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

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

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.

Study Overview

• Status: Completed
• Conditions: Sarcopenia; Osteoporosis; Muscle Atrophy
• Intervention / Treatment: Other: RET; Dietary supplement: Vitamin D3; Dietary supplement: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Birmingham, United Kingdom, B15 2TT
    • University of Birmingham

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RET + vitamin D3; Resistance Exercise Training (RET) + vitamin D3 given orally as tablets at a dosage of 800 International Units (IU)/day for 6 months.	Other: RET; 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.; Dietary supplement: Vitamin D3; Placebo given orally as tablets; 800 IU as 1 tablet per day for 6 months.
Placebo Comparator: RET + placebo; Resistance Exercise Training (RET) + placebo given orally as tablets; 1 tablet per day for 6 months.	Dietary supplement: Placebo; Placebo given orally as tablets; 1 tablet per day for 6 months.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Birmingham
• Collaborators: University of Surrey; University Hospital Birmingham
• Investigators: Principal Investigator: Carolyn Greig, PhD, University of Birmingham

Publications and helpful links

General Publications

• Welford AE, Lanham-New S, Lord J, Doyle A, Robinson J, Nightingale P, Gittoes N, Greig CA. Influence of combined vitamin D3 supplementation and resistance exercise training on musculoskeletal health in older men and women (EXVITD): protocol for a randomised controlled trial. BMJ Open. 2020 Mar 18;10(3):e033824. doi: 10.1136/bmjopen-2019-033824.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Actual): October 31, 2019
• Study Completion (Actual): December 16, 2019

Study Registration Dates

• First Submitted: May 11, 2015
• First Submitted That Met QC Criteria: June 8, 2015
• First Posted (Estimate): June 9, 2015

Study Record Updates

• Last Update Posted (Actual): February 10, 2022
• Last Update Submitted That Met QC Criteria: February 7, 2022
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Vitamin D; Physical activity; Sarcopenia; Osteoporosis; Muscle strength; Frailty; Physical function; Muscle atrophy; Older adult
• Additional Relevant MeSH Terms: Metabolic Diseases; Nervous System Diseases; Neurologic Manifestations; Musculoskeletal Diseases; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Bone Diseases; Bone Diseases, Metabolic; Sarcopenia; Muscular Atrophy; Osteoporosis; Atrophy; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: RG_14-185