Vitamin D to Slow Progression of Knee Osteoarthritis

Tufts University

Status and phase: Completed; Phase 2

Conditions: Osteoarthritis, Knee

Treatments: Dietary Supplement: Vitamin D (cholecalciferol); Dietary Supplement: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00306774

R01AR051361 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 146 patients

Sex: All

Ages: 45 to 90 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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146 participants in 2 patient groups, including a placebo group

1

Experimental group

Description:

Participants will receive vitamin D (cholecalciferol)

Treatment:

Dietary Supplement: Vitamin D (cholecalciferol)

2

Placebo Comparator group

Description:

Participants will receive a matched placebo

Treatment:

Dietary Supplement: Placebo