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The Granheim COPD Study - Vitamin D and Strength Training

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ClinicalTrials.gov Identifier: NCT02598830
Recruitment Status : Completed
First Posted : November 6, 2015
Last Update Posted : December 12, 2018
Sponsor:
Collaborators:
Sykehuset Innlandet HF
Lillehammer Hospital for Rheumatic Diseases
University of Bergen
University of Copenhagen
Norwegian School of Sport Sciences
Information provided by (Responsible Party):
Inland Norway University of Applied Sciences

Brief Summary:
This study evaluates the effect of vitamin D supplementation on outcomes of 10 weeks progressive strength training in 100 ageing subjects (>45 years of age). Participants will be recruited into two similarly sized strata; one containing COPD patients and one containing healthy subjects of similar age. In each stratum, half the participants will receive vitamin D supplementation and half the participants will receive placebo

Condition or disease Intervention/treatment Phase
Chronic Obstructive Pulmonary Disease Dietary Supplement: Vitamin D3 Dietary Supplement: Placebo Not Applicable

Detailed Description:

Physical activity is a potent way of relieving some of the adverse morbidities associated with COPD, such as muscle atrophy and reduced muscle quality. It is thus problematic that 20-30% of patients fail to elicit positive adaptations to training. This oddity has been ascribed inherent muscular properties, with potential links to comorbidities such as vitamin D and testosterone deficiency and the nature of the training program. In the present project, a double-blinded RCT will be performed to disclose the functional and biological efficacy of vitamin D supplementation (with concomitant ingestion of 1000 mg Ca2+) on the outcomes of 10 wks strength training in 100 aging individuals with or without COPD. The strength training intervention will be preceded by 3 weeks of progressive introduction to training protocols.

50 COPD patients and 50 healthy subjects will be allocated into two strata and separately randomized into two equally sized supplementation groups; (1) vitamin D3 and (2) placebo. The planned 50:50 ratio between COPD patients and healthy individuals may change, depending on the access to COPD patients. All subjects will perform lower-limb strength-training protocols in a contralateral manner: (leg 1) high-resistance (10 RM) and (leg 2) low-resistance (30 RM). Such a one-limb-at-a-time protocol ensures training that is unconfined by the cardiorespiratory limitations inherent to these patients, and allow comparison of the two training modalities in a manner unconfined by individual variation in exercise adaptability. A pilot study investigating the possible central pulmonary capacity limitation to two-legged strength training exercise in COPD patients will be performed. In this pilot study, we will compare exercise performance involving large and small muscle mass. In addition, all subjects will perform a selection of bilateral upper body exercises (10 RM), ensuring adequate hormonal responses and compliance to the study. The study is likely to revitalize guidelines for rehabilitation of COPD patients, and to provide vital information regarding the role of vitamin D in adaptations to strength training.

For outcome measures specific to COPD pasients, final analyses will be performed on data from the COPD population only. For other outcome measures, final analyses will be performed on data merged from COPD patients and healthy subjects. An important rationale behind implementing healthy control subjects is to increase the statistical power of outcome measures unrelated to COPD epidemiology, which are of general relevance to physiological adaptation to strength training. In a related set of analyses, we will perform between-groups comparisons, including multivariate analyses. We will also compare the efficacy of high- and low-resistance strength training in COPD patients and healthy control subjects. The two training modalities are expected to result in similar muscular adaptations.

In general, baseline vitamin D levels in blood, measured as 25(OH)D, is anticipated to be a determinant of the efficacy of the strength training intervention. In response to vitamin D3 supplementation, individuals with low baseline levels of 25(OH)D are expected to display more pronounced changes in biological active vitamin D, leading to more pronounced changes in functional and biological outcome measures in response to strength training. In contrast, supplementation may not lead to further elevation of blood 25(OH)D levels in individuals with high baseline levels, essentially meaning that vitamin D3 ingestion will be leveled out by or exceeded by the elimination of vitamin D derivatives. In these individuals, vitamin D3 ingestion will not have an additive effect on functional and biological outcome measures in response to strength training. To assess individual variation in vitamin D responses, data on functional and biological variables will be divided into quartiles based on baseline 25(OH)D-levels, whereupon comparisons will be made between low-end and high-end quartiles. Individual variation in responses to vitamin D supplementation and strength training will also be assessed using a mixed model approach.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 97 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Granheim COPD Study: Effects of Vitamin D3-supplementation on the Efficacy of Strength Training in COPD Patients and Healthy Controls - a Double-blinded RCT
Actual Study Start Date : November 2015
Actual Primary Completion Date : June 2018
Actual Study Completion Date : June 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vitamin D

Arm Intervention/treatment
Experimental: Vitamin D3+str.training, COPD & Healthy

Vitamin D3 capsules for 30 weeks:

  • weeks 1-2: 10000 IU/day (equivalent to 250 ug), accompanied by 1000 mg Ca2+
  • weeks 3-30: 2000 IU/day (equivalent to 50 ug), accompanied by 1000 mg Ca2+

Progressive unilateral strength training of the legs for 3+10 weeks (weeks 15-28); leg 1 = high-load training, leg 2 = low-load training, allocated to left and right foot in a randomized manner:

  • weeks 15-17, familiarization period
  • week 18, test period
  • weeks 19-28, intervention period
  • weeks 29-30, test period
Dietary Supplement: Vitamin D3
Vitamin D3 dissolved in olive oil, encapsuled
Other Name: cholecalciferol

Placebo Comparator: Placebo+str.training, COPD & Healthy

Placebo capsules for 30 weeks (the number of capsules ingested each day match those of the vitamin D3 group)

Progressive unilateral strength training of the legs for 3+10 weeks (weeks 15-28); leg 1 = high-load training, leg 2 = low-load training, allocated to left and right foot in a randomized manner:

  • weeks 15-17, familiarization period
  • week 18, test period
  • weeks 19-28, intervention period
  • weeks 29-30, test period
Dietary Supplement: Placebo
Olive oil, encapsuled




Primary Outcome Measures :
  1. Muscle size [ Time Frame: Changes from before to after the strength training intervention (week 19 to week 28) ]
    Muscle cell cross-sectional area measured in biopsies from m. vastus lateralis using immunohistochemistry

  2. Muscle phenotype [ Time Frame: Changes from before to after the strength training intervention (week 19 to week 28) ]
    Muscle fiber type composition measured in biopsies from m. vastus lateralis using immunohistochemistry


Secondary Outcome Measures :
  1. Lung function [ Time Frame: Changes from before to after the strength training intervention (week 19 to week 28) ]
    Lung function measured using spirometry

  2. One-legged cycling [ Time Frame: Changes from before to after the strength training intervention (week 19 to week 28) ]
    Performance indicies measured during an incremental one-legged cycling test

  3. Hormones in blood [ Time Frame: Changes over the course of the intervention (week 0 to 28) ]
    Levels of hormones in blood

  4. Cytokines in blood [ Time Frame: Changes over the course of the intervention (week 0 to 28) ]
    Levels of cytokines in blood

  5. Steroids in skeletal muscle [ Time Frame: Changes over the course of the intervention (week 0 to 28) ]
    Levels of steroids in m. vastus lateralis

  6. Androgen-converting enzymes in skeletal muscle [ Time Frame: Changes from before to after the strength training intervention (week 19 to week 28) ]
    Levels of androgen-converting enzymes in m. vastus lateralis

  7. Gene expression in skeletal muscle [ Time Frame: Changes from before to after the strength training intervention (week 19 to week 28) ]
    RNA (e.g. messenger RNA, ribosomal RNA, microRNA, long non-coding RNA) abundances in m. vastus lateralis, measured both as single genes and at the level of the transcriptome

  8. Gene expression in skeletal muscle [ Time Frame: Changes from before to after familiarization to strength training (week 15 to week 17) ]
    RNA (e.g. messenger RNA, ribosomal RNA, microRNA, long non-coding RNA) abundances in m. vastus lateralis, measured both as single genes and at the level of the transcriptome

  9. Protein abundances in skeletal muscle [ Time Frame: Changes from before to after the strength training intervention (week 19 to week 28) ]
    Levels of proteins and their modification status (e.g. phosphorylation) in m. vastus lateralis, measured at the level of single proteins and at the level of the proteome

  10. Protein abundances in skeletal muscle [ Time Frame: Changes from before to after familiarization to strength training (week 15 to week 17) ]
    Levels of proteins and their modification status (e.g. phosphorylation) in m. vastus lateralis, measured at the level of single proteins and at the level of the proteome

  11. Vitamin D in blood [ Time Frame: Changes over the course of the intervention (week 0 to 28) ]
    Levels of vitamin D in blood

  12. Step test [ Time Frame: Changes from before to after the strength training intervention (week 19 to week 28) ]
    Performance and performance indicies measured during a 6 minutes step test

  13. Pasient-reported outcome measures, generic [ Time Frame: Changes from before to after the strength training intervention (week 19 to week 28) ]
    Pasient-related outcome measures assessed using the generic survey SF-36

  14. Pasient-reported outcome measures, COPD-specific [ Time Frame: Changes from before to after the strength training intervention (week 19 to week 28) ]
    COPD-specific pasient-reported outcome assessed using COPD assessment test

  15. Body mass composition [ Time Frame: Changes from before to after the strength training intervention (week 19 to week 28) ]
    Body mass composition measured using Dual-energy X-ray absorptiometry (DXA)

  16. Bilateral upper body maximal strength [ Time Frame: Changes from before to after the strength training intervention (week 19 to week 28) ]
    The ability of muscles of the upper body to exert maximal force during dynamic movements

  17. Grip strength [ Time Frame: Changes from before to after the strength training intervention (week 19 to week 28) ]
    Isometric hand grip strength

  18. Sit-to-stand test [ Time Frame: Changes from before to after the strength training intervention (week 19 to week 28) ]
    Performance and performance indicies measured during a sit-to-stand test

  19. Unilateral lower body maximal muscle strength [ Time Frame: Changes from before to after the strength training intervention (week 19 to week 28) ]
    The ability of muscles of the lower body to exert maximal force during dynamic movements

  20. Unilateral lower body muscle endurance [ Time Frame: Changes from before to after the strength training intervention (week 19 to week 28) ]
    The ability of muscles of the lower body to perform repeated dynamic contractions at a specified submaximal load to exhaustion

  21. Bilateral upper body muscle endurance [ Time Frame: Changes from before to after the strength training intervention (week 19 to week 28) ]
    The ability of muscles of the upper body to perform repeated dynamic contractions at a specified submaximal load to exhaustion

  22. Unilateral lower body isokinetic muscle strength [ Time Frame: Changes from before to after the strength training intervention (week 19 to week 28) ]
    The ability of muscles of the lower body to exert maximal force during isokinetic movements

  23. Daily life activity level [ Time Frame: Changes from before to after the intervention (week 0 to week 28) ]
    Daily life activity level measured using accelerometer

  24. Muscle cell biological traits [ Time Frame: Changes from before to after the strength training intervention (week 19 to week 28) ]
    Muscle cell biological traits, including numbers of myonuclei, satelitte cells and capillaries, measured in biopsies from m. vastus lateralis using immunohistochemistry

  25. Muscle mitochondrial quantities [ Time Frame: Changes from before to after the strength training intervention (week 19 to week 28) ]
    Mitochondrial quantities measured in biopsies from m. vastus lateralis

  26. Muscle mitochondrial functions [ Time Frame: Changes from before to after the strength training intervention (week 19 to week 28) ]
    Mitochondrial functions measured in biopsies from m. vastus lateralis


Other Outcome Measures:
  1. Training diary [ Time Frame: Measured over the course of the strength training familiarization period and the strength training intervention (week 15 to week 28) ]
    Training diary containing information about type of training, duration of training and training intensity

  2. Dietary registration [ Time Frame: Registred at one time point during the strength training intervention (~week 23, registred over four days) ]
    Detailed registration of food intake

  3. Self-reported information on lifestyle-related aspects [ Time Frame: Measured over the course of the intervention (week 0 to week 28) ]
    Disease, symptoms, injury, vitamin D-intake, time spent outdoors, solarium, training background, smoking, etc



Information from the National Library of Medicine

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Ages Eligible for Study:   45 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

COPD group

Inclusion Criteria:

  • Stable COPD at GOLD stage II or III, FEV1/FVC < 0.7 and FEV1 <80% and >30% of predicted
  • >45 years of age

Exclusion Criteria:

  • Unstable cardiovascular disease
  • Chronic granulomatous
  • Known active malignant disease within last 5 years
  • Physically disabling muscloskeletal diseases
  • Peroral use of steroids within last 2 months
  • Serious psychiatric comorbidity
  • Less than 4 weeks since last return t o habit ual condit ion from exacerbation
  • Failing to understand Norwegian literary or verbally
  • Medical record diagnosis of asthma
  • More than one bout of strength training per week during the last 6 months leading up to the project

Healthy control group

Inclusion Criteria:

- >45 years of age

Exclusion Criteria:

  • COPD
  • Unstable cardiovascular disease
  • Chronic granulomatous
  • Known active malignant disease within last 5 years
  • Physically disabling muscloskeletal diseases
  • Peroral use of steroids within last 2 months
  • Serious psychiatric comorbidity
  • Failing to understand Norwegian literary or verbally
  • Medical record diagnosis of asthma
  • More than one bout of strength training per week during the last 6 months leading up to the project

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02598830


Locations
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Norway
Inland Norway University of Applied Sciences
Lillehammer, Norway
Sponsors and Collaborators
Inland Norway University of Applied Sciences
Sykehuset Innlandet HF
Lillehammer Hospital for Rheumatic Diseases
University of Bergen
University of Copenhagen
Norwegian School of Sport Sciences
Investigators
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Principal Investigator: Knut Sindre Mølmen, MSc Inland Norway University of Applied Sciences

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Responsible Party: Inland Norway University of Applied Sciences
ClinicalTrials.gov Identifier: NCT02598830     History of Changes
Other Study ID Numbers: Trainsome 2014#004
First Posted: November 6, 2015    Key Record Dates
Last Update Posted: December 12, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified data will be made available to the academic community through the general biobank "The Trainsome - effects of exercise and environment on human cells" (REK-2013/2045, Regional Comitees for Medical and Health Research Ethics South East). Data will be available on request and will be restricted to scientists and/or projects with a sound scientific purpose and rationale.
Keywords provided by Inland Norway University of Applied Sciences:
Cachexia
Vitamin D
Muscle
Strength training
Additional relevant MeSH terms:
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Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Lung Diseases
Respiratory Tract Diseases
Vitamin D
Ergocalciferols
Cholecalciferol
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents
Calcium-Regulating Hormones and Agents