Counteracting Age-related Loss of Skeletal Muscle Mass (CALM)

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.

Study Overview

• Status: Completed
• Conditions: Sarcopenia; Muscle Loss
• Intervention / Treatment: Procedure: Heavy Resistance Training; Dietary supplement: Protein Whey; Procedure: Light Intensity Training; Dietary supplement: Protein Collagen; Dietary supplement: Carbohydrate

• Study Type: Interventional
• Enrollment (Actual): 208
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen NV, Denmark, 2400
    • Bispbebjerg Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Heavy Resistance Training; Heavy Resistance Training of the lower extremities three times weekly in combination with two daily 20g whey protein and 10g carbohydrate supplementations for 52 weeks.	Procedure: Heavy Resistance Training; Supervised Heavy Resistance Training three times weekly for 52 weeks.; Dietary supplement: Protein Whey; Two daily 20g whey protein and 10g carbohydrate supplementations for 52 weeks.
EXPERIMENTAL: Light Intensity Training; Home-based Light Intensity Training of the lower extremities three-five times weekly in combination with two daily 20g whey protein and 10g carbohydrate supplementations for 52 weeks.	Dietary supplement: Protein Whey; Two daily 20g whey protein and 10g carbohydrate supplementations for 52 weeks.; Procedure: Light Intensity Training; Home-based Light Intensity Training three-five times weekly for 52 weeks.
ACTIVE_COMPARATOR: Protein Whey; Two daily 20g whey protein and 10g carbohydrate supplementations for 52 weeks.	Dietary supplement: Protein Whey; Two daily 20g whey protein and 10g carbohydrate supplementations for 52 weeks.
ACTIVE_COMPARATOR: Protein Collagen; Two daily 20g collagen protein and 10g carbohydrate supplementations for 52 weeks.	Dietary supplement: Protein Collagen; Two daily 20g collagen protein and 10g carbohydrate supplementations for 52 weeks.
PLACEBO_COMPARATOR: Carbohydrate; Two daily 30g carbohydrate supplementations for 52 weeks.	Dietary supplement: Carbohydrate; Two daily 30g carbohydrate supplementations for 52 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in muscle cross sectional area	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.	Baseline, 6, 12, and 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in quadriceps muscle isometric strength	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).	Baseline, 6, 12 and 18 months
Change in quadriceps muscle isokinetic strength	Unilateral knee extension (concentric) strength measured in the KinCom device at an angular velocity of 60 degrees/sec.	Baseline, 6, 12 and 18 months
Change in leg extension muscle power	Unilateral leg extension power measured in the Powerrig device.	Baseline, 6, 12 and 18 months
Change from baseline in muscle structure and signalling	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.	Baseline and 12 months
Change in gut microbiota composition.	Molecular biology based methods incl. high throughput sequencing aided by classical, culture-based microbiological techniques as needed.	Baseline, 6 and 12 months (and 18 months on a subset of samples).
Change in faecal metabolome.	NMR of faecal samples.	Baseline, 6 and 12 months (and 18 months on a subset of samples).
Change in faecal metabolome.	Gas chromatography mass spectrometry (GCMS) of faecal samples.	Baseline, 6 and 12 months (and 18 months on a subset of samples).
Change in plasma metabolome.	Nuclear magnetic resonance (NMR) of plasma samples.	Baseline, 6 and 12 months (and 18 months on a subset of samples).
Change in plasma metabolome.	GCMS of plasma samples.	Baseline, 6 and 12 months (and 18 months on a subset of samples).
Change in 30 s chair stand	Number of stand-ups from a chair in 30 seconds.	Baseline, 6, 12 and 18 months
Change in whole body composition and bone mineral density	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.	Baseline, 6, 12 and 18 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in blood parameters and anthropometry	Blood: HbA1c, plasma lipids, vitamin B12 and related metabolites. Anthropometry: Weight, abdominal circumference. Blood pressure.	Baseline, 6, 12 and 18 months
Change in gait speed	400 m gait speed.	Baseline, 6, 12 and 18 months
Change in grip strength	Isometric hand grip strength.	Baseline, 6, 12 and 18 months
Change in tendon biomechanical properties	Measurements of tendon biomechanical properties.	Baseline and 12 months
Questionnaires and interviews	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.	Baseline and 12 months
Change in daily macronutrient intake	3-days self-report of food and beverage intake.	Baseline, 1.5/2 and 12 months
Change in habitual activity	Evaluated by 4 days continuous monitoring by a pedometer device (ActivPal).	Baseline, 6, 12 and 18 months
Questionnaire on acceptance of supplements	Questionnaires on acceptance of supplementation	Weekly for first 3 months and every 3rd month until 12 months
Change in glucose handling measured by a OGTT	Completion of an oral glucose tolerance test (OGTT)	Baseline and 12 months
Change in vitamin B12 and related metabolite concentrations in blood	Concentration of total B12, B12 available for cells (holoTC), and methylmalonate (MMA).	Baseline, 6, 12 and 18 months

Collaborators and Investigators

• Sponsor: Bispebjerg Hospital
• Collaborators: University of Copenhagen; Arla Foods
• Investigators: Principal Investigator: Rasmus Bechshøft, Ph.d. stud, Bispebjerg Hospital; Principal Investigator: Michael Kjaer, MD, Proff., Bispebjerg Hospital; Principal Investigator: Søren Reitelseder, Ph.d., Bispebjerg Hospital

Publications and helpful links

General Publications

• Mertz KH, Reitelseder S, Bechshoeft R, Bulow J, Hojfeldt G, Jensen M, Schacht SR, Lind MV, Rasmussen MA, Mikkelsen UR, Tetens I, Engelsen SB, Nielsen DS, Jespersen AP, Holm L. The effect of daily protein supplementation, with or without resistance training for 1 year, on muscle size, strength, and function in healthy older adults: A randomized controlled trial. Am J Clin Nutr. 2021 Apr 6;113(4):790-800. doi: 10.1093/ajcn/nqaa372.
• Bechshoft RL, Reitelseder S, Hojfeldt G, Castro-Mejia JL, Khakimov B, Ahmad HF, Kjaer M, Engelsen SB, Johansen SM, Rasmussen MA, Lassen AJ, Jensen T, Beyer N, Serena A, Perez-Cueto FJ, Nielsen DS, Jespersen AP, Holm L. Counteracting Age-related Loss of Skeletal Muscle Mass: a clinical and ethnological trial on the role of protein supplementation and training load (CALM Intervention Study): study protocol for a randomized controlled trial. Trials. 2016 Aug 9;17(1):397. doi: 10.1186/s13063-016-1512-0.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 10, 2014
• Primary Completion (ACTUAL): June 1, 2019
• Study Completion (ACTUAL): August 1, 2019

Study Registration Dates

• First Submitted: January 10, 2014
• First Submitted That Met QC Criteria: January 10, 2014
• First Posted (ESTIMATE): January 13, 2014

Study Record Updates

• Last Update Posted (ACTUAL): November 29, 2019
• Last Update Submitted That Met QC Criteria: November 27, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Ageing; Sarcopenia; Gut microbiota; Exercise training; Frailty; Protein supplementation; Metabolome; Protein quality
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Muscular Atrophy; Atrophy; Sarcopenia
• Other Study ID Numbers: H-4-2013-070 (OTHER: The Danish National Committee on Biomedical Research Ethics)