Study To Understand Fall Reduction and Vitamin D in You

Study Overview
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Brief Summary
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Vitamin D supplements might substantially reduce the risk of falls, potentially by more than 25%. The proposed study is a clinical trial that will determine the effects of 4 doses of vitamin D (200 International Units [IU]/day, 1000 IU/day, 2000 IU/d and 4000 IU/d) as a means to prevent falls in high-risk adults, ages 70 and older. Results of this trial will be directly relevant to public health and clinical guidelines, and will immediately influence policy.

Detailed Description
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The public health burden of falls in older persons is substantial. Several lines of evidence suggest that vitamin D supplements might reduce the risk of falls, potentially by 25% or more in persons with low serum 25-hydroxyvitamin D [25(OH)D] levels. However, existing evidence is inconsistent and insufficient to guide policy. The trial is a seamless two-stage, Bayesian response-adaptive, randomized dose-finding trial designed to select the best dose of vitamin D supplementation and to potentially confirm the efficacy of that dose for fall prevention and other related outcomes. Participants will be community-dwelling adults, aged 70+ (goal of  40% black,  60% women), with a baseline serum 25(OH)D level of 10-29 ng/ml, who are at high risk for falling. In Stage 1 of the adaptive design, participants will be randomly assigned to one of four vitamin D3 (cholecalciferol) doses: 200 IU/d (control), 1000 IU/d, 2000 IU/d, or 4000 IU/d, with assignment probabilities that will vary as falls are reported. Participants will take their assigned pills for two years, or until the study ends, whichever comes first. This stage of the design will select the best non control dose of vitamin D for prevention of falls, or confirm the futility of distinguishing any differences among the non control doses for fall prevention. If a best dose is selected, subsequent participants will be randomized in Stage 2 of the trial into the comparison (200 IU/d) or best dose group, and all participants (Stage 1 and Stage 2) will continue to be followed to potentially confirm efficacy. The investigators anticipate enrolling approximately 1,200 participants over the entire length of the project. The primary outcome is time to first fall (or death) over two years of therapy. Next in importance is the outcome of gait speed. Other outcomes include fall rates, types of falls, balance, muscle strength, frailty, Short Physical Performance Battery (SPPB) score, 6-minute walk time, and physical activity assessed by accelerometry. Falls will be ascertained from fall calendars completed daily by participants and from self-report by phone. In-person follow-up visits will occur at 3, 12, and 24 months, with telephone visits occurring at 1, 6, 9, 15, 18, and 21 months after randomization. Subgroups with potential for greater benefit from vitamin D supplementation are blacks, those with baseline 25(OH)D of 10-19 ng/ml, and those with objective evidence of low physical function.

Official Title
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Vitamin D Supplements to Prevent Falls in Older Adults: A Dose-Response Trial

Conditions
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Vitamin D Deficiency, Falls

Intervention / Treatment
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* Dietary Supplement: 200 IU/d cholecalciferol
* Dietary Supplement: 1000 IU/d cholecalciferol
* Dietary Supplement: 2000 IU/d cholecalciferol
* Dietary Supplement: 4000 IU/d cholecalciferol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 70 and older Non-institutionalized High risk for falling, defined by a 'yes' response to at least one of the following: 1. Have you fallen and hurt yourself in the past year? 2. Have you fallen 2 or more times in the past year? 3. Are you afraid that you might fall because of balance or walking problems? 4. Do you have difficulty maintaining your balance when bathing, dressing, or getting in and out of a chair? 5. Do you use a cane, walker, or other device when walking inside or outside your home? Serum vitamin D [25(OH)D] level of 10-29 ng/ml Able to provide informed consent Willing to accept randomization to each vitamin D dose One of the following: 1. No vitamin D supplementation at baseline 2. Average daily vitamin D supplementation judged by study staff as being consistent with the goal of 1000 IU/day or less at screening and willing to continue the dose unchanged throughout the trial One of the following: 1. No calcium supplementation at baseline 2. Average daily calcium supplementation judged by study staff as being consistent with the goal of 1200 mg/day or less at screening and willing to continue the dose unchanged throughout the trial Exclusion Criteria: Cognitive impairment, defined by Mini-Mental State Exam (MMSE) score <24 Hypercalcemia, serum Ca++ 11.0 mg/dl or higher or >10.5 mg/dl (confirmed) Hypocalcemia, serum Ca++ <8.5 mg/dl Kidney, ureteral, or bladder stones made of calcium compounds (2 or more in lifetime, or 1 in the last 2 years); in the absence of information on the type of stone, stones will be assumed to be made of calcium compounds Planning to move out of area within 2 years, where plans would prevent compliance with the study protocol Disease or condition expected to cause death or to prevent compliance with the study protocol in the next 2 years Participation in another trial of vitamin D or falls, or any trial that might affect the risk of falls Lactose allergy (lactose intolerance is okay) Use of any form of oral or injected calcitriol (brand names: Rocaltrol (R), Calcijex (R), and Zemplar (R); generic names: calcitriol, paricalcitol, doxycalcitriol, 22-oxacalcitriol)

Ages Eligible for Study
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Minimum Age: 70 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 200 IU/d<br>200 IU/d cholecalciferol (vitamin D3) tablets that can be swallowed or consumed sublingually | Dietary Supplement: 200 IU/d cholecalciferol<br> <br> * Other names: vitamin D3;|
| Active Comparator: 1000 IU/d<br>1000 IU/d cholecalciferol (vitamin D3) tablets that can be swallowed or consumed sublingually | Dietary Supplement: 1000 IU/d cholecalciferol<br> <br> * Other names: vitamin D3;|
| Active Comparator: 2000 IU/d<br>2000 IU/d cholecalciferol (vitamin D3) tablets that can be swallowed or consumed sublingually | Dietary Supplement: 2000 IU/d cholecalciferol<br> <br> * Other names: vitamin D3;|
| Active Comparator: 4000 IU/d<br>4000 IU/d cholecalciferol (vitamin D3) tablets that can be swallowed or consumed sublingually | Dietary Supplement: 4000 IU/d cholecalciferol<br> <br> * Other names: vitamin D3;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of First Fall or Death (Whichever Comes First) | Falls were ascertained by a monthly fall calendar completed by each participant, scheduled interviews at 1 month and 3 months after randomization and every 3 months thereafter up to 24 months or trial end. Death was ascertained primarily by reports from family or friends. | Randomization to 24 months or end of trial, whichever came first | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Gait Speed | Gait speed in meters per second (m/s) was obtained from the timed 4-meter, usual-paced walk component of the Short Physical Performance Battery. The change in gait speed was obtained as follow-up measure minus baseline measure. | Baseline, 3 months, 12 months and 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vitamin D, falls, high risk of falling, insufficient or deficient serum vitamin D levels, 10-29 ng/ml