Back to resultsCounteracting Age-related Loss of Skeletal Muscle Mass (CALM)
Primary Purpose
Sarcopenia, Muscle Loss
Status
Completed
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Heavy Resistance Training
Light Intensity Training
Protein Whey
Protein Collagen
Carbohydrate
Sponsored by
About this trial
This is an interventional prevention trial for Sarcopenia focused on measuring Frailty, Ageing, Protein supplementation, Protein quality, Gut microbiota, Metabolome, Exercise training, Sarcopenia
Eligibility Criteria
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.
Sites / Locations
- Bispbebjerg Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Active Comparator
Experimental
Active Comparator
Active Comparator
Placebo Comparator
Arm Label
Heavy Resistance Training
Light Intensity Training
Protein Whey
Protein Collagen
Carbohydrate
Arm Description
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.
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.
Two daily 20g whey protein and 10g carbohydrate supplementations for 52 weeks.
Two daily 20g collagen protein and 10g carbohydrate supplementations for 52 weeks.
Two daily 30g carbohydrate supplementations for 52 weeks.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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).
Change in quadriceps muscle isokinetic strength
Unilateral knee extension (concentric) strength measured in the KinCom device at an angular velocity of 60 degrees/sec.
Change in leg extension muscle power
Unilateral leg extension power measured in the Powerrig device.
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.
Change in gut microbiota composition.
Molecular biology based methods incl. high throughput sequencing aided by classical, culture-based microbiological techniques as needed.
Change in faecal metabolome.
NMR of faecal samples.
Change in faecal metabolome.
Gas chromatography mass spectrometry (GCMS) of faecal samples.
Change in plasma metabolome.
Nuclear magnetic resonance (NMR) of plasma samples.
Change in plasma metabolome.
GCMS of plasma samples.
Change in 30 s chair stand
Number of stand-ups from a chair in 30 seconds.
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.
Full Information
NCT ID
NCT02034760
First Posted
January 10, 2014
Last Updated
November 27, 2019
Sponsor
Bispebjerg Hospital
Collaborators
University of Copenhagen, Arla Foods
1. Study Identification
Unique Protocol Identification Number
NCT02034760
Brief Title
Counteracting Age-related Loss of Skeletal Muscle Mass
Acronym
CALM
Official Title
Counteracting Age-related Loss of Skeletal Muscle Mass
Study Type
Interventional
2. Study Status
Record Verification Date
November 2019
Overall Recruitment Status
Completed
Study Start Date
January 10, 2014 (Actual)
Primary Completion Date
June 2019 (Actual)
Study Completion Date
August 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Bispebjerg Hospital
Collaborators
University of Copenhagen, Arla Foods
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sarcopenia, Muscle Loss
Keywords
Frailty, Ageing, Protein supplementation, Protein quality, Gut microbiota, Metabolome, Exercise training, Sarcopenia
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
InvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
208 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Heavy Resistance Training
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Light Intensity Training
Arm Type
Experimental
Arm Description
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.
Arm Title
Protein Whey
Arm Type
Active Comparator
Arm Description
Two daily 20g whey protein and 10g carbohydrate supplementations for 52 weeks.
Arm Title
Protein Collagen
Arm Type
Active Comparator
Arm Description
Two daily 20g collagen protein and 10g carbohydrate supplementations for 52 weeks.
Arm Title
Carbohydrate
Arm Type
Placebo Comparator
Arm Description
Two daily 30g carbohydrate supplementations for 52 weeks.
Intervention Type
Procedure
Intervention Name(s)
Heavy Resistance Training
Intervention Description
Supervised Heavy Resistance Training three times weekly for 52 weeks.
Intervention Type
Procedure
Intervention Name(s)
Light Intensity Training
Intervention Description
Home-based Light Intensity Training three-five times weekly for 52 weeks.
Intervention Type
Dietary Supplement
Intervention Name(s)
Protein Whey
Intervention Description
Two daily 20g whey protein and 10g carbohydrate supplementations for 52 weeks.
Intervention Type
Dietary Supplement
Intervention Name(s)
Protein Collagen
Intervention Description
Two daily 20g collagen protein and 10g carbohydrate supplementations for 52 weeks.
Intervention Type
Dietary Supplement
Intervention Name(s)
Carbohydrate
Intervention Description
Two daily 30g carbohydrate supplementations for 52 weeks.
Primary Outcome Measure Information:
Title
Change in muscle cross sectional area
Description
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.
Time Frame
Baseline, 6, 12, and 18 months
Secondary Outcome Measure Information:
Title
Change in quadriceps muscle isometric strength
Description
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).
Time Frame
Baseline, 6, 12 and 18 months
Title
Change in quadriceps muscle isokinetic strength
Description
Unilateral knee extension (concentric) strength measured in the KinCom device at an angular velocity of 60 degrees/sec.
Time Frame
Baseline, 6, 12 and 18 months
Title
Change in leg extension muscle power
Description
Unilateral leg extension power measured in the Powerrig device.
Time Frame
Baseline, 6, 12 and 18 months
Title
Change from baseline in muscle structure and signalling
Description
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.
Time Frame
Baseline and 12 months
Title
Change in gut microbiota composition.
Description
Molecular biology based methods incl. high throughput sequencing aided by classical, culture-based microbiological techniques as needed.
Time Frame
Baseline, 6 and 12 months (and 18 months on a subset of samples).
Title
Change in faecal metabolome.
Description
NMR of faecal samples.
Time Frame
Baseline, 6 and 12 months (and 18 months on a subset of samples).
Title
Change in faecal metabolome.
Description
Gas chromatography mass spectrometry (GCMS) of faecal samples.
Time Frame
Baseline, 6 and 12 months (and 18 months on a subset of samples).
Title
Change in plasma metabolome.
Description
Nuclear magnetic resonance (NMR) of plasma samples.
Time Frame
Baseline, 6 and 12 months (and 18 months on a subset of samples).
Title
Change in plasma metabolome.
Description
GCMS of plasma samples.
Time Frame
Baseline, 6 and 12 months (and 18 months on a subset of samples).
Title
Change in 30 s chair stand
Description
Number of stand-ups from a chair in 30 seconds.
Time Frame
Baseline, 6, 12 and 18 months
Title
Change in whole body composition and bone mineral density
Description
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.
Time Frame
Baseline, 6, 12 and 18 months
Other Pre-specified Outcome Measures:
Title
Change in blood parameters and anthropometry
Description
Blood: HbA1c, plasma lipids, vitamin B12 and related metabolites. Anthropometry: Weight, abdominal circumference. Blood pressure.
Time Frame
Baseline, 6, 12 and 18 months
Title
Change in gait speed
Description
400 m gait speed.
Time Frame
Baseline, 6, 12 and 18 months
Title
Change in grip strength
Description
Isometric hand grip strength.
Time Frame
Baseline, 6, 12 and 18 months
Title
Change in tendon biomechanical properties
Description
Measurements of tendon biomechanical properties.
Time Frame
Baseline and 12 months
Title
Questionnaires and interviews
Description
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.
Time Frame
Baseline and 12 months
Title
Change in daily macronutrient intake
Description
3-days self-report of food and beverage intake.
Time Frame
Baseline, 1.5/2 and 12 months
Title
Change in habitual activity
Description
Evaluated by 4 days continuous monitoring by a pedometer device (ActivPal).
Time Frame
Baseline, 6, 12 and 18 months
Title
Questionnaire on acceptance of supplements
Description
Questionnaires on acceptance of supplementation
Time Frame
Weekly for first 3 months and every 3rd month until 12 months
Title
Change in glucose handling measured by a OGTT
Description
Completion of an oral glucose tolerance test (OGTT)
Time Frame
Baseline and 12 months
Title
Change in vitamin B12 and related metabolite concentrations in blood
Description
Concentration of total B12, B12 available for cells (holoTC), and methylmalonate (MMA).
Time Frame
Baseline, 6, 12 and 18 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rasmus Bechshøft, Ph.d. stud
Organizational Affiliation
Bispebjerg Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Lars Holm, Assoc. prof.
Organizational Affiliation
Bispebjerg Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Michael Kjaer, MD, Proff.
Organizational Affiliation
Bispebjerg Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Søren Reitelseder, Ph.d.
Organizational Affiliation
Bispebjerg Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jacob Bülow, MD PhD stud
Organizational Affiliation
Bispebjerg Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Bispbebjerg Hospital
City
Copenhagen NV
ZIP/Postal Code
2400
Country
Denmark
12. IPD Sharing Statement
Citations:
PubMed Identifier
33564844
Citation
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.
Results Reference
derived
PubMed Identifier
27507236
Citation
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.
Results Reference
derived
Learn more about this trial
Counteracting Age-related Loss of Skeletal Muscle Mass
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