Prevention of Falls and Fractures in Old People by Administration of Calcium and Vitamin D. Randomized Clinical Trial

Study Overview
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Brief Summary
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The first objective is to determine the efficacy of calcium and vitamin D supplementation at doses of 1200 mg and 800 IU, respectively, to reduce the incidence of falls and fractures in non-institutionalized elderly people. The second objective is to measure and compare treatment groups (calcium and vitamin D vs placebo) as regards muscle strength and musculoskeletal function, bone mineral density, calcidiol level and treatment safety.

Detailed Description
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Background: There are many studies that associate vitamin D serum levels in older persons with muscle strength, physical performance and risk of fractures and falls. However, current evidence is insufficient to make a general recommendation for administrating calcium and vitamin D to older persons. The objective of this study is to determine the effectiveness of calcium and vitamin D supplementation in improving musculoskeletal function and decreasing the number of falls in person aged over 65 years. Design: Phase III, randomized, double blind, placebo-controlled trial to evaluate the efficacy of already marketed drugs in a new indication. It will be performed at Primary Care doctor visits at several Healthcare Centers in different Spanish Health Areas. A total of 704 non-institutionalized subjects aged 65 years or older will be studied (sample size calculated for a statistical power of 80%, alpha error 0.05, annual incidence of falls 30% and expected reduction of 30% to 20% and expected loss to follow up of 20%). The test drug containing 800 IU of vitamin D and 1000 mg of calcium will be administered daily. The control group will receive a placebo. The subjects will be followed up over two years. The primary variable will be the incidence of spontaneous falls. The secondary variables will include: consequences of the falls (fractures, need for hospitalization), change in calcidiol plasma levels and other analytical determinations (transaminases, PTH, calcium/phosphorous, albumin, creatinine, etc.), change in bone mass by densitometry, change in muscle strength in the dominant hand and change in musculoskeletal strength, risk factors for falls, treatment compliance, adverse effects and socio-demographic data.

Official Title
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Prevention of Falls and Fractures in Old People by Administration of Calcium and Vitamin D. Randomized Clinical Trial (ANVITAD)

Conditions
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Fall, Fractures

Intervention / Treatment
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* Drug: Vitamin D and calcium suplementation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged over 65 years with normal renal function Normal transaminase levels Normal calcium blood levels Not homebound (not immobilized) nor in socio-healthcare institutions. Exclusion Criteria: Need for medical treatment with calcium or vitamin D Hypersensitivity to or contraindication for calcium or vitamin D Medical treatment that includes calcium or vitamin D Physical disability that impedes their collaboration Taking thiazide diuretics Oral anticoagulants Hormone replacement therapy Digitalis drugs Anticonvulsants or barbiturates Having any of the following diseases: Lithiasis Renal impairment (serum creatinine >1.4 mg/dl) Hypo or hyperthyroidism Paget's disease Chronic liver disease Tumors Sarcoidosis Impaired intestinal absorption or chronic alcoholism (>40 g/day).

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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Calcium and vitamin D<br>The pharmacological intervention will be the daily administration of chewable tablets containing vitamin D and calcium. | Drug: Vitamin D and calcium suplementation<br>* The pharmacological intervention will be the daily administration of chewable tablets containing 800 IU of vitamin D and 1200 mg of calcium. They will be administered over 2 years during the months of November to April in order to avoid the influence of sunlight.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of spontaneous falls. | The primary variable will be the incidence of spontaneous falls according to the FICSIT (Frailty and Injury: Cooperative Study of Intervention Techniques) definition: Unintentionally coming to rest on the ground, floor, or other lower level. Coming to rest against furniture or a wall was not counted as a fall. | 24 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Consequence of falls. | Bone fractures at any location, need for healthcare, need for hospitalization, bed-ridden. | 24 months. | 
| Change in calcidiol [25(OH)D3] plasma levels | Determined by RIA (Vitamin D deficiency is defined as a calcidiol plasma level lower than 10ng/ml). | 18 months. | 
| Change in bone mass (bone density or mineral content). | By densitometry (risk of fracture). Osteoporosis will be diagnosed based on a densitometry T-score of less than 2.5 in the vertebral column, according to WHO criteria. | 24 months. | 
| Change in muscle strength in the dominant hand. | Determined by dyanometry (with a mean of 3 attempts to obtain a muscle strength measurement). | 24 months | 
| Changes in musculoskeletal function. | By the timed up and go test (the elderly person gets up from a chair with arms, walks three meters, turns round, walks back and sits down again). Taking more than 20 seconds indicates a high risk for falls. | 24 months | 
| Serious adverse events or any other adverse event. | An adverse event is considered as any untoward medical occurrence in any patient included in the study which does not necessarily have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product. | 24 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vitamin D, Calcium, Elderly