Clinical trial NCT02598830: The Granheim COPD Study - Vitamin D and Strength Training
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: Cachexia
Vitamin D
Muscle
Strength training
Lead sponsor: Inland Norway University of Applied Sciences
Sponsor class: OTHER
Collaborators: name: Sykehuset Innlandet HF
name: Lillehammer Hospital for Rheumatic Diseases
name: University of Bergen
name: University of Copenhagen
name: Norwegian School of Sport Sciences
First posted: 2015-11-06
Enrollment: 97
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility 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

Primary outcomes:
measure: Muscle size
timeFrame: Changes from before to after the strength training intervention (week 19 to week 28)
measure: Muscle phenotype
timeFrame: Changes from before to after the strength training intervention (week 19 to week 28)
Secondary outcomes:
measure: Lung function
timeFrame: Changes from before to after the strength training intervention (week 19 to week 28)
measure: One-legged cycling
timeFrame: Changes from before to after the strength training intervention (week 19 to week 28)
measure: Hormones in blood
timeFrame: Changes over the course of the intervention (week 0 to 28)
measure: Cytokines in blood
timeFrame: Changes over the course of the intervention (week 0 to 28)
measure: Steroids in skeletal muscle
timeFrame: Changes over the course of the intervention (week 0 to 28)
measure: Androgen-converting enzymes in skeletal muscle
timeFrame: Changes from before to after the strength training intervention (week 19 to week 28)
measure: Gene expression in skeletal muscle
timeFrame: Changes from before to after the strength training intervention (week 19 to week 28)
measure: Gene expression in skeletal muscle
timeFrame: Changes from before to after familiarization to strength training (week 15 to week 17)
measure: Protein abundances in skeletal muscle
timeFrame: Changes from before to after the strength training intervention (week 19 to week 28)
measure: Protein abundances in skeletal muscle
timeFrame: Changes from before to after familiarization to strength training (week 15 to week 17)
measure: Vitamin D in blood
timeFrame: Changes over the course of the intervention (week 0 to 28)
measure: Step test
timeFrame: Changes from before to after the strength training intervention (week 19 to week 28)
measure: Pasient-reported outcome measures, generic
timeFrame: Changes from before to after the strength training intervention (week 19 to week 28)
measure: Pasient-reported outcome measures, COPD-specific
timeFrame: Changes from before to after the strength training intervention (week 19 to week 28)
measure: Body mass composition
timeFrame: Changes from before to after the strength training intervention (week 19 to week 28)
measure: Bilateral upper body maximal strength
timeFrame: Changes from before to after the strength training intervention (week 19 to week 28)
measure: Grip strength
timeFrame: Changes from before to after the strength training intervention (week 19 to week 28)
measure: Sit-to-stand test
timeFrame: Changes from before to after the strength training intervention (week 19 to week 28)
measure: Unilateral lower body maximal muscle strength
timeFrame: Changes from before to after the strength training intervention (week 19 to week 28)
measure: Unilateral lower body muscle endurance
timeFrame: Changes from before to after the strength training intervention (week 19 to week 28)
measure: Bilateral upper body muscle endurance
timeFrame: Changes from before to after the strength training intervention (week 19 to week 28)
measure: Unilateral lower body isokinetic muscle strength
timeFrame: Changes from before to after the strength training intervention (week 19 to week 28)
measure: Daily life activity level
timeFrame: Changes from before to after the intervention (week 0 to week 28)
measure: Muscle cell biological traits
timeFrame: Changes from before to after the strength training intervention (week 19 to week 28)
measure: Muscle mitochondrial quantities
timeFrame: Changes from before to after the strength training intervention (week 19 to week 28)
measure: Muscle mitochondrial functions
timeFrame: Changes from before to after the strength training intervention (week 19 to week 28)
Other outcomes:
measure: Training diary
timeFrame: Measured over the course of the strength training familiarization period and the strength training intervention (week 15 to week 28)
measure: Dietary registration
timeFrame: Registred at one time point during the strength training intervention (~week 23, registred over four days)
measure: Self-reported information on lifestyle-related aspects
timeFrame: Measured over the course of the intervention (week 0 to week 28)
Locations:
city: Lillehammer
country: Norway
facility: Inland Norway University of Applied Sciences
Study officials:
affiliation: Inland Norway University of Applied Sciences
name: Knut Sindre Mølmen, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Molmen KS, Hammarstrom D, Falch GS, Grundtvig M, Koll L, Hanestadhaugen M, Khan Y, Ahmad R, Malerbakken B, Rodolen TJ, Lien R, Ronnestad BR, Raastad T, Ellefsen S. Chronic obstructive pulmonary disease does not impair responses to resistance training. J Transl Med. 2021 Jul 6;19(1):292. doi: 10.1186/s12967-021-02969-1.