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SarcopeniaNCT03326648

The Role of Muscle Protein Breakdown in the Regulation of Muscle Quality in Frail Elderly Individuals

A study testing Strength training and Protein supplementation in people with Sarcopenia, run by Truls Raastad at 1 site in Norway.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to investigate mechanisms underlying the reduction in muscle quality (the ratio between muscle strength and muscle size) with aging, and to investigate how these factors are affected by strength training and protein supplementation. Read more about this study

Who is it for?
Ages 65 years and olderHealthy volunteers can take part
Conditions the study is for
Sarcopenia
What is being tested?
Strength training and Protein supplementation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
34 participants
Where
1 siteNorway
Study dates
1 Sep 2016to 1 Mar 2018
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 65 years and older
  • All sexes
  • Healthy volunteers accepted
  • Older adult

Who may be able to join

  • Age > 65
  • Frail or pre-frail according to the Fried Frailty Criteria or Short Physical Performance Battery (SPPB) score <6.
  • Mini Mental State Examination score > 18

Who cannot join

  • Diseases or injuries contraindicating participation
  • Lactose intolerance
  • Allergy to milk
  • Allergy towards local anesthetics (xylocain)
  • Use of anticoagulants that cannot be discontinued prior to the muscle biopsy

Trial locations and contacts

1 site in 1 country.

Norway1 site
  • Norwegian School of Sport Sciences

    Oslo, 0863

Other trials in Norway

About this study

The purpose of this study is to investigate mechanisms underlying the reduction in muscle quality (the ratio between muscle strength and muscle size) with aging, and to investigate how these factors are affected by strength training and protein supplementation. It is already established that muscle quality defined as the ratio between the strength and the size of a muscle is improved with strength training, even in frail elderly individuals. However, the relative contribution of factors such as activation level, fat infiltration, muscle architecture and single fiber function is unknown. The main focus of this study is to investigate the relationship between muscle quality and muscle protein breakdown, as insufficient degradation of proteins is hypothesized to negatively affect muscle quality.

Read the detailed description

Aging is associated with impaired skeletal muscle function. This is evident not only by a reduced capacity to generate force and power at the whole muscle level, but also by a decline in individual muscle fiber contraction velocity and force generation. Combined with muscle atrophy, these changes lead to reduced muscle strength and quality and loss off physical function with age. Clinically, muscle quality may be a better indicator of overall functional capacity than absolute muscle strength. Thus, identifying the mechanisms underlying the age-related loss of muscle quality is of high relevance for the prevention of functional impairment with aging. The explanation for the loss of muscle quality with aging seems to be multifactorial, with alterations in voluntary muscle activation, muscle architecture, fat infiltration and impaired contractile properties of single muscle fibers being likely contributors. Single fiber specific force seems to be related to myosin heavy chain (MHC) content, which is thought to reflect the number of available cross-bridges. The reduction of single fiber specific force with aging may thus be a consequence of reduced synthesis of MHC and/or increased concentration of non-contractile tissue (e.g. intramyocellular lipids).

Some studies in mice also indicate attenuated activity in some of the pathways responsible for degradation of muscle proteins with aging (especially autophagy). As a result, damaged proteins and organelles are not removed as effectively as they should, which could ultimately compromise the muscle's ability to produce force. In addition, reduced efficiency of mitophagy and lipophagy (two specific forms of autophagy), may indirectly affect single fiber specific force, through oxidative damage by reactive oxygen species (ROS) and increased levels of intramyocellular lipids, respectively. Although animal studies indicate attenuated autophagic function, exercise seems to restore the activity in this pathway. Whether this also is the case in humans is unknown. Thus, the purpose of this study is to investigate how the different factors contributing to reduced muscle quality in frail elderly individuals, with emphasis on the relationship between muscle quality and autophagy, may be counteracted by a specific strength training program targeting muscle quality and muscle mass.

In this randomized controlled trial the investigators will aim to recruit frail elderly individuals, as muscle quality is shown to be low in this population. As a consequence, the potential for improved muscle quality is expected to be large. Subjects will be randomized to two groups; one group performing strength training twice a week for 10 weeks in addition to receiving daily protein supplementation. The other group will only receive the protein supplement. Several tests will be performed before and after the intervention period, including a test day where a biopsy is obtained both at rest, and 2.5 hours following strength training + protein supplementation or protein supplementation only. This will provide information about the regulation of muscle protein breakdown in a resting state, following protein intake and following strength training in combination with protein intake. As this will be done both before and after the training period, it will also provide information on how long-term strength training affects the activity in these systems.

Conditions
Sarcopenia
Being tested
Strength training, Protein supplementation
Keywords
Sarcopenia, Frailty, Strength training, Autophagy
Medical subject headings
Sarcopenia, Frailty

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Strength trainingOther

    Also called Resistance training

    Heavy load strength training performed twice a week for 10 weeks.

  • Protein supplementationDietary supplement

    Dietary protein supplement (protein-enriched milk with 0,2 % fat). 0,33 l each day for 10 weeks.

Study groups in NCT03326648
Study groupRoleWhat they receive
Strength training + protein supplementExperimentalTwo sessions of strength training each week in addition to daily protein supplementation for 10 weeks.
Receives: Other: Strength training; Dietary Supplement: Protein supplementation
Protein supplementExperimentalDaily protein supplementation for 10 weeks.
Receives: Dietary Supplement: Protein supplementation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Single fiber specific force

    A measure of muscle quality at the single fiber level. Biopsies obtained from m. Vastus Lateralis

    Measured: Change from baseline at 10 weeks

Secondary outcomes (51)
  1. Lean mass

    Measured by a Dual-energy X-ray absorptiometry (DXA) scan

    Measured: Change from baseline at 10 weeks

  2. Fat mass

    Measured by a Dual-energy X-ray absorptiometry (DXA) scan

    Measured: Change from baseline at 10 weeks

  3. Bone mineral density

    Measured by a Dual-energy X-ray absorptiometry (DXA) scan

    Measured: Change from baseline at 10 weeks

  4. Muscle strength of m. quadriceps

    Maximal isometric and dynamic muscle strength of m. quadriceps

    Measured: Change from baseline at 10 weeks

  5. Muscle size of m. quadriceps

    Cross-sectional area of m. quadriceps measured by a Computed Tomography scan

    Measured: Change from baseline at 10 weeks

  6. Fat infiltration of m. quadriceps

    Fat infiltration of m. quadriceps measured by a Computed Tomography scan

    Measured: Change from baseline at 10 weeks

  7. Muscle activation

    Voluntary activation level during a maximal isometric knee extension using the interpolated twitch technique

    Measured: Change from baseline at 10 weeks

  8. Fractional Breakdown Rate

    Measurement of fractional breakdown rate by the use of orally provided Deuterium Oxide, biopsies and blood samples

    Measured: Measured over the last 14 days of the intervention period

  9. m. Vastus Lateralis thickness

    Measured by ultrasound

    Measured: Change from baseline at 10 weeks

  10. Chair stand performance

    Time (sec) to stand up from a chair five times

    Measured: Change from baseline at 10 weeks

  11. Habitual gait velocity

    Time (sec) to walk 6 meters at habitual gait velocity

    Measured: Change from baseline at 10 weeks

  12. Maximal gait velocity

    Time (sec) to walk 6 meters as fast as possible

    Measured: Change from baseline at 10 weeks

  13. Level/cellular location of Microtubule-associated protein 1A/1B-light chain 3 (LC3)

    Biopsies from m. Vastus Lateralis analyzed by western blot

    Measured: Before and 2.5 hours after acute training session both at baseline and after 10 weeks

  14. Level/cellular location of p62/Sequestosome-1

    Biopsies from m. Vastus Lateralis analyzed by western blot

    Measured: Before and 2.5 hours after acute training session both at baseline and after 10 weeks

  15. Level/cellular location of Lysosome-associated membrane glycoprotein 2 (LAMP2)

    Biopsies from m. Vastus Lateralis analyzed by western blot

    Measured: Before and 2.5 hours after acute training session both at baseline and after 10 weeks

  16. Level/cellular location of forkhead box O3 (FOXO3a)

    Biopsies from m. Vastus Lateralis analyzed by western blot

    Measured: Before and 2.5 hours after acute training session both at baseline and after 10 weeks

  17. Phosphorylation status and total level of ribosomal protein S6 kinase beta-1(P70S6K)

    Biopsies from m. Vastus Lateralis analyzed by western blot

    Measured: Before and 2.5 hours after acute training session both at baseline and after 10 weeks

  18. Phosphorylation status and total level of eukaryotic elongation factor 2 (eEF-2)

    Biopsies from m. Vastus Lateralis analyzed by western blot

    Measured: Before and 2.5 hours after acute training session both at baseline and after 10 weeks

  19. Phosphorylation status and total level of eukaryotic translation initiation factor 4E-binding protein 1 (4EBP-1)

    Biopsies from m. Vastus Lateralis analyzed by western blot

    Measured: Before and 2.5 hours after acute training session both at baseline and after 10 weeks

  20. Level/cellular location of muscle RING-finger protein-1 (Murf-1)

    Biopsies from m. Vastus Lateralis analyzed by western blot

    Measured: Before and 2.5 hours after acute training session both at baseline and after 10 weeks

  21. Level/cellular location of ubiquitin (Ub)

    Biopsies from m. Vastus Lateralis analyzed by western blot

    Measured: Before and 2.5 hours after acute training session both at baseline and after 10 weeks

  22. Blood serum glucose

    Fasted

    Measured: Change from baseline at 10 weeks

  23. Blood serum insulin

    Fasted

    Measured: Change from baseline at 10 weeks

  24. Blood plasma Hemoglobin A1c (HbA1c)

    Fasted

    Measured: Change from baseline at 10 weeks

  25. Blood serum Triglycerides

    Fasted

    Measured: Change from baseline at 10 weeks

  26. Blood serum High-density lipoproteins (HDL)

    Fasted

    Measured: Change from baseline at 10 weeks

  27. Blood serum Low-density lipoproteins (LDL)

    Fasted

    Measured: Change from baseline at 10 weeks

  28. Blood serum C-reactive protein (CRP)

    Fasted

    Measured: Change from baseline at 10 weeks

  29. forkhead box protein O3 (FOXO3A) mRNA

    Biopsies from m. Vastus Lateralis analyzed by western blot

    Measured: Before and 2.5 hours after acute training session both at baseline and after 10 weeks

  30. forkhead box protein O1 (FOXO1) mRNA mRNA

    Biopsies from m. Vastus Lateralis analyzed by western blot

    Measured: Before and 2.5 hours after acute training session both at baseline and after 10 weeks

  31. hepatocyte growth factor (HGF) mRNA

    Biopsies from m. Vastus Lateralis analyzed by western blot

    Measured: Before and 2.5 hours after acute training session both at baseline and after 10 weeks

  32. insulin-like growth factor I (IGF1) mRNA

    Biopsies from m. Vastus Lateralis analyzed by western blot

    Measured: Before and 2.5 hours after acute training session both at baseline and after 10 weeks

  33. myostatin (MSTN) mRNA

    Biopsies from m. Vastus Lateralis analyzed by western blot

    Measured: Before and 2.5 hours after acute training session both at baseline and after 10 weeks

  34. E3 ubiquitin-protein ligase TRIM63 (TRIM63) mRNA

    Biopsies from m. Vastus Lateralis analyzed by western blot

    Measured: Before and 2.5 hours after acute training session both at baseline and after 10 weeks

  35. p62/Sequestosome-1 mRNA

    Biopsies from m. Vastus Lateralis analyzed by western blot

    Measured: Before and 2.5 hours after acute training session both at baseline and after 10 weeks

  36. muscle RING-finger protein-1 (Murf-1) protein 1 (4EBP-1) mRNA

    Biopsies from m. Vastus Lateralis analyzed by western blot

    Measured: Before and 2.5 hours after acute training session both at baseline and after 10 weeks

  37. Atrogin1 mRNA

    Biopsies from m. Vastus Lateralis analyzed by western blot

    Measured: Before and 2.5 hours after acute training session both at baseline and after 10 weeks

  38. Microtubule-associated protein 1A/1B-light chain 3 (LC3) mRNA

    Biopsies from m. Vastus Lateralis analyzed by western blot

    Measured: Before and 2.5 hours after acute training session both at baseline and after 10 weeks

  39. BCL2/adenovirus E1B interacting protein 3 (BNIP3) mRNA

    Biopsies from m. Vastus Lateralis analyzed by western blot

    Measured: Before and 2.5 hours after acute training session both at baseline and after 10 weeks

  40. PTEN-induced putative kinase 1 (PINK1) mRNA

    Biopsies from m. Vastus Lateralis analyzed by western blot

    Measured: Before and 2.5 hours after acute training session both at baseline and after 10 weeks

  41. TNF receptor associated factor 6 (TRAF6) mRNA

    Biopsies from m. Vastus Lateralis analyzed by western blot

    Measured: Before and 2.5 hours after acute training session both at baseline and after 10 weeks

  42. transcription factor EB (Tfeb) mRNA

    Biopsies from m. Vastus Lateralis analyzed by western blot

    Measured: Before and 2.5 hours after acute training session both at baseline and after 10 weeks

  43. Intramyocellular lipids

    Oil-Red-O staining of muscle sections. Biopsy from m. Vastus Lateralis analyzed by immunohistochemistry

    Measured: Change from baseline at 10 weeks

  44. Muscle fiber type distribution

    Biopsy from m. Vastus Lateralis analyzed by immunohistochemistry

    Measured: Change from baseline at 10 weeks

  45. Muscle fiber cross-sectional area

    Biopsy from m. Vastus Lateralis analyzed by immunohistochemistry

    Measured: Change from baseline at 10 weeks

  46. Muscle satellite cells

    Biopsy from m. Vastus Lateralis analyzed by immunohistochemistry

    Measured: Change from baseline at 10 weeks

  47. Myonuclei

    Biopsy from m. Vastus Lateralis analyzed by immunohistochemistry

    Measured: Change from baseline at 10 weeks

  48. Myonuclei number

    Biopsy from m. Vastus Lateralis analyzed by confocal microscopy

    Measured: Change from baseline at 10 weeks

  49. Myonuclei location

    Biopsy from m. Vastus Lateralis analyzed by confocal microscopy

    Measured: Change from baseline at 10 weeks

  50. Amount of mitochondria

    Biopsy from m. Vastus Lateralis analyzed by confocal microscopy

    Measured: Change from baseline at 10 weeks

  51. Location of mitochondria

    Biopsy from m. Vastus Lateralis analyzed by confocal microscopy

    Measured: Change from baseline at 10 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Oct 2017
  2. Study start1 Sep 2016
  3. Primary completion20 Dec 2017
  4. Study completion1 Mar 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
34 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03326648
Sponsor's protocol ID
STAS
Status last verified
Apr 2018
First submitted
5 May 2017
Last updated
11 Apr 2018
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A study testing Strength training and Protein supplementation in people with Sarcopenia, run by Truls Raastad at 1 site in Norway.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Single fiber specific force (time frame: Change from baseline at 10 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Apr 2018.

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