Vitamin D Deficiency Causes Immune Dysfunction and Enables or Perpetuates the Development of Rheumatoid Arthritis
|Arthritis, Rheumatoid Vitamin D Deficiency||Drug: Placebo in arm A and Vitamin D in arm B Drug: vitamin D 3 for arm A ,and matching placebo for arm B||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Vitamin D Deficiency Causes Immune Dysfunction and Enables or Perpetuates the Development of Rheumatoid Arthritis: Clinical Trial and Investigations on Dendritic Cells|
- ACR20 [ Time Frame: Baseline and every 2 months for 6 months ]
- Changes in surface marker expression of blood myeloid dendritic cells [ Time Frame: Baseline and at completion of study on the 6th month ]
|Study Start Date:||May 2009|
|Estimated Study Completion Date:||May 2011|
|Estimated Primary Completion Date:||May 2011 (Final data collection date for primary outcome measure)|
Arm A: Vitamin D 2,000 units daily all in one capsule for 6 months
Drug: Placebo in arm A and Vitamin D in arm B
Vitamin D3 at 2,000 units daily, all in one capsule, for 6 months and Placebo provided in matching capsule, one capsule daily, for 6 months
Other Name: Vitamin D3 is also called cholecalciferol
Placebo Comparator: B
Arm B: matching placebo one capsule daily for 6 months
Drug: vitamin D 3 for arm A ,and matching placebo for arm B
Arm A 2,000 units of Vitamin D3 in one capsule daily for 6 months. Arm B matching placebo capsule, one daily for 6 months
Other Name: Cholecalciferol
Rationale : Low vitamin D levels hinders the ability of the macrophage to produce activated 1-25Dihydroxyvitamin at sites of inflammation. 1-25Dihydroxyvitamin D has important immunoregulatory functions including down-regulation of antigen-presenting cells such as dendritic cells. Under the influence of 1-25Dihydroxyvitamin D, these dendritic cells become tolerogenic ─ as opposed to immunogenic ─ and abrogate an immune response at early stages. Immunogenic dendritic cells play a key role in the development of autoimmune diseases such as Rheumatoid Arthritis (RA) by "presenting" self-antigens to the immune system. Vitamin D levels are frequently low in patients with RA. Restoring vitamin D availability to normal levels in patients with RA may induce improvement of disease manifestations through expansion of the tolerogenic dendritic cell subset.
- Conduct a double-blind randomized clinical trial, to test the hypothesis that vitamin D administered to patients with active RA has beneficial effects on this disease.
- Determine if vitamin D administered to patients with RA. induces expansion of the tolerogenic dendritic cell subset by analyzing patterns of cell surface marker expression on dendritic cells at different time points during the clinical trial (translational studies).
Study Population: We will recruit early RA patients (not more that 12 month duration of disease)with active joint inflammation cared for at this institution.Participants must be subjects with active RA at the time of inclusion, who are 18 years of age or older and have no history of other autoimmune disorders or other disorders such as cancer or osteoporosis which are also linked to vitamin D deficiency. The eligible patients with active RA should be on treatment for RA with Methotrexate at the time of inclusion. Patients taking anti-cytokine treatments (considered not standard) would be excluded. Other exclusions include hypercalcemia, and a history of renal failure or renal stones.
20-25 participants will be allocated to the Vitamin D Group, Arm A. 20-25 participants will be allocated to Placebo Group Arm B Allocation will be conducted in a randomized, double-blind fashion.
Summary of Procedures : After signing a written consent, all potential candidates will undergo a screening interview with the PI and screening blood tests (a blood sample of 20 ml is required).
RA subjects who qualify to receive the study treatment will be randomized to receive oral vitamin D 2,000 units or placebo daily for 6 months. Patients will be examined on a monthly basis and will be drawn a 20 ml blood sample every 2 months for monitoring purposes for a period of 12 month. The participants within the clinical trial who also participate in the translational studies on dendritic cells, will be drawn an additional blood sample of 40 ml on the first month and at the end of the study to isolate their blood dendritic cells. We will study the expression of different activation markers on dendritic cells from consenting participants using various immunologic techniques. This will allow us to identify and quantify the tolerogenic dendritic cells..
Please refer to this study by its ClinicalTrials.gov identifier: NCT00279461
|United States, Indiana|
|Indianapolis, Indiana, United States, 46202|
|Principal Investigator:||Ernesto N Levy, MD||India na University|