Clinical trial NCT00599807: Zurich Multiple Endpoint Vitamin D Trial in Knee OA Patients
Official title: Role of Vitamin D in Secondary Prevention of Knee Osteoarthritis: A Double-blind Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Knee Osteoarthritis
Lead sponsor: University of Zurich
Sponsor class: OTHER
Collaborators: name: Harvard School of Public Health (HSPH)
name: Tufts University
name: Boston University
First posted: 2008-01-24
Enrollment: 273
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: pain and function of the operated and non-operated knee
timeFrame: 0, 6,12,18, 24 months
measure: rate of falls
timeFrame: 0, 24 months
Secondary outcomes:
measure: strength, balance, function, physical activity
timeFrame: 0,6,12,18,24 months
measure: bone density, bone quality
timeFrame: 0, 24 months
measure: body composition
timeFrame: 0, 24 months
measure: blood pressure
timeFrame: 0,12,24 months
measure: number of teeth
timeFrame: 0, 24 months
measure: cost, health care utilization
timeFrame: 0,6,12,18,24 months
measure: facial skin keratosis (number and size)
timeFrame: 0, 24 months
measure: cognitive function
timeFrame: 0, 24 months
measure: depression, mental health
timeFrame: 0,12,24 months
measure: fasting blood glucose - insulin levels
timeFrame: 0,12,24
measure: Number of upper respiratory infections and number of any infections
timeFrame: 0, 6,12,28,24
measure: bone metabolism
timeFrame: 0,6,12,18,24
measure: radiographic progression of the non-operated knee
timeFrame: 0, 24 months
measure: general pain
timeFrame: 0,6,12,18,24 months
measure: Quality of life
timeFrame: 0,6,12,18,24
Other outcomes:
Locations:
city: Zurich
country: Switzerland
facility: University Hospital Zurich, Centre on Aging and Mobility
state: ZH
Study officials:
affiliation: University Hospital Zurich, Centre on Aging and Mobility
name: Heike Bischoff-Ferrari, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Abderhalden LA, Meyer S, Dawson-Hughes B, Orav EJ, Meyer U, de Godoi Rezende Costa Molino C, Theiler R, Stahelin HB, Ruschitzka F, Egli A, Forman JP, Willett WC, Bischoff-Ferrari HA. Effect of daily 2000 IU versus 800 IU vitamin D on blood pressure among adults age 60 years and older: a randomized clinical trial. Am J Clin Nutr. 2020 Sep 1;112(3):527-537. doi: 10.1093/ajcn/nqaa145.
citation: Freystaetter G, Fischer K, Orav EJ, Egli A, Theiler R, Munzer T, Felson DT, Bischoff-Ferrari HA. Total Serum Testosterone and Western Ontario and McMaster Universities Osteoarthritis Index Pain and Function Among Older Men and Women With Severe Knee Osteoarthritis. Arthritis Care Res (Hoboken). 2020 Nov;72(11):1511-1518. doi: 10.1002/acr.24074.
citation: Schietzel S, Fischer K, Brugger P, Orav EJ, Renerts K, Gagesch M, Freystaetter G, Stahelin HB, Egli A, Bischoff-Ferrari HA. Effect of 2000 IU compared with 800 IU vitamin D on cognitive performance among adults age 60 years and older: a randomized controlled trial. Am J Clin Nutr. 2019 Jul 1;110(1):246-253. doi: 10.1093/ajcn/nqz081.