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VItamin D Effect on Osteoarthritis Study (VIDEO)

Primary Purpose

Osteoarthritis, Knee

Status
Completed
Phase
Phase 3
Locations
Australia
Study Type
Interventional
Intervention
Vitamin D
Placebo
Sponsored by
Menzies Institute for Medical Research
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Osteoarthritis, Knee focused on measuring Vitamin D supplementation, Osteoarthritis, Knee, Randomised clinical trial (RCT), Cartilage, MRI

Eligibility Criteria

50 Years - 79 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Menzies Research Institute, University of Tasmania
  • Department of Epidemiology & Preventive Medicine, Monash University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Vitamin D supplementation

Placebo

Arm Description

Participants in the intervention arm will receive 50,000 IU (1.25 mg) cholecalciferol capsules given once monthly

The control arm will receive identical inert placebo capsules given once monthly.

Outcomes

Primary Outcome Measures

Loss of knee cartilage volume
Cartilage volume will be assessed using magnetic resonance imaging (MRI)
Change in knee pain
Assessed using WOMAC

Secondary Outcome Measures

Progression of knee cartilage defects
Knee cartilage defects will be measured using MRI.
Change in bone marrow lesions
Assessed using MRI
Change in knee pain
Assessed using VAS
Change in physical function
Assessed using WOMAC function
Change in joint effusion
Assessed using MRI
Central blood pressure
Radial applanation tonometry
Aortic stiffness
Carotid to femoral pulse wave velocity

Full Information

First Posted
August 4, 2010
Last Updated
September 7, 2015
Sponsor
Menzies Institute for Medical Research
Collaborators
Monash University
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1. Study Identification

Unique Protocol Identification Number
NCT01176344
Brief Title
VItamin D Effect on Osteoarthritis Study
Acronym
VIDEO
Official Title
Does Vitamin D Supplementation Prevent Progression of Knee Osteoarthritis? A Randomised Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
September 2015
Overall Recruitment Status
Completed
Study Start Date
August 2010 (undefined)
Primary Completion Date
December 2013 (Actual)
Study Completion Date
December 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Menzies Institute for Medical Research
Collaborators
Monash University

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteoarthritis, Knee
Keywords
Vitamin D supplementation, Osteoarthritis, Knee, Randomised clinical trial (RCT), Cartilage, MRI

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
413 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Vitamin D supplementation
Arm Type
Experimental
Arm Description
Participants in the intervention arm will receive 50,000 IU (1.25 mg) cholecalciferol capsules given once monthly
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
The control arm will receive identical inert placebo capsules given once monthly.
Intervention Type
Drug
Intervention Name(s)
Vitamin D
Intervention Description
50,000 IU (1.25 mg) cholecalciferol capsules once monthly for 2 years
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Inert placebo capsules once monthly for 2 years.
Primary Outcome Measure Information:
Title
Loss of knee cartilage volume
Description
Cartilage volume will be assessed using magnetic resonance imaging (MRI)
Time Frame
Over 2 years (Cartilage volume will be assessed at baseline and 2 years later)
Title
Change in knee pain
Description
Assessed using WOMAC
Time Frame
Over 2 years
Secondary Outcome Measure Information:
Title
Progression of knee cartilage defects
Description
Knee cartilage defects will be measured using MRI.
Time Frame
Over 2 years (Cartilahe defects will be measured at baseline and 2 years later)
Title
Change in bone marrow lesions
Description
Assessed using MRI
Time Frame
Over 2 years
Title
Change in knee pain
Description
Assessed using VAS
Time Frame
Over 2 years
Title
Change in physical function
Description
Assessed using WOMAC function
Time Frame
Over 2 years
Title
Change in joint effusion
Description
Assessed using MRI
Time Frame
Over 2 years
Title
Central blood pressure
Description
Radial applanation tonometry
Time Frame
one year
Title
Aortic stiffness
Description
Carotid to femoral pulse wave velocity
Time Frame
one year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age 50-79 years old; 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; Have an American College of Rheumatology (ACR) functional class rating of I, II and III; 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]); Have serum vitamin D level of >12.5 nmol/L and <60 nmol/L; Are able to read, speak and understand English, capable of understanding the study requirements and willing to co-operate with the study instructions; Are able and willing to give informed consent; Are willing and able to give blood samples; Are willing and able to have knee MRIs performed Exclusion Criteria: Have Grade 3 radiographic changes in their knee which is to be investigated; Have severe knee pain (more than 80 mm on a 100-mm visual analogue scale,VAS) in most days of the last month; Have any contra-indications for having MRIs scans performed; 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; Have ever had knee joint replacement; Have anticipated need for knee or hip surgery in the next 2 years; Have any stomach or intestinal condition possibly affecting oral drug absorption; 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Changhai Ding, MD
Organizational Affiliation
Menzies Research Institute & Monash University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Graeme Jones, MD
Organizational Affiliation
Menzies Institute for Medical Research
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Flavia M Cicuttini, PhD
Organizational Affiliation
Monash University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Menzies Research Institute, University of Tasmania
City
Hobart
State/Province
Tasmania
ZIP/Postal Code
7000
Country
Australia
Facility Name
Department of Epidemiology & Preventive Medicine, Monash University
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia

12. IPD Sharing Statement

Citations:
PubMed Identifier
19404958
Citation
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.
Results Reference
background
PubMed Identifier
35086561
Citation
Chang J, Chen T, Yan Y, Zhu Z, Han W, Zhao Y, Antony B, Wluka A, Winzenberg T, Cicuttini F, Ding C. Associations between the morphological parameters of proximal tibiofibular joint (PTFJ) and changes in tibiofemoral joint structures in patients with knee osteoarthritis. Arthritis Res Ther. 2022 Jan 27;24(1):34. doi: 10.1186/s13075-022-02719-8.
Results Reference
derived
PubMed Identifier
33413273
Citation
Zheng S, Tu L, Cicuttini F, Zhu Z, Han W, Antony B, Wluka AE, Winzenberg T, Aitken D, Blizzard L, Jones G, Ding C. Depression in patients with knee osteoarthritis: risk factors and associations with joint symptoms. BMC Musculoskelet Disord. 2021 Jan 7;22(1):40. doi: 10.1186/s12891-020-03875-1.
Results Reference
derived
PubMed Identifier
32623812
Citation
Tu L, Zheng S, Cicuttini F, Jin X, Han W, Zhu Z, Antony B, Winzenberg T, Jones G, Gu J, Wluka AE, Ding C. Effects of Vitamin D Supplementation on Disabling Foot Pain in Patients With Symptomatic Knee Osteoarthritis. Arthritis Care Res (Hoboken). 2021 Jun;73(6):781-787. doi: 10.1002/acr.24371.
Results Reference
derived
PubMed Identifier
30565892
Citation
Cuellar WA, Blizzard L, Hides JA, Callisaya ML, Jones G, Cicuttini F, Wluka AE, Ding C, Winzenberg TM. Vitamin D supplements for trunk muscle morphology in older adults: secondary analysis of a randomized controlled trial. J Cachexia Sarcopenia Muscle. 2019 Feb;10(1):177-187. doi: 10.1002/jcsm.12364. Epub 2018 Nov 22.
Results Reference
derived
PubMed Identifier
28864651
Citation
Wang X, Jin X, Blizzard L, Antony B, Han W, Zhu Z, Cicuttini F, Wluka AE, Winzenberg T, Jones G, Ding C. Associations Between Knee Effusion-synovitis and Joint Structural Changes in Patients with Knee Osteoarthritis. J Rheumatol. 2017 Nov;44(11):1644-1651. doi: 10.3899/jrheum.161596. Epub 2017 Sep 1.
Results Reference
derived
PubMed Identifier
27836676
Citation
Zhu Z, Otahal P, Wang B, Jin X, Laslett LL, Wluka AE, Antony B, Han W, Wang X, Winzenberg T, Cicuttini F, Jones G, Ding C. Cross-sectional and longitudinal associations between serum inflammatory cytokines and knee bone marrow lesions in patients with knee osteoarthritis. Osteoarthritis Cartilage. 2017 Apr;25(4):499-505. doi: 10.1016/j.joca.2016.10.024. Epub 2016 Nov 9.
Results Reference
derived
PubMed Identifier
26954409
Citation
Jin X, Jones G, Cicuttini F, Wluka A, Zhu Z, Han W, Antony B, Wang X, Winzenberg T, Blizzard L, Ding C. Effect of Vitamin D Supplementation on Tibial Cartilage Volume and Knee Pain Among Patients With Symptomatic Knee Osteoarthritis: A Randomized Clinical Trial. JAMA. 2016 Mar 8;315(10):1005-13. doi: 10.1001/jama.2016.1961.
Results Reference
derived
PubMed Identifier
26748954
Citation
Zhu Z, Jin X, Wang B, Wluka A, Antony B, Laslett LL, Winzenberg T, Cicuttini F, Jones G, Ding C. Cross-Sectional and Longitudinal Associations Between Serum Levels of High-Sensitivity C-Reactive Protein, Knee Bone Marrow Lesions, and Knee Pain in Patients With Knee Osteoarthritis. Arthritis Care Res (Hoboken). 2016 Oct;68(10):1471-7. doi: 10.1002/acr.22834. Epub 2016 Sep 6.
Results Reference
derived
PubMed Identifier
26670070
Citation
Veloudi P, Blizzard CL, Ding CH, Cicuttini FM, Jin X, Wluka AE, Winzenberg T, Jones G, Sharman JE. Effect of Vitamin D Supplementation on Aortic Stiffness and Arterial Hemodynamics in People With Osteoarthritis and Vitamin D Deficiency. J Am Coll Cardiol. 2015 Dec 15;66(23):2679-2681. doi: 10.1016/j.jacc.2015.10.007. No abstract available.
Results Reference
derived
PubMed Identifier
22867111
Citation
Cao Y, Jones G, Cicuttini F, Winzenberg T, Wluka A, Sharman J, Nguo K, Ding C. Vitamin D supplementation in the management of knee osteoarthritis: study protocol for a randomized controlled trial. Trials. 2012 Aug 6;13:131. doi: 10.1186/1745-6215-13-131.
Results Reference
derived
Links:
URL
http://www.menzies.utas.edu.au/information.php?Doo=ViewData&type=Project&ID=173
Description
The Vitamin D Effect on Osteoarthritis (VIDEO) Study: a randomised controlled trial

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VItamin D Effect on Osteoarthritis Study

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