Zurich Multiple Endpoint Vitamin D Trial in Knee OA Patients

Study Overview
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Brief Summary
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This is a 2-year double-blind randomized controlled trial in 287 community-dwelling individuals age 60 years or older undergoing uni-lateral total knee replacement due to severe OA of the knee.We compare an oral dose of 2000 IU vitamin D3 per day to 800 IU. The primary endpoints are pain and disability related to rehabilitation of the operated knee,and related to the expected high prevalence of OA in the contra-lateral knee. Secondary endpoints are change in 25(OH)D levels, muscle strength, balance, lower extremity function, the rate of falls, bone density and bone quality, bone metabolism, general pain, fall-related fractures, body composition, blood-pressure, major cardiovascular events, blood glucose-insulin levels, executive cognitive function, rate of upper respiratory tract infections / all infections, tooth loss, dental health, health care utilization, number and size of facial skin keratosis, and radiographic progression of the non-operated knee. Pain and disability will be assessed by the pain and function subscales of the Western Ontario- McMaster Universities Osteoarthritis Index (WOMAC). Randomization will be stratified by WOMAC function prior to surgery, radiological evidence for OA in the contra-lateral knee, and hospital. Clinical visits will take place at baseline (6-8 weeks after TKR), at 6, 12, 18 and 24 months of treatment. In addition, all individuals will receive a phone call every 2 month to assess adverse outcomes and compliance to treatment, supported by a hotline for immediate report of adverse events. Statistical power: We expect more than 80% power with 200 participants completing their 24 month follow-up, and 260 participants completing their 12 month follow-up. This is a trial with medicinal product.

Official Title
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Role of Vitamin D in Secondary Prevention of Knee Osteoarthritis: A Double-blind Randomized Controlled Trial

Conditions
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Knee Osteoarthritis

Intervention / Treatment
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* Dietary Supplement: Vitamin D3 (cholecalciferol)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Unilateral knee replacement due to knee osteoarthritis Age 60+ years German language skills community dwelling Exclusion Criteria: Bi-lateral knee replacement or hip replacement planned in the trial period, or in the previous 6 months Chronic steroid intake Serum calcium corrected for serum albumin > 2.6 mmol/l GFR < 30 ml/min Severe visual or hearing impairment Inflammatory arthritis Malabsorption High alcohol intake Sarcoidosis, primary hyperparathyroidism History of kidney stones, lymphoma Chemotherapy for cancer in the previous 12 months Hemiplegia Morbus Parkinson Unable to walk 3 meters prior to surgery Bisphosphonate, parathyroid hormone , fluoride or calcitonine therapy in the last 6 months Zolendronate in the last year M. Paget (Ostitis deformans) Vitamin D3 intake more than 800IU/d over more than 1 month stay on a sunny location for more than 6 weeks per year heart failure

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 |
| --- | --- |
| Active Comparator: 1: 2000 IU D3/day<br>2000 IU vitamin D3 taken orally each day for 2 years | Dietary Supplement: Vitamin D3 (cholecalciferol)<br>* the intervention is a dietary supplement comparing the current standard (800 IU) to the current safe upper limit (2000 IU)<br>|
| Active Comparator: 2: 800 IU D3 / day<br>800 IU vitamin D3 taken orally each day for 2 years | Dietary Supplement: Vitamin D3 (cholecalciferol)<br>* the intervention is a dietary supplement comparing the current standard (800 IU) to the current safe upper limit (2000 IU)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pain and function of the operated and non-operated knee |  | 0, 6,12,18, 24 months | 
| rate of falls |  | 0, 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| strength, balance, function, physical activity |  | 0,6,12,18,24 months | 
| bone density, bone quality |  | 0, 24 months | 
| body composition |  | 0, 24 months | 
| blood pressure |  | 0,12,24 months | 
| number of teeth |  | 0, 24 months | 
| cost, health care utilization |  | 0,6,12,18,24 months | 
| facial skin keratosis (number and size) |  | 0, 24 months | 
| cognitive function |  | 0, 24 months | 
| depression, mental health |  | 0,12,24 months | 
| fasting blood glucose - insulin levels |  | 0,12,24 | 
| Number of upper respiratory infections and number of any infections |  | 0, 6,12,28,24 | 
| bone metabolism |  | 0,6,12,18,24 | 
| radiographic progression of the non-operated knee |  | 0, 24 months | 
| general pain |  | 0,6,12,18,24 months | 
| Quality of life |  | 0,6,12,18,24 |