Vitamin D to Improve Endothelial Function in SLE
Vitamin D Repletion to Improve Endothelial Function in Lupus Patients
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.
調査の概要
詳細な説明
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.
研究の種類
入学 (実際)
段階
- フェーズ2
連絡先と場所
研究場所
-
-
South Carolina
-
Charleston、South Carolina、アメリカ、29425
- Medical University of South Carolina
-
-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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.
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:防止
- 割り当て:ランダム化
- 介入モデル:単一グループの割り当て
- マスキング:4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
---|---|
実験的:Vitamin D 5000
5,000 IU vitamin D (cholecalciferol) given orally daily
|
5,000 International units versus 400 international units as an active comparator
他の名前:
|
アクティブコンパレータ:Vitamin D 400
cholecalciferol 400 IU daily by mouth
|
5,000 International units versus 400 international units as an active comparator
他の名前:
|
この研究は何を測定していますか?
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
Change at Week 16 in % Flow Mediated Dilation in Those Who Did and Did Not Replete Vitamin D
時間枠:from zero to sixteen weeks
|
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
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
Change in Interferon Signature
時間枠:from zero to sixteen weeks
|
This outcome was not measured as planned
|
from zero to sixteen weeks
|
協力者と研究者
捜査官
- 主任研究者:James Oates, MD、Medical University of South Carolina
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- 00009197
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
Published - 1. Kamen DL, Oates JC.A Pilot Study to Determine if Vitamin D Repletion Improves Endothelial Function in Lupus Patients. Am J Med Sci 2015;350:302-7.
data available upon request
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。