Sodium Thiosulfate Treatment of Vascular Calcification in ESRD
キーワード
概要
説明
Hypothesis 1: The treatment of HD patients with high CAC scores with sodium thiosulfate for 5 months will decrease the amount of calcium in their coronary arteries.
Patients who are at high risk for having coronary calcification (history of MI, ischemic heart disease, peripheral or carotid artery disease) will be selected to undergo testing. We will recruit 60 HD patients receiving treatment in our units to undergo MDCT scanning along with non-invasive testing of PWV and CIMT. Assuming that 60% will have a CAC score of ≥50, 36 patients will be treated with sodium thiosulfate. We will administer 25% sodium thiosulfate solution (American Reagent Laboratories, Shirley, NY) at a dose of 12.5-25g/1.73m2 per over 15-30 minutes after each hemodialysis session for a total of 60 treatments (5 months). Assuming a 35% attrition rate, 23 patients will complete the entire protocol and undergo a repeat study of the initial battery of tests.
Rationale for treatment with sodium thiosulfate: Sodium thiosulfate, used as an antidote for cyanide poisoning for more than a century, is also an anti-oxidant, and binds with calcium to form a highly soluble calcium thiosulfate salt. The solubility of calcium thiosulfate salt is 250-100,000 fold higher than calcium oxalate or calcium phosphate salt. It has been used to treat recurrent calcium kidney stones and tumoral calcinosis (ectopic calcification usually around joints). It has also been used successfully in treating calcific uremic arteriopathy, a disease of small artery and soft tissue calcification, in several studies of dialysis patients and in our own experience of 5 patients. By 2 months there is radiological evidence of reduction in soft tissue calcification. Unpublished data also have demonstrated regression of established aortic calcification in uremic rats.
Sodium thiosulfate is a FDA approved medication for the treatment of cyanide poisoning. It is classified by the FDA as "generally recognized as safe". There are no known contraindications. The only side effects reported during intravenous (IV) administration in ESRD patients are nausea, vomiting and hyperosmia during the administration, which can be alleviated by pre-administration of anti-emetic medications. Sodium thiosulfate is slowly given through the dialysis venous line toward the end of HD treatments. The selected dose for this pilot study is the same as that used for the treatment of calcific uremic arteriopathy.
We will freeze 10 ml of serum obtained prior to and then monthly during treatment for subsequent analyses. Included in the analysis will be Fetuin-A levels but other relevant markers will be considered. Blood will also be frozen for future genomic studies.
日付
最終確認済み: | 10/31/2012 |
最初に提出された: | 12/04/2007 |
提出された推定登録数: | 12/04/2007 |
最初の投稿: | 12/05/2007 |
最終更新が送信されました: | 11/07/2012 |
最終更新日: | 11/19/2012 |
最初に提出された結果の日付: | 09/25/2011 |
最初に提出されたQC結果の日付: | 10/04/2012 |
最初に投稿された結果の日付: | 11/05/2012 |
実際の研究開始日: | 11/30/2007 |
一次完了予定日: | 10/31/2009 |
研究完了予定日: | 10/31/2009 |
状態または病気
介入/治療
Drug: Active Treatment
段階
アームグループ
腕 | 介入/治療 |
---|---|
Experimental: Active Treatment This is the only arm and involves active treatment with sodium thiosulfate in those subjects with high coronary artery calcium scores. | Drug: Active Treatment sodium thiosulfate 12.5-25 gm/M2 after each thrice weekly hemodialysis treatments for 5 months. |
適格基準
研究の対象となる年齢 | 18 Years に 18 Years |
研究に適格な性別 | All |
健康なボランティアを受け入れる | はい |
基準 | Inclusion Criteria: - Hemodialysis patient with thrice weekly treatments - Coronary artery calcium score greater than 50 - Age greater than 18 - Compliant with hemodialysis treatments - Informed consent Exclusion Criteria: - Allergy to sodium thiosulfate - Pregnancy - Incarceration - Enrollment in another study - Life expectancy less than 5 months - Expectation of recovery of renal function - Urine output of greater than 200 ml/day or contrast allergy will not receive intravenous contrast |
結果
主な結果の測定
1. Change in Annualized Coronary Calcium Volume Score After Treatment With Sodium Thiosulfate. [5 months]