The Granheim COPD Study - Vitamin D and Strength Training

Chronic Obstructive Pulmonary Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02598830
• Other study ID #: Trainsome 2014#004
• Status: Completed
• Phase: N/A
• Start date: November 2015
• Est. completion date: June 2018

Study information

• Verified date: December 2018
• Source: Inland Norway University of Applied Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 97
• Est. completion date: June 2018
• Est. primary completion date: June 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 45 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Dietary Supplement:
• Vitamin D3
Vitamin D3 dissolved in olive oil, encapsuled
• Placebo
Olive oil, encapsuled

Locations

Country	Name	City	State
Norway	Inland Norway University of Applied Sciences	Lillehammer

Sponsors (6)

Lead Sponsor	Collaborator
Inland Norway University of Applied Sciences	Lillehammer Hospital for Rheumatic Diseases, Norwegian School of Sport Sciences, Sykehuset Innlandet HF, University of Bergen, University of Copenhagen

Country where clinical trial is conducted

Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Training diary	Training diary containing information about type of training, duration of training and training intensity	Measured over the course of the strength training familiarization period and the strength training intervention (week 15 to week 28)
Other	Dietary registration	Detailed registration of food intake	Registred at one time point during the strength training intervention (~week 23, registred over four days)
Other	Self-reported information on lifestyle-related aspects	Disease, symptoms, injury, vitamin D-intake, time spent outdoors, solarium, training background, smoking, etc	Measured over the course of the intervention (week 0 to week 28)
Primary	Muscle size	Muscle cell cross-sectional area measured in biopsies from m. vastus lateralis using immunohistochemistry	Changes from before to after the strength training intervention (week 19 to week 28)
Primary	Muscle phenotype	Muscle fiber type composition measured in biopsies from m. vastus lateralis using immunohistochemistry	Changes from before to after the strength training intervention (week 19 to week 28)
Secondary	Lung function	Lung function measured using spirometry	Changes from before to after the strength training intervention (week 19 to week 28)
Secondary	One-legged cycling	Performance indicies measured during an incremental one-legged cycling test	Changes from before to after the strength training intervention (week 19 to week 28)
Secondary	Hormones in blood	Levels of hormones in blood	Changes over the course of the intervention (week 0 to 28)
Secondary	Cytokines in blood	Levels of cytokines in blood	Changes over the course of the intervention (week 0 to 28)
Secondary	Steroids in skeletal muscle	Levels of steroids in m. vastus lateralis	Changes over the course of the intervention (week 0 to 28)
Secondary	Androgen-converting enzymes in skeletal muscle	Levels of androgen-converting enzymes in m. vastus lateralis	Changes from before to after the strength training intervention (week 19 to week 28)
Secondary	Gene expression in skeletal muscle	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	Changes from before to after the strength training intervention (week 19 to week 28)
Secondary	Gene expression in skeletal muscle	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	Changes from before to after familiarization to strength training (week 15 to week 17)
Secondary	Protein abundances in skeletal muscle	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	Changes from before to after the strength training intervention (week 19 to week 28)
Secondary	Protein abundances in skeletal muscle	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	Changes from before to after familiarization to strength training (week 15 to week 17)
Secondary	Vitamin D in blood	Levels of vitamin D in blood	Changes over the course of the intervention (week 0 to 28)
Secondary	Step test	Performance and performance indicies measured during a 6 minutes step test	Changes from before to after the strength training intervention (week 19 to week 28)
Secondary	Pasient-reported outcome measures, generic	Pasient-related outcome measures assessed using the generic survey SF-36	Changes from before to after the strength training intervention (week 19 to week 28)
Secondary	Pasient-reported outcome measures, COPD-specific	COPD-specific pasient-reported outcome assessed using COPD assessment test	Changes from before to after the strength training intervention (week 19 to week 28)
Secondary	Body mass composition	Body mass composition measured using Dual-energy X-ray absorptiometry (DXA)	Changes from before to after the strength training intervention (week 19 to week 28)
Secondary	Bilateral upper body maximal strength	The ability of muscles of the upper body to exert maximal force during dynamic movements	Changes from before to after the strength training intervention (week 19 to week 28)
Secondary	Grip strength	Isometric hand grip strength	Changes from before to after the strength training intervention (week 19 to week 28)
Secondary	Sit-to-stand test	Performance and performance indicies measured during a sit-to-stand test	Changes from before to after the strength training intervention (week 19 to week 28)
Secondary	Unilateral lower body maximal muscle strength	The ability of muscles of the lower body to exert maximal force during dynamic movements	Changes from before to after the strength training intervention (week 19 to week 28)
Secondary	Unilateral lower body muscle endurance	The ability of muscles of the lower body to perform repeated dynamic contractions at a specified submaximal load to exhaustion	Changes from before to after the strength training intervention (week 19 to week 28)
Secondary	Bilateral upper body muscle endurance	The ability of muscles of the upper body to perform repeated dynamic contractions at a specified submaximal load to exhaustion	Changes from before to after the strength training intervention (week 19 to week 28)
Secondary	Unilateral lower body isokinetic muscle strength	The ability of muscles of the lower body to exert maximal force during isokinetic movements	Changes from before to after the strength training intervention (week 19 to week 28)
Secondary	Daily life activity level	Daily life activity level measured using accelerometer	Changes from before to after the intervention (week 0 to week 28)
Secondary	Muscle cell biological traits	Muscle cell biological traits, including numbers of myonuclei, satelitte cells and capillaries, measured in biopsies from m. vastus lateralis using immunohistochemistry	Changes from before to after the strength training intervention (week 19 to week 28)
Secondary	Muscle mitochondrial quantities	Mitochondrial quantities measured in biopsies from m. vastus lateralis	Changes from before to after the strength training intervention (week 19 to week 28)
Secondary	Muscle mitochondrial functions	Mitochondrial functions measured in biopsies from m. vastus lateralis	Changes from before to after the strength training intervention (week 19 to week 28)