Sarcopenia, Muscle Loss
Conditions
Keywords
Frailty, Ageing, Protein supplementation, Protein quality, Gut microbiota, Metabolome, Exercise training, Sarcopenia
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.
Interventions
PROCEDUREHeavy Resistance Training
Supervised Heavy Resistance Training three times weekly for 52 weeks.
PROCEDURELight Intensity Training
Home-based Light Intensity Training three-five times weekly for 52 weeks.
DIETARY_SUPPLEMENTProtein Whey
Two daily 20g whey protein and 10g carbohydrate supplementations for 52 weeks.
DIETARY_SUPPLEMENTProtein Collagen
Two daily 20g collagen protein and 10g carbohydrate supplementations for 52 weeks.
DIETARY_SUPPLEMENTCarbohydrate
Two daily 30g carbohydrate supplementations for 52 weeks.
Sponsors
University of Copenhagen
Arla Foods
Bispebjerg Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in muscle cross sectional area | Baseline, 6, 12, and 18 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in quadriceps muscle isokinetic strength | Baseline, 6, 12 and 18 months | Unilateral knee extension (concentric) strength measured in the KinCom device at an angular velocity of 60 degrees/sec. |
| Change in leg extension muscle power | Baseline, 6, 12 and 18 months | Unilateral leg extension power measured in the Powerrig device. |
| Change from baseline in muscle structure and signalling | Baseline and 12 months | 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. |
| Change in gut microbiota composition. | Baseline, 6 and 12 months (and 18 months on a subset of samples). | Molecular biology based methods incl. high throughput sequencing aided by classical, culture-based microbiological techniques as needed. |
| Change in faecal metabolome. | Baseline, 6 and 12 months (and 18 months on a subset of samples). | NMR of faecal samples. |
| Change in 30 s chair stand | Baseline, 6, 12 and 18 months | Number of stand-ups from a chair in 30 seconds. |
| Change in plasma metabolome. | Baseline, 6 and 12 months (and 18 months on a subset of samples). | Nuclear magnetic resonance (NMR) of plasma samples. |
| Change in whole body composition and bone mineral density | Baseline, 6, 12 and 18 months | 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. |
| Change in quadriceps muscle isometric strength | Baseline, 6, 12 and 18 months | 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). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in gait speed | Baseline, 6, 12 and 18 months | 400 m gait speed. |
| Change in grip strength | Baseline, 6, 12 and 18 months | Isometric hand grip strength. |
| Change in tendon biomechanical properties | Baseline and 12 months | Measurements of tendon biomechanical properties. |
| Questionnaires and interviews | Baseline and 12 months | Short Form 36, Pittsburgh Sleep Scale Questionnaire, questionnaires on lifestyle, life history, supplement palatability and interviews and observations of subjects with focus on changes in lifestyle as result of intervention. |
| Change in daily macronutrient intake | Baseline, 1.5/2 and 12 months | 3-days self-report of food and beverage intake. |
| Change in habitual activity | Baseline, 6, 12 and 18 months | Evaluated by 4 days continuous monitoring by a pedometer device (ActivPal). |
| Questionnaire on acceptance of supplements | Weekly for first 3 months and every 3rd month until 12 months | Questionnaires on acceptance of supplementation |
| Change in glucose handling measured by a OGTT | Baseline and 12 months | Completion of an oral glucose tolerance test (OGTT) |
| Change in vitamin B12 and related metabolite concentrations in blood | Baseline, 6, 12 and 18 months | Concentration of total B12, B12 available for cells (holoTC), and methylmalonate (MMA). |
| Change in blood parameters and anthropometry | Baseline, 6, 12 and 18 months | Blood: HbA1c, plasma lipids, vitamin B12 and related metabolites. Anthropometry: Weight, abdominal circumference. Blood pressure. |
Countries
Denmark
Outcome results
None listed