Vitamin D functions as a powerful immune modulator, deficiency of vitamin D is highly prevalent among SLE patients, and preclinical studies have shown success using vitamin D to treat animal models of autoimmune disease. We have preliminary data demonstrating that Caucasian SLE patients have significantly lower vitamin D levels compared to controls, and there is a strong trend towards higher disease activity in patients with lower levels of 25-hydroxyvitamin D (25(OH)D). Evidence from prospective studies of RA and type 1 diabetes in humans suggest an important role for vitamin D as a modifiable environmental factor in autoimmune disease. This role has not been well studied in human SLE. The overall hypothesis of this proposal is that vitamin D deficiency is a reversible environmental trigger of SLE and increased disease activity, and that supplementation with doses of vitamin D sufficient to achieve immune modulatory effects will be safe and attenuate disease activity in SLE patients. The Research Development Plan consists of 3 Aims.
In Specific Aim 1, 25(OH)D and iPTH will be performed on stored serum samples from participants from 3 longitudinal cohorts to determine whether vitamin D deficiency correlates with SLE compared to controls, and with disease activity and severity among cases.
In Specific Aim 2, we will determine the factors that protect the minority of African American SLE patients from becoming vitamin D deficient, assessing diet, sun exposure, supplement use, and skin pigment.
Specific Aim 3 involves administration of oral vitamin D to deficient African American SLE patients in a small Phase I clinical study to establish safety, tolerability, and an effective dose for replacement therapy. Disease activity, disease flare, immunologic measures, inflammatory markers, and quality of life will also be assessed. The information gathered from this study will be used to plan a scientifically sound larger scale Phase ll/lll placebo-controlled trial. The Career Development Plan will consist of 5 essential components: (1) Research projects preceptorship overseen by a research advisory and mentorship committee;(2) Meetings and conferences;(3) Training in the responsible conduct of research;(4) Formal mentorship training;and (5) Formal coursework to further develop a body of knowledge in relevant areas. These research and career development aims are designed to provide training in techniques for the cross-sectional analysis of large databases and for the design and implementation of clinical research studies in an outpatient setting. The pursuit of these projects, in conjunction with formal coursework in biostatistical and epidemiological methods, is intended to foster Dr. Kamen's career as an independent academic clinical investigator with a focus on SLE and patient-oriented research.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23AR052364-05
Application #
8100433
Study Section
Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee (AMS)
Program Officer
Wang, Yan Z
Project Start
2007-08-03
Project End
2012-09-30
Budget Start
2011-07-01
Budget End
2012-09-30
Support Year
5
Fiscal Year
2011
Total Cost
$129,465
Indirect Cost
Name
Medical University of South Carolina
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425
Williams, Edith M; Hyer, J Madison; Viswanathan, Ramakrishnan et al. (2017) Peer-to-peer mentoring for African American women with lupus: A feasibility pilot. Arthritis Care Res (Hoboken) :
Kamen, Diane L; Oates, Jim C (2015) A Pilot Study to Determine if Vitamin D Repletion Improves Endothelial Function in Lupus Patients. Am J Med Sci 350:302-7
Aranow, Cynthia; Kamen, Diane L; Dall'Era, Maria et al. (2015) Randomized, Double-Blind, Placebo-Controlled Trial of the Effect of Vitamin D3 on the Interferon Signature in Patients With Systemic Lupus Erythematosus. Arthritis Rheumatol 67:1848-57
Barnado, April; Wheless, Lee; Meyer, Anna K et al. (2014) Pregnancy outcomes among African-American patients with systemic lupus erythematosus compared with controls. Lupus Sci Med 1:e000020
Hoffecker, Brett M; Raffield, Laura M; Kamen, Diane L et al. (2013) Systemic lupus erythematosus and vitamin D deficiency are associated with shorter telomere length among African Americans: a case-control study. PLoS One 8:e63725
Monda, Keri L; Chen, Gary K; Taylor, Kira C et al. (2013) A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry. Nat Genet 45:690-6
Spruill, Ida J; Leite, Renata Serricchio; Fernandes, Jyotika K et al. (2013) Successes, Challenges and Lessons Learned: Community-engaged research with South Carolina's Gullah population. Gateways 6:
Ravenell, Roneka L; Kamen, Diane L; Spence, J David et al. (2012) Premature atherosclerosis is associated with hypovitaminosis D and angiotensin-converting enzyme inhibitor non-use in lupus patients. Am J Med Sci 344:268-73
Ritterhouse, Lauren L; Crowe, Sherry R; Niewold, Timothy B et al. (2011) B lymphocyte stimulator levels in systemic lupus erythematosus: higher circulating levels in African American patients and increased production after influenza vaccination in patients with low baseline levels. Arthritis Rheum 63:3931-41
Ritterhouse, Lauren L; Crowe, Sherry R; Niewold, Timothy B et al. (2011) Vitamin D deficiency is associated with an increased autoimmune response in healthy individuals and in patients with systemic lupus erythematosus. Ann Rheum Dis 70:1569-74

Showing the most recent 10 out of 16 publications