Vitamin D to Slow Progression of Knee Osteoarthritis

NCT ID: NCT00306774

Last Updated: 2011-09-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 146 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-03-31
• Study Completion Date: 2009-06-30

Brief 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.

Detailed 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.

Conditions

Osteoarthritis, Knee

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1

Participants will receive vitamin D (cholecalciferol)

Group Type: EXPERIMENTAL

Vitamin D (cholecalciferol)

Intervention Type: DIETARY_SUPPLEMENT

2,000 IU vitamin D capsule per day for 2 years

2

Participants will receive a matched placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DIETARY_SUPPLEMENT

Placebo capsule per day for 2 years

Interventions

Vitamin D (cholecalciferol)

2,000 IU vitamin D capsule per day for 2 years

Intervention Type: DIETARY_SUPPLEMENT

Placebo

Placebo capsule per day for 2 years

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

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

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

NIH

Sponsor Role: collaborator

Office of Dietary Supplements (ODS)

NIH

Sponsor Role: collaborator

Tufts Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Timothy E. McAlindon, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Tufts Medical Center

Locations

Tufts Medical Center, Division of Rheumatology

Boston, Massachusetts, United States

Countries

United States

References

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 (KOA). ACR Abstract #199 Arthritis & Rheumatism. 2007;56: 9 (supplement): S124.

Reference Type: RESULT

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 #2049 Arthritis & Rheumatism. 2007;56: 9 (supplement): S779.

Reference Type: RESULT

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 Osteoarthritis Patients. OARSI Abstract #248 Osteoarthritis and Cartilage. 2007. Vol. 15 (Supplement A)

Reference Type: RESULT

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.

Reference Type: RESULT

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 Arthritis & Rheumatism. 2008.

Reference Type: RESULT

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 Osteoarthritis (KOA). ACR Abstract #697 Arthritis & Rheumatism. 2008.

Reference Type: RESULT

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 Cartilage. 2008. Vol. 16 (Supplement 4)

Reference Type: RESULT

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 Orthopaedic Research Society (ORS), Las Vegas, Feb. 2009.

Reference Type: RESULT

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

Reference Type: RESULT

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

Reference Type: RESULT

McAlindon T, LaValley M, Schneider E, Nuite M, Lee JY, Price LL, Lo G, Dawson-Hughes B. Effect of vitamin D supplementation on progression of knee pain and cartilage volume loss in patients with symptomatic osteoarthritis: a randomized controlled trial. JAMA. 2013 Jan 9;309(2):155-62. doi: 10.1001/jama.2012.164487.

Reference Type: DERIVED

PMID: 23299607 (View on PubMed)

Lo GH, Harvey WF, McAlindon TE. Associations of varus thrust and alignment with pain in knee osteoarthritis. Arthritis Rheum. 2012 Jul;64(7):2252-9. doi: 10.1002/art.34422.

Reference Type: DERIVED

PMID: 22307813 (View on PubMed)

Other Identifiers

R01AR051361

Identifier Type: NIH

Identifier Source: secondary_id

View Link

R01AR051361

Identifier Type: NIH

Identifier Source: org_study_id

View Link