The Effect of Cholecalciferol in Pre-frail Elderly

Study Overview
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Brief Summary
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Vitamin D plays important role in musculoskeletal health and has been known to influence immune system. Inflammaging is one of risk factors that may contribute to development of frailty in elderly. The purpose of this study is to determine the effects of cholecalciferol in pre-frail elderly receiving calcium supplementation on handgrip strength, gait speed, vitamin D receptor, IGF-1 and IL-6. Fall incidence and improvement of frailty status will also be assessed.

Detailed Description
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This is a randomized double-blind placebo-controlled study in pre-frail elderly. Measurement of frailty status based on Fried frailty phenotype criteria (weight loss, weakness, exhaustion, slowness, low physical activity level) . Subjects who fulfill eligibility criteria will be randomized into 2 groups, one group will received cholecalciferol 4000 IU once daily and the other group will received placebo once daily. Each subjects in both groups will received calcium lactate 500 mg once daily. Intervention will be held for 12 weeks. Handgrip strength and gait speed will be assessed at baseline, every 4 weeks, and at week 12. Other outcome measures will be assessed at baseline and at week 12.

Official Title
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The Effect of Cholecalciferol on Frailty Syndrome in Pre-frail Elderly Receiving Calcium Supplementation : A Study on Handgrip Strength, Gait Speed, Vitamin D Receptor, Insulin Growth Factor-1 and Interleukin-6

Conditions
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Pre-frail Elderly

Intervention / Treatment
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* Drug: Cholecalciferol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pre-frail elderly Capable to understand and carry-out the instruction Exclusion Criteria: Allergic to cholecalciferol, calcium, or its components Hypercalcemia (total serum calcium > 10,5 mg/dL) Unwilling to stop using drug contain vitamin D or vitamin D analog or calcium Using steroid or NSAID routinely Acute illness during inclusion period, eg. pneumonia, stroke attack, acute exacerbation of chronic obstructive pulmonary disease, asthma attack, hypertensive urgency/emergency, acute decompensated heart failure Having condition that can affect measurement of handgrip strength and gait speed, eg. hemiparesis, severe pain in extremities Hepatic cirrhosis, malignancy, autoimmune disease, nephrolithiasis, malabsorption syndrome (eg. chronic diarrhea) , diabetes mellitus with HbA1c > = 8% in the last 3 months, diabetes mellitus with obvious sign and symptoms of catabolic decompensation (polyphagia, polydipsia, polyuria), chronic kidney disease stage IV-V or decreased renal function with estimated glomerular filtration rate < 30 ml/minute/1,73 m2 Using drug that can affect vitamin D absorption, eg. bile acid sequestrants Cognitive impairment (Abbreviated Mental Test score < 8) Depression (Geriatric Depression Scale score > = 10) Unwilling to join the study

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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: Interventional group<br>Oral capsule Cholecalciferol 4000 IU once daily and Calcium Lactate 500 mg once daily for 12 weeks. | Drug: Cholecalciferol<br>* Oral capsule Cholecalciferol 4000 IU once daily and Calcium Lactate 500 mg once daily for 12 weeks<br>* Other names: Prove D3;|
| Placebo Comparator: Control Group<br>Oral capsule Placebo once daily and Calcium Lactate 500 mg once daily for 12 weeks. | Drug: Placebo<br>* Oral capsule Placebo containing white rice flour in the same identical looking with active drug once daily and Calcium Lactate 500 mg once daily for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Handgrip strength | Change from baseline in handgrip strength. Measurement: handgrip dynamometer (Jamar Hydraulic Hand Dynamometer ) | 12 weeks (evaluation every 4 weeks) | 
| Gait speed | Change from baseline in gait speed. Measurement: 15-feet walking test | 12 weeks (evaluation every 4 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vitamin D receptor (VDR) monocyte level | Change from baseline in VDR monocyte level. Measurement : flowcytometry | 12 weeks | 
| Interleukine 6 (IL-6) monocyte level | Change from baseline in IL-6 monocyte level. Measurement : flowcytometry | 12 weeks | 
| Insulin Growth Factor-1 (IGF-1) monocyte level | Change from baseline in IGF-1 monocyte level. Measurement : flowcytometry | 12 weeks | 
| serum VDR level | change from baseline in serum VDR level. Measurement : ELISA | 12 weeks | 
| Serum IGF-1 level | change from baseline in serum IGF-1 level. Measurement : ELISA | 12 weeks | 
| serum IL-6 level | change from baseline in serum IL-6 level. Measurement : ELISA | 12 weeks | 
| Fall incidence | number of fall | 12 weeks | 
| Frailty status | improvement in frailty status | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Frailty, Pre-frail, Elderly, Cholecalciferol, Handgrip strength, Gait speed, Vitamin D receptor, Insulin Growth Factor-1, Interleukin-6