VItamin D Effect on Osteoarthritis Study (VIDEO)

September 7, 2015 updated by: Changhai Ding, Menzies Institute for Medical Research

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

413

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Tasmania
      • Hobart, Tasmania, Australia, 7000
        • Menzies Research Institute, University of Tasmania
    • Victoria
      • Melbourne, Victoria, Australia, 3004
        • Department of Epidemiology & Preventive Medicine, Monash University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years to 79 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Vitamin D supplementation
Participants in the intervention arm will receive 50,000 IU (1.25 mg) cholecalciferol capsules given once monthly
Drug: Vitamin D
50,000 IU (1.25 mg) cholecalciferol capsules once monthly for 2 years
Placebo Comparator: Placebo
The control arm will receive identical inert placebo capsules given once monthly.
Drug: Placebo
Inert placebo capsules once monthly for 2 years.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Loss of knee cartilage volume
Time Frame: Over 2 years (Cartilage volume will be assessed at baseline and 2 years later)
Cartilage volume will be assessed using magnetic resonance imaging (MRI)
Over 2 years (Cartilage volume will be assessed at baseline and 2 years later)
Change in knee pain
Time Frame: Over 2 years
Assessed using WOMAC
Over 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression of knee cartilage defects
Time Frame: Over 2 years (Cartilahe defects will be measured at baseline and 2 years later)
Knee cartilage defects will be measured using MRI.
Over 2 years (Cartilahe defects will be measured at baseline and 2 years later)
Change in bone marrow lesions
Time Frame: Over 2 years
Assessed using MRI
Over 2 years
Change in knee pain
Time Frame: Over 2 years
Assessed using VAS
Over 2 years
Change in physical function
Time Frame: Over 2 years
Assessed using WOMAC function
Over 2 years
Change in joint effusion
Time Frame: Over 2 years
Assessed using MRI
Over 2 years
Central blood pressure
Time Frame: one year
Radial applanation tonometry
one year
Aortic stiffness
Time Frame: one year
Carotid to femoral pulse wave velocity
one year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Menzies Institute for Medical Research

Collaborators

Monash University

Investigators

  • Principal Investigator: Changhai Ding, MD, Menzies Research Institute & Monash University
  • Principal Investigator: Graeme Jones, MD, Menzies Institute for Medical Research
  • Principal Investigator: Flavia M Cicuttini, PhD, Monash University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2010

Primary Completion (Actual)

December 1, 2013

Study Completion (Actual)

December 1, 2014

Study Registration Dates

First Submitted

August 4, 2010

First Submitted That Met QC Criteria

August 5, 2010

First Posted (Estimate)

August 6, 2010

Study Record Updates

Last Update Posted (Estimate)

September 9, 2015

Last Update Submitted That Met QC Criteria

September 7, 2015

Last Verified

September 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VIDEO605501

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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