VItamin D Effect on Osteoarthritis Study

Osteoarthritis, Knee Clinical Trial

— VIDEO  

Official title:

Does Vitamin D Supplementation Prevent Progression of Knee Osteoarthritis? A Randomised Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01176344
• Other study ID #: VIDEO605501
• Status: Completed
• Phase: Phase 3
• First received: August 4, 2010
• Last updated: September 7, 2015
• Start date: August 2010
• Est. completion date: December 2014

Study information

• Verified date: September 2015
• Source: Menzies Institute for Medical Research
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: National Health and Medical Research CouncilAustralia: Human Research Ethics Committee
• Study type: Interventional

Clinical Trial Summary

Observational evidence suggests that vitamin D deficiency may have a role in the causes of osteoarthritis (OA) and there are biologically plausible mechanisms to explain this. There is, however, no evidence which shows that intervening with vitamin D supplementation can slow the progression of OA. This study is to determine if vitamin D supplementation can reduce knee pain and slow knee cartilage loss in OA patients comparing with a placebo. Use of MRI will provide sensitive measures of knee OA changes.

Description:

Osteoarthritis (OA) is the most common joint disorder in the world. In 2004, OA was estimated to affect over 1.6 million Australians, with total costs of $1.4 billion. OA is the most frequent reason for joint replacement, at a cost of about $1 billion each year. Conventional treatment is palliative and costly, and currently there are no effective medical remedies for OA. These facts have led to 2000-2010 being labelled the Bone and Joint decade, and musculoskeletal disorders being recognised as a National Health Priority. The primary task for OA management should be to identify modifiable risk factors.

Vitamin D deficiency is very common in older people and has been linked with osteoporosis and falls in both older women and men. Emerging data suggests that it also plays an important role in the pathogenesis of knee OA. Firstly, vitamin D may have direct effects on chondrocytes in osteoarthritic cartilage; secondly, chronic vitamin D inadequacy in adults has adverse effects on calcium metabolism, osteoblast activity, matrix ossification and bone density, and thus could impair the ability of bone to respond optimally to pathophysiological processes in OA; and thirdly, low vitamin D levels are associated with loss of muscle strength and muscle mass in older men and women, which may be associated with an increased risk of knee OA. Some observational studies have shown that vitamin D insufficiency is associated with the progression and development of radiographic knee or hip OA. Recently we have demonstrated that baseline serum levels of 25-hydroxy-vitamin D(25-(OH)D) predicts change in cartilage volume in older adults over 2 years, and increases in vitamin D levels are associated with a further protective association. This suggests that vitamin D supplementation may enhance cartilage and bone health, and thus prevent disease progression in patients with knee OA.

The aim of this study is to compare the effects of vitamin D supplementation versus placebo on knee pain and knee structural changes in patients with symptomatic knee osteoarthritis over a 2- year period.

The proposed study design is a randomised, placebo-controlled, double-blind clinical trial. We will recruit 400 subjects (50-79 years old, having relatively good health and serum vitamin D level of <60 and >12.5 nmol/L) with symptomatic knee OA for at least 6 months using a combined strategy in Southern Tasmania and Melbourne. Participants in the intervention arm (n=200) will receive 50,000 IU (1.25 mg) cholecalciferol tablets given once monthly, whilst those in the control arm (n=200) will receive an identical inert placebo. All participants will be provided recommended standard of care. Knee structural changes including knee cartilage volume, cartilage defects, tibial bone area, bone marrow lesions, and meniscal pathology (assessed by MRI), and knee pain at baseline and 2 years later will be determined as outcome measures. Other explanatory factors, such as serum vitamin D levels, height, weight, physical activity, and smoking will also be determined through study period.

Significance:

Observational evidence suggests that vitamin D deficiency may have a role in the progression of OA and there are biologically plausible mechanisms to explain this. However, randomized controlled trials using a sensitive method are required to determine whether intervening with vitamin D supplementation can in fact slow the progression of this disease. In this study, the randomized, placebo-controlled, double-blind design, and the use of MRI to provide sensitive and precise measures of knee structural change will ensure a rigorous evaluation of the impact of vitamin D supplementation on knee OA. It will be the first long term clinical trial to determine comprehensively the effects on knee structural changes (cartilage, bone) utilizing the pioneering MRI techniques and limb muscle strength assessment. This study builds upon previous clinical and epidemiological studies that supports the objectives of the Bone and Joint Decade organization and addresses a National Health Priority Area.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 413
• Est. completion date: December 2014
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years to 79 Years

Eligibility

Inclusion Criteria:

1. Age 50-79 years old;

2. Men and women with symptomatic knee osteoarthritis (OA) with a pain visual analogue scale (VAS) of at least 20 mm in most days of the last month;

3. Have an American College of Rheumatology (ACR) functional class rating of I, II and III;

4. Have relatively good health (0-2 according to the investigator's global assessment of disease status on a 5-point Likert scale, range 0 [very well] to 4 [very poor]);

5. Have serum vitamin D level of >12.5 nmol/L and <60 nmol/L;

6. Are able to read, speak and understand English, capable of understanding the study requirements and willing to co-operate with the study instructions;

7. Are able and willing to give informed consent;

8. Are willing and able to give blood samples;

9. Are willing and able to have knee MRIs performed

Exclusion Criteria:

1. Have Grade 3 radiographic changes in their knee which is to be investigated;

2. Have severe knee pain (more than 80 mm on a 100-mm visual analogue scale,VAS) in most days of the last month;

3. Have any contra-indications for having MRIs scans performed;

4. Have had significant trauma to the knees including arthroscopy or significant injury to ligaments or menisci of the knee within 1 year preceding the screening visit;

5. Have ever had knee joint replacement;

6. Have anticipated need for knee or hip surgery in the next 2 years;

7. Have any stomach or intestinal condition possibly affecting oral drug absorption;

8. Have any clinically significant condition(s) such as (but not limited to) rheumatoid arthritis, psoriatic arthritis, lupus, active cancer, cardiac or renal function impairment or hypersensitivity to vitamin D that in the opinion of the investigator may compromise their safety or compliance, interfere with evaluation or preclude completion of the study.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Drug:
• Vitamin D
50,000 IU (1.25 mg) cholecalciferol capsules once monthly for 2 years
• Placebo
Inert placebo capsules once monthly for 2 years.

Locations

Country	Name	City	State
Australia	Menzies Research Institute, University of Tasmania	Hobart	Tasmania
Australia	Department of Epidemiology & Preventive Medicine, Monash University	Melbourne	Victoria

Sponsors (2)

Lead Sponsor	Collaborator
Menzies Institute for Medical Research	Monash University

Country where clinical trial is conducted

Australia, 

References & Publications (1)

Ding C, Cicuttini F, Parameswaran V, Burgess J, Quinn S, Jones G. Serum levels of vitamin D, sunlight exposure, and knee cartilage loss in older adults: the Tasmanian older adult cohort study. Arthritis Rheum. 2009 May;60(5):1381-9. doi: 10.1002/art.24486. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Loss of knee cartilage volume	Cartilage volume will be assessed using magnetic resonance imaging (MRI)	Over 2 years (Cartilage volume will be assessed at baseline and 2 years later)	No
Primary	Change in knee pain	Assessed using WOMAC	Over 2 years	No
Secondary	Progression of knee cartilage defects	Knee cartilage defects will be measured using MRI.	Over 2 years (Cartilahe defects will be measured at baseline and 2 years later)	No
Secondary	Change in bone marrow lesions	Assessed using MRI	Over 2 years	No
Secondary	Change in knee pain	Assessed using VAS	Over 2 years	No
Secondary	Change in physical function	Assessed using WOMAC function	Over 2 years	No
Secondary	Change in joint effusion	Assessed using MRI	Over 2 years	No
Secondary	Central blood pressure	Radial applanation tonometry	one year	No
Secondary	Aortic stiffness	Carotid to femoral pulse wave velocity	one year	No

External Links

•   The Vitamin D Effect on Osteoarthritis (VIDEO) Study: a randomised controlled trial