Vitamin D to Slow Progression of Knee Osteoarthritis

Osteoarthritis, Knee Clinical Trial

Official title:

Trial of Vitamin D to Reduce the Progression of Knee Osteoarthritis: A Double-Blind, Placebo-Controlled Once Daily Dosing Regimen

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00306774
• Other study ID #: R01AR051361
• Secondary ID: R01AR051361
• Status: Completed
• Phase: Phase 2
• First received: March 22, 2006
• Last updated: September 21, 2011
• Start date: March 2006
• Est. completion date: June 2009

Study information

• Verified date: September 2011
• Source: Tufts Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

Knee osteoarthritis (OA) is a common and disabling health problem in older adults and for which there is no cure. The purpose of this study is to determine the effects of vitamin D on knee OA symptoms and physical function in adults aged 45 years and older.

Description:

Symptomatic knee OA is one of the most frequent causes of limitation in lower limb tasks, especially in the elderly. Knee OA causes 68 million lost work days per year. OA is the most frequent reason for joint replacement, at a cost of billions of dollars per year. There are currently no completely effective medical remedies for OA. Pharmaceutical companies are trying to develop drugs that will slow the disease progression of OA; however, such medications will be expensive to use in a population in which OA is common. There is evidence that vitamin D supplementation, a simple and much cheaper intervention, may prove useful in slowing the progression of OA. Even if only modestly effective, it could have considerable impact in terms of reducing the societal burden of OA. Therefore, in the interests of public health, the efficacy of vitamin D supplementation as a disease-modifying treatment for OA needs to be tested in a rigorous clinical trial. Disease modification trials for knee OA have been difficult in the past due to limitations of radiographic techniques. Fortunately, magnetic resonance imaging (MRI) has emerged as a valid, precise, and reproducible tool for the measurement of damage of cartilage and joint structures. The purpose of this study is to evaluate the effects of vitamin D on knee OA symptoms and physical function in older adults.

Patients with symptomatic knee OA will be randomly assigned to receive vitamin D at 2,000 International Units (IU) a day or placebo. Each participant will be in the study for about 2 years. During that time, there will be 9 scheduled study visits (screening, Months 0, 2, 4, 8, 12, 16, 20, and 24) and interim safety visits as needed. Measurements of vital signs, a knee exam, blood and urine collection, pill counts, and completion of questionnaires will occur at all visits. Participants' physical function will be assessed at study entry and Months 0, 12, and 24. MRI, bone density scanning, and an assessment by the study staff will occur at Months 0, 12, and 24. Knee x-rays will occur at study screening and Month 24.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 146
• Est. completion date: June 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 45 Years to 90 Years

Eligibility

Inclusion Criteria:

• Chronic knee discomfort based on affirmative response to the question "During the past 12 months, have you had pain, aching, or stiffness in or around your knee(s) on most days for at least one month?"

• WOMAC pain subscale score of at least 1

• Tibiofemoral OA on posterior anterior (PA) weight-bearing semi-flexed knee radiographs with severity equivalent to Kellgren and Lawrence grade of at least 2

• Clinical examination confirming knee pain or discomfort referable to the knee joint

• Prepared to refrain from use of glucosamine, chondroitin, MSM, DMSO, and doxycycline

• Pass faintness of heart trial period

Exclusion Criteria:

• Serum 25(OH) vitamin D level greater than 80 ng/ml

• Use of glucosamine, chondroitin, or doxycycline within 3 months of random assignment

• Use of MSM, DMSO within 3 months of random assignment

• Use of vitamin D supplements such that the total daily dose is greater than 1,000 IU or a single source is greater than 800 IU

• Intra-articular joint injections (e.g., glucocorticoid or haluronic acid formulations, within 3 months of random assignment)

• Chronic glucocorticoid use

• Hypercalcemia (total serum calcium greater than 10.5 mg/dL)

• Hypercalcuria (spot urine calcium: creatinine ratio of 0.275 for women and 0.325 for men, corresponding to 24-hour calcium excretion of 0.30 and 0.35 g, respectively)

• Estimated GFR less than 30

• Hyperparathyroidism (PTH greater than 65 pg/mL)

• History of lymphoma or sarcoidosis

• Reiter's syndrome

• Psoriatic arthritis

• Rheumatoid arthritis

• Ankylosing spondylitis

• Currently on treatment for tuberculosis

• Malabsorption disorders (e.g., advance liver disease, chronic renal disease-stage 4 or 5, Crohn's disease, Whipple's disease, celiac sprue)

• Serious medical conditions or impairments that, in the view of the investigator, would obstruct study participation

• Pregnancy

• Plan to permanently relocate from the region during the trial period

• Planned knee or hip arthroplasty during the study period

• Any contra-indication to having an MRI scan

Study Design

Allocation: Randomized, Endpoint Classification: 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

Dietary Supplement:
• Vitamin D (cholecalciferol)
2,000 IU vitamin D capsule per day for 2 years
• Placebo
Placebo capsule per day for 2 years

Locations

Country	Name	City	State
United States	Tufts Medical Center, Division of Rheumatology	Boston	Massachusetts

Sponsors (3)

Lead Sponsor	Collaborator
Tufts Medical Center	National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), Office of Dietary Supplements (ODS)

Country where clinical trial is conducted

United States, 

References & Publications (10)

E.L. McAdams, G.H. Lo, L.L. Price, M.H. Smith, K.A. Carr, M. Nuite, J.P. Joas, T.E. McAlindon. Varus-Valgus Static Malalignment does Not Predict Changes in Physical Function over a 1-year Period in People with Knee Osteoarthritis (OA). ACR Abstract #194 A

G.H. Lo, M.H. Smith, E.L. McAdams, K.A. Carr, M. Nuite, B. Dawson-Hughes, N. Palermo, T.E. McAlindon. Baseline Vitamin D Status is Predictive of Longitudinal Change in Tibial BMD in Knee Osteoarthritis (OA). ACR Abstract #193 Arthritis & Rheumatism. 2008.

Grace H. Lo, Timothy E. McAlindon, Kimberly A. Carr, Melanie A. Ripley, Melynn Nuite, William F. Harvey. Varus Thrust Is Associated with Pain in Knee Osteoarthritis. Arthritis and Rheumatism. 2009; 60:10(supplement) S310, Abstract #831

Hansberry S., Lo G., Carr K., McAlindon T., Ward R., Nuite M., Schneider E. Comparing Quantitative v. Semi-Quantitative Analysis of Cartilage Degradation and Its Association with Knee Pain. Poster # 1072 from Transactions of the 55th Annual Meeting of the

L. M. Wheeler, J. Wang, M. Nuite, J. Fletcher, P. Badiani, E. L. McAdams, J. P. Joas, M. P. LaValley, B. Dawson-Hughes, T. E. McAlindon. Report of Daily Vitamin D Supplement Use is No Guarantee of Protection Against Vitamin D Deficiency in Knee Osteoarthr

Lo G.H., McAdams E., Smith M., Carr K., Nuite M., Dawson-Hughes B., Palermo N., McAlindon T.E. Tibial Plateau Proximal and Distal Bone Behave Similarly: Both Are Associated with Features of Knee Osteoarthritis (KOA). OARSI Abstract #137 Osteoarthritis and

M.H. Smith, G.H. Lo, M. Nuite, E.L. McAdams, K.A. Carr, J.P. Joas, B. Dawson-Hughes, N. Palermo, T.E. McAlindon. Increased Medial Tibial Bone Mineral Density (BMD) is Associated with Deterioration in Walking Ability and Pain in Individuals with Knee Osteo

Nuite, M., Wang, J., Wheeler, L.M., Fletcher, J., Badiani, P., McAdams, E.L., Joas, J., LaValley, M.P., Dawson-Hughes, B., McAlindon, T.E. Don't Always Believe What You Are Told: A comparison of Self-Reported with Measured Weight and Height. ARHP Abstract

W.F. Harvey, J.Y. Lee, K.A. Carr, M.A. Ripley, M. Nuite, T. E. McAlindon, G.H. Lo. Varus Thrust Is Associated with Cartilage Loss in Knee Osteoarthritis. Arthritis and Rheumatism. 2009; 60:10(supplement) S77, Abstract #211

Wang, J., Nuite, M., Wheeler, L.M., Badiani, P., Joas, J., McAdams, E.L., Fletcher, J., LaValley, M.P., Dawson-Hughes, B., McAlindon, T.E. Low Vitamin D Levels are Associated with Greater Pain and Slow Walking Speed in Patients with Knee Osteoarthritis (K

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cartilage volume loss (MRI)		2 years	No
Primary	Knee symptoms (WOMAC questionnaire)		2 years	No
Secondary	Physical function		2 years	No
Secondary	Quality of life		2 years	No
Secondary	Pathological (MRI) severity global score		2 years	No