Vitamin D and Resistance Exercise Training; Effects on Musculoskeletal Health in Frail Older Men and Women

Study Overview
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Brief Summary
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This study aims to determine whether vitamin D3 supplementation is any more effective in improving musculoskeletal function when combined with exercise training compared with exercise training alone.

Detailed Description
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We are an ageing population with life expectancy currently increasing at 2 years per decade. Crucially, healthy life expectancy is not keeping pace and older adults are now spending longer in poor health. Sarcopenia represents a major, serious and increasing public health problem. While the causes of sarcopenia are still unclear, vitamin D deficiency, which is widespread among older adults (reaching 90% in residential care), is associated with an increased risk of falls and fractures as well as skeletal muscle weakness. While it is known that vitamin D is essential for bone health, relatively little is known about the direct effects of vitamin D3 supplementation on human muscle mass and function in humans. Physical activity (resistance exercise training (RET) in particular) is the most potent stimulus for skeletal muscle hypertrophy in both young and older adults. The researchers and others have shown that even in very old adults (>75 years) and frail patient groups, RET improves muscle strength and functional outcomes although the hypertrophic ability of older muscle is blunted compared with younger adults. Therefore in order to help older adults maintain good musculoskeletal health, interventions to optimise responsiveness to physical activity are likely to be most effective if they are multimodal, and include resistance exercise. One example of this is to combine resistance exercise training with vitamin D supplementation. The aim of the EXVITD study is to determine whether vitamin D3 supplementation is any more effective in improving musculoskeletal function when combined with exercise training compared with exercise training alone. The researchers aim to recruit 127 men and women aged 65 years or over who are ambulatory (with or without walking aids) and live in supported housing settings. Recruitment will be via local housing trusts/seniors groups. Participants will be randomised to RET (x3 per week) + 800 International Units (IU) vitamin D3 (daily) supplement or RET + placebo for six months. Participants will be stratified on the basis of vitamin D status, physical activity (measured directly pre-randomisation using accelerometry), and sex. Tests will include, but are not limited to, lower limb extensor power (LLEP) output, body composition, Short Physical Performance Battery (SPPB), Timed-up-and-go (TUG),power required to rise from a chair, physical activity, perception of musculoskeletal comfort/pain, falls as events, quality of life and venepuncture for biochemical markers.

Official Title
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Influence of Combined Vitamin D Supplementation and Resistance Exercise Training on Musculoskeletal Health in Frail Older Men and Women (EXVITD)

Conditions
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Sarcopenia, Muscle Atrophy, Osteoporosis

Intervention / Treatment
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* Other: RET
* Dietary Supplement: Placebo
* Dietary Supplement: Vitamin D3


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 65 years or over Ambulatory (with or without walking aids) Exclusion Criteria: History of myocardial infarction within previous 2 years Cardiac illness: moderate/ severe aortic stenosis, acute pericarditis, acute myocarditis, aneurysm, severe angina, clinically significant valvular disease, uncontrolled dysrhythmia, claudication within the previous 10 years; thrombophlebitis or pulmonary embolus within the previous 2 years History of cerebrovascular disease (CVA or TIA) within the previous 2 years Acute febrile illness within the previous 3 months Severe airflow obstruction; uncontrolled metabolic disease (e.g., thyroid disease or cancer) Significant emotional distress, psychotic illness or depression within the previous 2 years Lower limb fracture sustained within the previous 2 years/ upper limb fracture within the previous 6 months Non-arthroscopic lower limb joint surgery within the previous 2 years Any reason for loss of mobility for greater than 1 week in the previous 2 months or greater than 2 weeks in the previous 6 months Resting systolic pressure >200 millimeters of mercury (mmHg) or resting diastolic pressure >100 mmHg Poorly controlled atrial fibrillation; poor (chronic) pain control Moderate/severe cognitive impairment (mini mental state examination (MMSE) score <23) Vitamin D deficient (serum 25(OH)D3 <30nmol/l); current antiresorptive or anabolic treatment for osteoporosis Treatment with bisphosphonates for osteoporosis in the past two years Current supplement use of vitamin D (>400 IU/day) or calcium (>500 mg/day including use of over the counter preparations) Current use of glucocorticoids; known primary hyperparathyroidism; hypercalcaemia (albumin-adjusted serum calcium >2.60 mmol/l) Renal impairment (Stage 4 or 5)

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RET + vitamin D3<br>Resistance Exercise Training (RET) + vitamin D3 given orally as tablets at a dosage of 800 International Units (IU)/day for 6 months. | Other: RET<br>* RET: A supervised group exercise programme with a maximum of n=10-12 participants per group to be attended 3 times per week for 6 months. The RET programme includes elements of current established programmes for falls prevention/ core stability (i.e., OTAGO, PEPPI) and will tailored to a range of abilities within the target group. Vitamin D3 supplementation: vitamin D3 given orally as tablets at a dosage of 800 IU/day for 6 months.<br>Dietary Supplement: Vitamin D3<br>* Placebo given orally as tablets; 800 IU as 1 tablet per day for 6 months.<br>|
| Placebo Comparator: RET + placebo<br>Resistance Exercise Training (RET) + placebo given orally as tablets; 1 tablet per day for 6 months. | Dietary Supplement: Placebo<br>* Placebo given orally as tablets; 1 tablet per day for 6 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lower limb extensor power (LLEP) | Nottingham Leg Extensor Power Rig | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body composition and bone mineral density (BMD) | Body composition, hip and spine BMD measured using dual-energy X-ray absorptiometry (DXA) | 6 months | 
| Short Physical Performance Battery (SPPB) | Gait speed, chair stand, balance tests | 6 months | 
| Timed-up-and-go (TUG) | To assess mobility | 6 months | 
| Physical activity | Directly monitored physical activity using accelerometry (ActivPAL) | 6 months | 
| Falls as events | Incidence of falls | 6 months | 
| Quality of life (QoL) | QoL assessed via questionnaire | 6 months | 
| Serum blood monitoring | Venepuncture for markers of inflammation plus monitoring of serum vitamin D3 and calcium status at baseline, 1, 3 and 6 months. | 6 months | 
| Muscle power | Chair rise test using Leonardo Mechanograph Ground Reaction Force Plate | 6 months | 
| 3-day Dietary analysis | 3-day food diary record | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sarcopenia, Older adult, Vitamin D, Physical activity, Muscle atrophy, Muscle strength, Physical function, Frailty, Osteoporosis