Zurich Disability Prevention Trial

Study Overview
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Brief Summary
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This project was designed to optimizing vitamin D status in prefrail seniors age 70+ living at home and prevent their functional decline. We test 3 arms of monthly vitamin D supplementation. Intermittent dosing will improve adherence and simplify vitamin D supplementation.

Detailed Description
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We propose a double-blind, randomized controlled trial to test the effectiveness of a Active I (n=70): monthly high-dose vitamin D3 supplement dose (60'000 IU/month, equivalent to 2000 IU daily), Active II (n=70): or a monthly standard vitamin D3 supplement dose combined with 25(OH)D (24'000 IU/month, equivalent to 800 IU daily PLUS 300 mcg 25(OH)D, equivalent to 10 mcg per day) Control (n=70): compared to a standard vitamin D3 supplement dose (24'000 IU/month, equivalent to 800 IU daily) All individuals will be advised to consume calcium from natural food sources in a daily dose of 600-800 mgs a day, including milk products. Maximal intake of supplemental calcium is restricted to 250 mg per day.

Official Title
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Monthly Vitamin D to Improve Vitamin D Status and Maintain Function in Pre-frail Older Individuals Living at Home

Conditions
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Community-dwelling Seniors, History of a Fall in the Previous 12 Months

Intervention / Treatment
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* Drug: Hidroferol® (ES)
* Dietary Supplement: ViDe3 (CH)
* Dietary Supplement: ViDe3 (CH)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Age 70+ Fall in the last 12 months before screening (with or without a fracture) Living at home (community-dwelling) Men or women Mobile with or without walking aid - have to be able to use public transportation to attend the clinical visits at the trial centre Score of at least 27 at the screening Folstein Mini Mental test + normal clock test Patient understands the study procedures, alternative treatments available and risks involved with the study, and voluntarily agrees to participate by giving a written informed consents. Patient meets the entry minimal requirements based on routine clinical laboratory safety screening tests and the Folstein mini mental status (score 27+ required) performed at the Screening Visit. Patient is willing to perform all study tests, attend all required office visits, and provide blood and urine samples. Exclusion criteria: Serum calcium adjusted for albumin of > 2.6 nmol/l Pathologic fracture in the last year (except for fractures due to osteoporosis) Chemo therapy / Radiation due to cancer in the last year Treatment which has an effect on bone metabolism (e.g. bisphosphonate, PTH, calcitonin, chronic cortisone intake > XYmg/day for more than XY month/years (except for inhalation and sporadic infiltration)) Oral vitamin D intake of more than 800 IU per day Unwilling to stop calcium supplementation and vitamin D supplementation during the trial (maximal calcium supplement intake 250mg/d; no additional vitamin D supplementation) Severe visual or hearing impairment Unwilling or unable to take study medication Diseases with a risk of recurrent falling (e.g. Parkinson's disease/syndrome, Hemiplegia after stroke, symptomatic stenosis of the spinal canal, polyneuropathy, epilepsy, recurring vertigo, recurring syncope) BMI >= 40 Estimated creatinine clearance < 15 ml/min (estimated Creatinine Clearance Cockcroft and Gault) Malabsorption syndrome (celiac diseases, inflammatory bowl disease) Diseases that may enhance serum calcium: sarcoidosis, lymphoma, primary hyperparathyroidism kidney stone in the last 10 years Abnormal indices of calcium metabolism, uncontrolled hypocalcemia. Patient heavily consumes alcohol containing products defined as greater than (>) 3 drinks (beer, wine, or distilled spirits) of alcoholic beverages per day. Patient is unlikely to adhere to the study procedures, to keep appointments, or is planning to relocate during the study. Patients who are planning a stay in a sunny location (e.g. winter sun resort) for more than two months per year Medication which has an effect on 25-hydroxyvitamin D level (e.g. certain anticonvulsants (e.g. Phenobarbital, Carbamazepin, Phenytoin)) M. Paget (Ostitis deformans) inflammatory arthritis (e.g. rheumatoid arthritis, reiter syndrome, psoriasis arthritis)

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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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: High-dose vitamin D3<br>monthly high-dose vitamin D3 supplement dose (60'000 IU/month, equivalent to 2000 IU daily) | Dietary Supplement: ViDe3 (CH)<br>* 60000 vitamin D3 orally and once per month<br>|
| Experimental: standard vitamin D + 25(OH)D<br>standard vitamin D3 supplement dose combined with 25(OH)D (24'000 IU/month, equivalent to 800 IU daily PLUS 300 mcg 25(OH)D, equivalent to 10 mcg per day) | Drug: Hidroferol® (ES)<br>* 24000 IU vitamin D3 orally and once per month plus 300 mcg 25(OH)D orally and once per month<br>|
| Active Comparator: standard vitamin D<br>standard vitamin D3 supplement dose (24'000 IU/month, equivalent to 800 IU daily) | Dietary Supplement: ViDe3 (CH)<br>* 24000 Vitamin D3 orally and once per month<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| functional decline (proportion of individuals with functional decline based on binary repeated measure assessment across 4 lower extremity tests) |  | 6 and 12 months | 
| Improving 25-hydroxyvitamin D levels in late winter and late summer - Percent of individuals reaching desirable 25-hydroxyvitamin D levels of at least 75 nmol/l in late winter and in late summer |  | 6 and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety at baseline, 2 weeks, 6 months, 12 months • Serum calcium adjusted for albumin • Serum creatinine • Urinary calcium/creatinine ratio |  | 2 weeks, 6 months, 12 months | 
| Balance/Gait while walking combined with a cognitive task |  | 12 months | 
| Short Physical Performance Test Battery |  | 6 months, 12 months | 
| Timed 4 m walk |  | 6 months, 12 months | 
| Musculoskeletal pain assessed with the McGill pain map |  | 6 months and 12 months | 
| systolic and diastolic blood pressure, heart rate |  | 6 month and 12 months | 
| Rate of falls, all, injurious falls (diary, monthly phone calls, and hotline) |  | 12 months | 
| grip strength |  | 6 months and 12 months | 
| Bone density at the spine and hip, whole body |  | 6 months and 12 months | 
| incident vertebral fractures (iDXA morphometry) |  | 12 months | 
| muscle mass, incident sarcopenia |  | 6 and 12 months | 
| Health care utilization: in collaboration with insurance companies for outpatient and inpatient health care costs. |  | 12 months | 
| Quality of life (SF 12 / EuroQuol) |  | 6 months and 12 months | 
| Rate of hospital admission (fall-related injury, infections, other) |  | 12 months | 
| Serum N-telopeptides and other markers of bone remodeling |  | 6 months and 12 months | 
| Upper and lower respiratory tract infections, any infections, infections that lead to inpatient care |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vitamin D, function, falls, 25-hydroxyvitamin D, disability