The Effect of Calcifediol (Hy.D 25 SD/S) and Vitamin D3 on Muscle Strength in a Frail Elderly Population

Study Overview
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Brief Summary
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In an ageing population, the need for interventions to help older people remain healthy, active and independent for as long as possible, increases. Although several studies suggest a beneficial effect of vitamin D3 on maintaining or improving muscle strength and physical functioning, particularly in vulnerable populations, results are contradicting. Randomized, placebo-controlled trials are needed to further establish the effect of vitamin D on muscle strength in the frail elderly population.The primary aim of this study is to determine the effect of daily supplementation with two different forms of vitamin D on muscle strength in frail elderly people over a period of 24 weeks.

Official Title
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The Effect of Calcifediol (Hy.D 25 SD/S) and Vitamin D3 on Muscle Strength in a Frail Elderly Population: a Randomized, Double-blind, Placebo-controlled Trial.

Conditions
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Deficiency, Vitamin D, Elderly, Frail

Intervention / Treatment
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* Dietary Supplement: Calcifediol 10ug/day
* Dietary Supplement: Vitamin D3 20ug/day
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 25(OH)D levels 20-50 nmol/L. age 65 or older. physically frail (pre-frail or frail, based on the criteria designed by Fried et al.) (30). Frailty will be defined as a clinical syndrome in which one or more of the following criteria are present: unintentional weight loss (4.5 kg in past year), self-reported exhaustion (CES-D questionnaire), weakness (grip strength), slow walking speed and low physical activity (Minnesota questionnaire). More details on these criteria are described in chapter 6.3.2. body mass index between 18.5 and 35 kg/m2. willingness and ability to comply with the protocol, including performance of the knee extension strength test. Exclusion Criteria: Medical Illness: malabsorption syndrome: known intestinal malabsorption, celiac diseases, inflammatory bowel disease; diseases that may enhance serum calcium concentration: sarcoidosis, lymphoma, kidney stone in the last 10 years, primary hyperparathyroidism; abnormal indices of calcium metabolism, uncontrolled hypocalcaemia; diagnosed renal insufficiency; diagnosed cancer; currently diagnosed or undergoing treatment. Hypercalcemia: serum calcium adjusted for albumin of > 2.6 nmol/L. Medication: interfering with vitamin D metabolism and vitamin D supplementation (bisphosphonate, PTH treatment, tuberculostatica, anti-epileptica). Subject not able (when medically necessary/ advised) or not willing to stop the use of vitamin D containing supplements during the study. (Expected) increase in exposure to sunlight (e.g. travelling to a sunny resort) during intervention period. Patient heavily consumes alcohol containing products defined as greater than > 21 drinks of alcoholic beverages per week. Planned surgery which can affect study measures (taking into account duration of hospitalisation and recovery). Participation in another clinical trial.

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Calcifediol 10 ug/day<br>Capsule with 10 ug/day Calcifediol taken together with breakfast for a total period of 24 weeks. | Dietary Supplement: Calcifediol 10ug/day<br> <br> * Other names: Hy.D;|
| Experimental: Vitamin D3 20 ug/day<br>Capsule with 20 ug/day Vitamin D3 taken together with breakfast for a total period of 24 weeks. | Dietary Supplement: Vitamin D3 20ug/day<br> <br> * Other names: Cholecalciferol;|
| Placebo Comparator: Placebo<br>Capsule without active ingredients, taken together with breakfast for a total period of 24 weeks. | Dietary Supplement: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in muscle strength, knee extension strength (measured by Biodex System) | measured by Biodex System | baseline, week 12, end of study (after 24 weeks supplementation) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in knee flexion strength (measured by Biodex System) | measured by Biodex System | baseline, week 12, end of study (after 24 weeks supplementation) | 
| Change in handgrip strength |  | baseline, week 12, end of study (after 24 weeks supplementation) | 
| Change in SPPB |  | baseline, week 12, end of study (after 24 weeks supplementation) | 
| Change in Timed Up and Go test |  | baseline, week 12, end of study (after 24 weeks supplementation) | 
| Change in Postural Body Sway |  | baseline, week 12, end of study (after 24 weeks supplementation) | 
| Change in serum Vitamin D3 |  | baseline, week 12, end of study (after 24 weeks supplementation) | 
| Change in serum 25(OH)D |  | baseline, week 12, end of study (after 24 weeks supplementation) | 
| Change in serum 1,25(OH)2D3 |  | baseline, week 12, end of study (after 24 weeks supplementation) | 
| Change in serum 24,25(OH)2D |  | baseline, week 12, end of study (after 24 weeks supplementation) | 
| Frequency of falling |  | baseline, week 12, end of study (after 24 weeks supplementation) | 
| Change in muscle fibre type and size (Biopsy) | Biopsy | baseline, end of study (after 24 weeks supplementation) | 
| Change in body composition (DEXA-scan) | DEXA-scan | baseline, end of study (after 24 weeks supplementation) | 
| Change in cognitive functioning (Trail making, Stroop-test, Letter fluency) | Trail making, Stroop-test, Letter fluency | baseline, end of study (after 24 weeks supplementation) | 
| Change in vital Signs (blood pressure and heart rate) | blood pressure and heart rate | baseline, week 12, end of study (after 24 weeks supplementation) | 
| Change in neuromuscular measurements (MUNIX, MUSIX by EMG) | MUNIX, MUSIX by EMG | baseline, end of study (after 24 weeks supplementation) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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muscle strength, physical performance, vitamin D3, Cholecalciferol, Calcifediol