Vitamin D3 in Systemic Lupus Erythematosus

NCT00710021 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: DAIT ALE02
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 8

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.

Conditions

Systemic Lupus Erythematosus; SLE; Lupus

Keywords

Systemic lupus erythematosus; SLE; Vitamin D3; Vitamin D deficiency; IFN alpha expression

Outcome Measures

Primary Outcomes (1)

• Percent of Participants With an IFN Alpha Signature Response at Week 12

  Presence of an Interferon (IFN) Alpha signature response is defined as: a reduction in expression from baseline (Screening) of at least 50% for 1 of 3 IFN Alpha responsive genes (Ifit1, Ifi44, Mx1) with concurrent expression in the remaining 2 genes at a level not more than 25% above baseline, or a reduction in expression from baseline of at least 25% for 2 of the 3 IFN Alpha responsive genes with concurrent expression in the third gene at a level of no more than 25% above baseline. Gene expression was measured on peripheral blood samples using qRT-PCR. Missing data were considered as response failures during calculation.

  0, Week 12

Secondary Outcomes (26)

• Percent of Participants With an IFN Alpha Signature Response at Week 6

  0, Week 6

• Percent of Participants With IFN Alpha Signature at Week 12

  0, Week 12

• Percent of Participants With IFN Alpha Signature at Week 6

  Week 6

• qRT-PCR Fold Change in Ifit1 Gene Expression From Baseline to Week 12

  0, Week 12

• qRT-PCR Fold Change in Ifit1 Gene Expression From Baseline to Week 6

  0, Week 6

Study Arms (3)

vitamin D3 2000 IU

EXPERIMENTAL

Participants in this arm take a vitamin D3 dose of 2000 international units (IU) daily by mouth for a duration of 12 weeks.

Drug: Vitamin D3

vitamin D3 4000 IU

EXPERIMENTAL

Participants in this arm take a vitamin D3 dose of 4000 international units (IU) daily by mouth for a duration of 12 weeks.

Drug: Vitamin D3

vitamin D3 placebo

PLACEBO COMPARATOR

Participants in this arm take a vitamin D3 placebo daily by mouth for a duration of 12 weeks.

Drug: Vitamin D3 placebo

Interventions

Vitamin D3 DRUG

8% vitamin D3 powder, 84% microcrystalline cellulose, 8% fumed silica by weight

Also known as: Cholecalciferol

vitamin D3 2000 IU; vitamin D3 4000 IU

Vitamin D3 placebo DRUG

86% microcrystalline cellulose, 14% fumed silica by weight

Also known as: Cholecalciferol placebo

vitamin D3 placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Autoimmunity Centers of Excellence: collaborator

Study Sites (8)

University of Alabama

Birmingham, Alabama, 35294, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Feinstein Institute for Medical Research

Manhassett, New York, 11030, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15261, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Related Publications (6)

• 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.

  PMID: 16431339 BACKGROUND

• 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.

  PMID: 17893966 BACKGROUND

• 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.

  PMID: 7138600 BACKGROUND

• 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.

  PMID: 9324032 BACKGROUND

• 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.

  PMID: 15814577 BACKGROUND

• 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.

  PMID: 25777546 RESULT

Related Links

• National Institute of Allergy and Infectious Diseases (NIAID) website
• National Institute of Arthritis and Musculoskeletal and Skin Diseases: Handout on Health-System Lupus Erythematosus

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Vitamin D Deficiency

Interventions

Cholecalciferol

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Results Point of Contact

• Title: Director, Clinical Research Operations Program
• Organization: DAIT/NIAID

DAITClinicalTrialsGov@niaid.nih.gov

301-594-7669

Study Officials

• Cynthia Aranow, MD

  Northwell Health

  STUDY CHAIR

• Diane Kamen, MD

  Medical University of South Carolina

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2008
• First Posted: July 3, 2008
• Study Start: November 1, 2008
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: April 26, 2017
• Results First Posted: April 25, 2014

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will share

Locations

US (8)