Vitamin D to Improve Endothelial Function in SLE

NCT01911169 | Completed Phase 2 Results DMC

• 1 other identifier: 00009197
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

Determine the effect of vitamin D repletion on flow mediated dilation (FMD, a measure of endothelial function) in vitamin D deficient systemic lupus erythematosus (SLE) patients. The investigators will enroll vitamin D deficient SLE patients and randomize them to receive either 400 IU or 5,000 IU of cholecalciferol (D3) daily and measure change in FMD as a measure of EC function at baseline and after 16 weeks of repletion. Determine mechanisms by which vitamin D repletion may improve endothelial function in vitamin D deficient SLE patients and in vitro. Determine effect of oral D3 repletion on the Type I interferon signature in WISH and ECs cultured with pre and post plasma from D3 treated lupus patients. Determine effect of D3 repletion on the number of circulating apoptotic and non-apoptotic EC and EPC ex vivo. Determine effect of exogenous 1,25(OH)D on IFN gene signature in WISH and ECs stimulated by pretreatment SLE plasma in vitro. Determine the effects of exogenous 1,25(OH)D on the phenotype of ECs cultured with pretreatment lupus plasma. This study is designed to efficiently test our hypothesis and begin to define interferon-dependent pathways through which vitamin D repletion can restore clinical and in vitro endothelial function.

Conditions

Atherosclerosis; Systemic Lupus Erythematosus

Keywords

atherosclerosis; systemic lupus erythematosus; flow mediated dilation; interferon gene signature

Outcome Measures

Primary Outcomes (1)

• Change at Week 16 in % Flow Mediated Dilation in Those Who Did and Did Not Replete Vitamin D

  Measures were be performed with a Phillips iU22 Ultrasound system and a L9-3 9 mHz probe in 2D mode by a single operator using EKG gating. Baseline measures of brachial artery diameter will be made after the 10 minutes of rest. The blood pressure cuff, placed on the ipsilateral forearm, was inflated to 50 mmHg above the patient's systolic blood pressure for five minutes and then released. Endothelium-dependent FMD was measured continuously during and for three minutes after cuff release. Subjects rested for 10 minutes. Then, endothelium-independent dilation was measured 3 minutes after administration of 0.4 mg of sublingual nitroglycerine. The outcome (%FMD) was the difference between the average endothelium dependent diameter after cuff deflation and the average baseline diameter. The absolute difference between the % FMD at baseline and 16 week follow up was reported.

  from zero to sixteen weeks

Secondary Outcomes (1)

• Change in Interferon Signature

  from zero to sixteen weeks

Study Arms (2)

Vitamin D 5000

EXPERIMENTAL

5,000 IU vitamin D (cholecalciferol) given orally daily

Drug: Cholecalciferol

Vitamin D 400

ACTIVE COMPARATOR

cholecalciferol 400 IU daily by mouth

Drug: Cholecalciferol

Interventions

Cholecalciferol DRUG

5,000 International units versus 400 international units as an active comparator

Also known as: vitamin D3, Wegman's made by International Vitamin Corporation

Vitamin D 400; Vitamin D 5000

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of SLE per 1997 American College of Rheumatology Criteria(at least 4 criteria present)
• Documented Vitamin D deficiency
• Able to give informed consent

You may not qualify if:

• Using tobacco products
• Pregnant/Planning pregnancy
• Known Hypercalcemia (Serum Ca \>10.4)
• Known Hypercalcuria (Calcium/Creatinine \>0.8)
• Chronic active lupus nephritis or end stage renal disease or kidney stones
• Known Hyperparathyroidism
• Known chronic viral/mycobacterial infections
• Uncontrolled medical disease - Pl judgment
• Current drug or alcohol abuse
• Anticipated poor compliance/known neuropsychiatric disorders
• Hx of cardiovascular events (i.e. Ml, PVD, CVE)
• Subjects taking medications known to affect FMD in lupus subjects such as but not limited to fish oil, statins, will remain on stable doses throughout the study.

Sponsors & Collaborators

• Medical University of South Carolina: lead

Study Sites (1)

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Related Links

• SCResearch.org is the South Carolina Research Studies Directory designed specifically to help people locate research studies in which to participate.

MeSH Terms

Conditions

Atherosclerosis; Lupus Erythematosus, Systemic

Interventions

Cholecalciferol

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. James Oates
• Organization: Medical University of South Carolina

oatesjc@musc.edu

843-789-6797

Study Officials

• James Oates, MD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: July 22, 2013
• First Posted: July 30, 2013
• Study Start: June 1, 2011
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: October 27, 2017
• Results First Posted: October 27, 2017

Record last verified: 2017-09

Data Sharing

• IPD Sharing: Will share

Locations

US (1)