VItamin D Effect on Osteoarthritis Study (VIDEO)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2012 by Menzies Research Institute Tasmania.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Monash University
Information provided by:
Menzies Research Institute Tasmania
ClinicalTrials.gov Identifier:
NCT01176344
First received: August 4, 2010
Last updated: April 19, 2012
Last verified: April 2012
  Purpose

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 slow knee cartilage loss in OA patients comparing with a placebo. Use of MRI will provide sensitive measures of knee OA changes.


Condition Intervention Phase
Osteoarthritis, Knee
Drug: Vitamin D
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Does Vitamin D Supplementation Prevent Progression of Knee Osteoarthritis? A Randomised Controlled Trial

Resource links provided by NLM:


Further study details as provided by Menzies Research Institute Tasmania:

Primary Outcome Measures:
  • Loss of knee cartilage volume [ Time Frame: Over 2 years (Cartilage volume will be assessed at baseline and 2 years later) ] [ Designated as safety issue: No ]
    Cartilage volume will be assessed using magnetic resonance imaging (MRI)


Secondary Outcome Measures:
  • Progression of knee cartilage defects [ Time Frame: Over 2 years (Cartilahe defects will be measured at baseline and 2 years later) ] [ Designated as safety issue: No ]
    Knee cartilage defects will be measured using MRI.

  • Loss of limb muscle strength [ Time Frame: Over 2 years (limb muscle strength will be assessed at at baseline and 2 years later) ] [ Designated as safety issue: No ]
  • Enlargement of tibial bone area [ Time Frame: Over 2 years (Tibial bone area will be assessed at baseline and 2 years later) ] [ Designated as safety issue: No ]
    Tibial bone area will be measured using MRI

  • Central blood pressure [ Time Frame: one year ] [ Designated as safety issue: No ]
    Radial applanation tonometry

  • Aortic stiffness [ Time Frame: one year ] [ Designated as safety issue: No ]
    Carotid to femoral pulse wave velocity


Estimated Enrollment: 400
Study Start Date: August 2010
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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 structural changes and lower limb muscle strength 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 lower limb muscle strength at baseline and 2 years later will be determined as outcome measures. Other explanatory factors, such as serum vitamin D levels, knee pain, 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, and meniscus) 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.

  Eligibility

Ages Eligible for Study:   50 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01176344

Locations
Australia, Tasmania
Menzies Research Institute, University of Tasmania
Hobart, Tasmania, Australia, 7000
Australia, Victoria
Department of Epidemiology & Preventive Medicine, Monash University
Melbourne, Victoria, Australia, 3004
Sponsors and Collaborators
Menzies Research Institute Tasmania
Monash University
Investigators
Principal Investigator: Changhai Ding, MD Menzies Research Institute & Monash University
Principal Investigator: Graeme Jones, MD Menzies Research Institute Tasmania
Principal Investigator: Flavia M Cicuttini, PhD Monash University
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Associate Professor Changhai Ding, Menzies Research Institute
ClinicalTrials.gov Identifier: NCT01176344     History of Changes
Other Study ID Numbers: VIDEO605501
Study First Received: August 4, 2010
Last Updated: April 19, 2012
Health Authority: Australia: National Health and Medical Research Council
Australia: Human Research Ethics Committee

Keywords provided by Menzies Research Institute Tasmania:
Vitamin D supplementation
Osteoarthritis
Knee
Randomised clinical trial (RCT)
Cartilage
MRI

Additional relevant MeSH terms:
Osteoarthritis
Osteoarthritis, Knee
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Vitamin D
Ergocalciferols
Vitamins
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on July 26, 2014