Clinical trial NCT00710021: Vitamin D3 in Systemic Lupus Erythematosus
Official title: Effect of Vitamin D3 on the IFN Alpha Signature in Patients With Systemic Lupus Erythematosus (ALE02)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Systemic Lupus Erythematosus
SLE
Lupus
Keywords: Systemic lupus erythematosus
SLE
Vitamin D3
Vitamin D deficiency
IFN alpha expression
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Autoimmunity Centers of Excellence
First posted: 2008-07-03
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to explore the impact of vitamin D3 on the expression of alpha interferon (IFN alpha) expression in systemic lupus erythematosus (SLE) patients with vitamin D deficiency.

Detailed description: Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies with subsequent immune complex deposition and tissue inflammation. The role of interferon (IFN) alpha in the development of SLE has been repeatedly documented. Vitamin D deficiency is common among lupus patients. Vitamin D is recognized as a regulator of immune response. This study will explore the impact of vitamin D3 supplementation on IFN alpha expression in SLE patients.

The study will last approximately 12 weeks and consist of three treatment groups: 1.) Participants will receive vitamin D3 2000 IU daily 2.) Participants will receive vitamin D3 4000 IU daily 3.) Participants will receive a vitamin D3 placebo daily. There will be four study visits for each participant. Visits will occur at screening, study entry, and Weeks 6 and 12. Physical examination, vital signs, and blood and urine tests will occur at all visits. For females of childbearing potential, a pregnancy test will be performed at screening and Week 6.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of SLE by American College of Rheumatology (ACR) criteria
* Serum 25-OH vitamin D level of 20 ng/mL or less
* Stable disease at screening, defined as a modified Safety of Estrogens in Lupus Erythematosus National Assessment SLE Disease Activity Index (SELENA-SLEDAI) of 4 or less
* Interferon (IFN) signature present. More information about this criterion can be found in the protocol
* Positive anti-double-stranded (anti-ds) DNA antibody blood test at screening
* If on corticosteroids, the dose must be less than 20 mg per day and stable for 4 weeks prior to screening and at study entry
* If on immunosuppressive or immunomodulatory medication such as azathioprine, methotrexate, leflunomide, mycophenolate, or hydroxychloroquine, the dose must be stable for 3 months prior to screening and at study entry
* If receiving a multivitamin or a vitamin D supplement, the dose of vitamin D must be 800 IU daily or less and stable for the 3 months prior to screening and at study entry
* Agree to use effective contraceptive methods for the duration of the study

Exclusion Criteria:

* Unwilling to stop using drugs or substances that may interfere with fat absorption
* Hypercalcemia
* Hypercalciuria
* History of hyperparathyroidism
* History of kidney stones
* History of cancer, except cervical carcinoma in situ and resected basal and squamous cell carcinomas of the skin
* Known history of chronic viral infections, including human immunodeficiency virus (HIV), Hepatitis B, and Hepatitis C
* Known active tuberculosis
* Any British Isles Lupus Assessment Group (BILAG) A or B manifestation with the exception of a BILAG B mucocutaneous manifestation
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) liver function tests greater than or equal to two times the upper limit of normal
* Dialysis or serum creatinine greater than 1.5 mg/dL
* Expectation by the investigator to increase corticosteroid or immunosuppressive or immunomodulatory medication dose at screening, study entry, or over the course of the study
* Treatment with cyclophosphamide within 3 months of screening
* Treatment with rituximab within 12 months of screening
* Other investigational drug and or treatment during the 4 weeks or seven half lives of the other investigational drug prior to study entry
* Drug or alcohol abuse within 6 months prior to study entry
* Treatment with digoxin
* Treatment with teriparatide
* Any condition that, in the opinion of the investigator, would jeopardize the subject's safety following exposure to the study drug
* Pregnant or breastfeeding

Primary outcomes:
measure: Percent of Participants With an IFN Alpha Signature Response at Week 12
timeFrame: 0, Week 12
Secondary outcomes:
measure: Percent of Participants With an IFN Alpha Signature Response at Week 6
timeFrame: 0, Week 6
measure: Percent of Participants With IFN Alpha Signature at Week 12
timeFrame: 0, Week 12
measure: Percent of Participants With IFN Alpha Signature at Week 6
timeFrame: Week 6
measure: qRT-PCR Fold Change in Ifit1 Gene Expression From Baseline to Week 12
timeFrame: 0, Week 12
measure: qRT-PCR Fold Change in Ifit1 Gene Expression From Baseline to Week 6
timeFrame: 0, Week 6
measure: qRT-PCR Fold Change in Ifi44 Gene Expression From Baseline to Week 12
timeFrame: 0, Week 12
measure: qRT-PCR Fold Change in Ifi44 Gene Expression From Baseline to Week 6
timeFrame: 0, Week 6
measure: qRT-PCR Fold Change in Mx1 Gene Expression From Baseline to Week 12
timeFrame: 0, Week 12
measure: qRT-PCR Fold Change in Mx1 Gene Expression From Baseline to Week 6
timeFrame: 0, Week 6
measure: Change in Serum C3 Level From Baseline to Week 12
timeFrame: 0, Week 12
measure: Change in Serum C3 Level From Baseline to Week 6
timeFrame: 0, Week 6
measure: Change in Serum C4 Level From Baseline to Week 12
timeFrame: 0, Week 12
measure: Change in Serum C4 Level From Baseline to Week 6
timeFrame: 0, Week 6
measure: Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 12
timeFrame: 0, Week 12
measure: Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 6
timeFrame: 0, Week 6
measure: Change in SELENA-SLEDAI Total Score From Baseline to Week 12
timeFrame: 0, Week 12
measure: Cardiorespiratory BILAG Status at Week 12
timeFrame: Week 12
measure: Constitutional BILAG Status at Week 12
timeFrame: Week 12
measure: Gastrointestinal BILAG Status at Week 12
timeFrame: Week 12
measure: Hematological BILAG Status at Week 12
timeFrame: Week 12
measure: Mucocutaneous BILAG Status at Week 12
timeFrame: Week 12
measure: Musculoskeletal BILAG Status at Week 12
timeFrame: Week 12
measure: Neuropsychiatric BILAG Status at Week 12
timeFrame: Week 12
measure: Ophthalmic BILAG Status at Week 12
timeFrame: Week 12
measure: Renal BILAG Status at Week 12
timeFrame: Week 12
measure: Percent of Participants With Adverse Events of Grade 3 or Above
timeFrame: From start of study treatment through Week 12
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Manhassett
country: United States
facility: Feinstein Institute for Medical Research
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
Study officials:
affiliation: Northwell Health
name: Cynthia Aranow, MD
role: STUDY_CHAIR
affiliation: Medical University of South Carolina
name: Diane Kamen, MD
role: STUDY_CHAIR
References:
citation: Kamen DL, Cooper GS, Bouali H, Shaftman SR, Hollis BW, Gilkeson GS. Vitamin D deficiency in systemic lupus erythematosus. Autoimmun Rev. 2006 Feb;5(2):114-7. doi: 10.1016/j.autrev.2005.05.009. Epub 2005 Jun 21.
citation: Mangini AJ, Lafyatis R, Van Seventer JM. Type I interferons inhibition of inflammatory T helper cell responses in systemic lupus erythematosus. Ann N Y Acad Sci. 2007 Jun;1108:11-23. doi: 10.1196/annals.1422.002.
citation: Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Talal N, Winchester RJ. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982 Nov;25(11):1271-7. doi: 10.1002/art.1780251101.
citation: Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997 Sep;40(9):1725. doi: 10.1002/art.1780400928. No abstract available.
citation: Isenberg DA, Rahman A, Allen E, Farewell V, Akil M, Bruce IN, D'Cruz D, Griffiths B, Khamashta M, Maddison P, McHugh N, Snaith M, Teh LS, Yee CS, Zoma A, Gordon C. BILAG 2004. Development and initial validation of an updated version of the British Isles Lupus Assessment Group's disease activity index for patients with systemic lupus erythematosus. Rheumatology (Oxford). 2005 Jul;44(7):902-6. doi: 10.1093/rheumatology/keh624. Epub 2005 Apr 6.
citation: Aranow C, Kamen DL, Dall'Era M, Massarotti EM, Mackay MC, Koumpouras F, Coca A, Chatham WW, Clowse ME, Criscione-Schreiber LG, Callahan S, Goldmuntz EA, Keyes-Elstein L, Oswald M, Gregersen PK, Diamond B. Randomized, Double-Blind, Placebo-Controlled Trial of the Effect of Vitamin D3 on the Interferon Signature in Patients With Systemic Lupus Erythematosus. Arthritis Rheumatol. 2015 Jul;67(7):1848-57. doi: 10.1002/art.39108.