Vitamin D to Improve Endothelial Function in SLE

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by Medical University of South Carolina
Sponsor:
Information provided by (Responsible Party):
Jim C. Oates, Medical University of South Carolina
ClinicalTrials.gov Identifier:
NCT01911169
First received: July 22, 2013
Last updated: July 26, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Atherosclerosis
Systemic Lupus Erythematosus
Drug: Cholecalciferol
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Vitamin D Repletion to Improve Endothelial Function in Lupus Patients

Resource links provided by NLM:


Further study details as provided by Medical University of South Carolina:

Primary Outcome Measures:
  • change in flow mediated dilation [ Time Frame: from zero to sixteen weeks ] [ Designated as safety issue: No ]
    Measures will 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, will be inflated to 50 mmHg above the patient's systolic blood pressure for five minutes and then released. Endothelium-dependent FMD will be measured continuously during and for three minutes after cuff release. Subjects will rest for 10 minutes. Then, endothelium-independent dilation will be measured 3 minutes after administration of 0.4 mg of sublingual nitroglycerine.


Secondary Outcome Measures:
  • change in interferon signature [ Time Frame: from zero to sixteen weeks ] [ Designated as safety issue: No ]
    endothelial cells will be incubated with patient serum and assayed for interferon gene expression


Estimated Enrollment: 32
Study Start Date: June 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vitamin D 5000
5,000 IU vitamin D (cholecalciferol) given orally daily
Drug: Cholecalciferol
5,000 International units versus 400 international units as an active comparator
Other Names:
  • vitamin D3
  • Wegman's made by International Vitamin Corporation
Active Comparator: Vitamin D 400
cholecalciferol 400 IU daily by mouth
Drug: Cholecalciferol
5,000 International units versus 400 international units as an active comparator
Other Names:
  • vitamin D3
  • Wegman's made by International Vitamin Corporation

Detailed Description:

Specific Aim 1. Determine the effect of vitamin D repletion on changes in flow mediated dilation (FMD) in vitamin D deficient SLE patients. The investigators hypothesize that 25(OH)D repletion will improve endothelial function in 25(OH)D deficient lupus patients. For this pilot study, the investigators have opted to use a Randomized Phase II screening design (36). The screening design is meant to provide preliminary comparisons of an experimental treatment to an appropriate control, with the idea that the pilot study would provide valuable information to aid in the design of a definitive Phase III evaluation, should the experimental treatment prove promising in the Phase II trial. The trial is designed to determine the effect of vitamin D repletion with D3 on FMD in vitamin D deficient SLE subjects. Approximately 50 SLE subjects will be screened for total 25(OH) vitamin D (25(OH)D) levels and inclusion/exclusion criteria. However, screening will continue only until 32 participants have been enrolled that have total serum 25(OH)vitamin D levels ≤ 20 ng/ml and meet inclusion/exclusion criteria. A baseline FMD, interferon (IFN) signature assays, and levels of circulating non- and apoptotic endothelial cells (EC) and endothelial progenitor cell (EPC) will be performed at the baseline visit. Participants will be will be randomized into two equal groups of 16 to receive one of two daily oral D3 doses previously used in supplementation trials with no evidence of harm. Group 1 (controls) will receive 400 international units (IU) of D3 daily. Group 2 will receive 5,000 IU daily. Studies of supplementation in subjects deficient in vitamin D demonstrate that supplementation with 1,000, 5,000, and 10,000 IU daily result in increases in 25(OH)D of 4.8, 36.7, and 63.8 ng/mL without evidence of toxicity (37). In this study, steady state levels were achieved at 90 days. As shown in our preliminary studies, 4,000 IU daily is safe and effective at repletion in our lupus clinic population. Some subjects had not achieved steady state at 90 days, so the invesitgators have chosen to dose for 16 weeks. The primary endpoint will be a change in FMD after 16 weeks of vitamin D repletion. The secondary endpoint will be the reduction in IFN signature and level of circulating apoptotic ECs/EPCs in response to vitamin D repletion from baseline to 16 weeks.

Specific Aim 2. Determine mechanisms by which vitamin D repletion may improve endothelial function in vitamin D deficient SLE patients and in vitro.

2.1 Determine effect of oral vitamin D3 repletion on the Type I interferon signature in WISH and ECs cultured with pre and post plasma from D3 treated lupus patients. The investigators hypothesize that the plasma-induced IFN gene signature will reduce with 25(OH)D repletion.

2.2 Determine effect of D3 repletion on the number of circulating apoptotic and non-apoptotic EC and EPC ex vivo. The investigators hypothesize that D3 repletion will reduce the number of apoptotic EC and EPC and increase the number of non-apoptotic EPC in association with improved FMD.

2.3 Determine effect of exogenous 1,25(OH)D on IFN gene signature in WISH and ECs stimulated by pretreatment SLE plasma in vitro. This aim is designed to address the specific question of whether the effect of vitamin D is at least partially due to a direct rather than indirect effect on endothelial response to SLE plasma IFN.

2.4 Determine the effects of exogenous 1,25(OH)D on the phenotype of ECs cultured with pretreatment lupus plasma. This aim was designed to probe the functional significance of vitamin D repletion and reduction of the IFN response on the endothelial phenotype.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01911169

Contacts
Contact: Abby Powell 843-792-0549 powab@musc.edu
Contact: Stephanie Slan, MBA 843-792-8997 slans@musc.edu

Locations
United States, South Carolina
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
Contact: Abby Powell, BS    843-792-0549    powab@musc.edu   
Contact: Stephanie Slan, MBA    843-792-8997    slans@musc.edu   
Principal Investigator: James Oates, MD         
Sub-Investigator: Diane Kamen, MD, MSCR         
Sub-Investigator: Gary Gilkeson, MD         
Sub-Investigator: Holly Mitchell, MD         
Sub-Investigator: Laura Parks, MD         
Sponsors and Collaborators
Medical University of South Carolina
Investigators
Principal Investigator: James Oates, MD Medical University of South Carolina
  More Information

Additional Information:
No publications provided

Responsible Party: Jim C. Oates, Associate Professor, Medical University of South Carolina
ClinicalTrials.gov Identifier: NCT01911169     History of Changes
Other Study ID Numbers: 00009197
Study First Received: July 22, 2013
Last Updated: July 26, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Medical University of South Carolina:
atherosclerosis
systemic lupus erythematosus
flow mediated dilation
interferon gene signature

Additional relevant MeSH terms:
Atherosclerosis
Lupus Erythematosus, Systemic
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Cholecalciferol
Vitamin D
Ergocalciferols
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on July 29, 2014