resistance training (3 times per week) group 4: oral nutritional supplement + resistance training Every subject will be assessed at the beginning and at the end of 12 weeks of intervention on: muscle mass (DXA) muscle function (dynamometers) hormonal (testosterone, GH, IGF-1, cortisol) and inflammatory (IL-6, TNF-alpha) profiles food intake. Ten subjects in group 4 will undergo a muscle biopsy (quadriceps) before and after the intervention in order to explore protein and mRNA levels of the mTOR pathway, which may be involved in sarcopenia.

Detailed Description
-----------------
Age-related sarcopenia is a common situation defined by muscle mass and function loss in an otherwise healthy elderly person. Epidemiological data from the USA show 49% of men and 72% of women to suffer from sarcopenia. Few data is available on the French population. Sarcopenia is associated with increased morbidity, mortality, disability and reduced resistance to metabolic stress. Resistance training and nutrition are two non-pharmaceutical methods that may be able to prevent several age-related condition. The aim of this study is to assess the effects of resistance training, associated or not with oral nutritional supplements, on skeletal muscle mass (expressed as skeletal muscle mass index) in sarcopenic subjects. This is a prospective randomised controlled single-centre study that will last two years, three months for a participant. 200 healthy elderly (70-80 years old) subjects will be screened for sarcopenia by dual energy X-ray absorptiometry. 128 sarcopenic subjects will be randomized into 4 groups: group 1: controls group 2: oral nutritional supplement (260 kcal and 20 g protein per day) group 3: resistance training (3 times per week) group 4: oral nutritional supplement + resistance training Every subject will be assessed at the beginning and at the end of 12 weeks of intervention on: muscle mass (DXA) muscle function (dynamometers) hormonal (testosterone, GH, IGF-1, cortisol) and inflammatory (IL-6, TNF-alpha) profiles food intake. Ten subjects in group 4 will undergo a muscle biopsy (quadriceps) before and after the intervention in order to explore protein and mRNA levels of the mTOR pathway, which may be involved in sarcopenia. We expect to show that sarcopenia can be improved by 12 weeks of resistance training and that this improvement can be potentialized by oral nutritional supplements (with a stimulation of the mTOR pathway), and that oral nutritional supplements alone will affect neither muscle mass nor function.

Official Title
-----------------
Combined Effects of Resistance Training and Nutritional Supplements in the Treatment of Sarcopenia

Conditions
-----------------
Sarcopenia

Intervention / Treatment
-----------------
* Dietary Supplement: Fortimel Extra®
* Other: resistance training
* Other: combined treatment


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age between 70 and 80 years Stable weight (± 1 kg) during the last three months Informed consent signed Affiliated with the French Sécurité Sociale Non-inclusion criteria Chronic cachectic condition: cancer, chronic respiratory failure, advanced organ failure, hyperthyroidism, rheumatoid arthritis, AIDS, type 1 diabetes Drugs affecting muscle mass (e.g. steroids) Condition (clinical or EKG) significantly affecting physical capacities and/or contra-indicating resistance training Habitual practice of resistance training Habitual intake of nutritional supplements Known coagulation disorders (for muscle biopsy) Known allergy to lidocaine (for muscle biopsy)

Ages Eligible for Study
-----------------
Minimum Age: 70 Years
Maximum Age: 80 Years

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: 1<br>No intervention | |
| Experimental: 2<br>patient receiving oral nutrition supplement | Dietary Supplement: Fortimel Extra®<br>* 260kcal and 20g protein per day<br>|
| Experimental: 3<br>resistance training | Other: resistance training<br>* 3 sessions of resistance training per week<br>|
| Experimental: 4<br>patients receiving resistance training and oral nutritional supplement | Other: combined treatment<br>* 260kcal and 20g protein per day 3 sessions of resistance training per week<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| muscle mass (DXA) |  | D0 and after 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| muscle function (dynamometers), hormonal (testosterone, GH, IGF-1, cortisol) and inflammatory (IL-6, TNF-alpha) profiles, food intake, ± muscle biopsy. |  | D0 and after 12 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
sarcopenia, elderly, resistance training, oral nutritional supplement