TREATMENT OF FAMILIAL HYPERCHOLESTEROLEMIA BY DEXTRAN SULFATE APHERESIS

硫酸葡聚糖血浆分离术治疗家族性高胆固醇血症

• 批准号: 5201143
• 负责人: S F LEITMAN
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5201143
• 关键词: adsorption; apolipoproteins; blood treatment; dextrans; heterozygote; high density lipoproteins; homozygote; human subject; human therapy evaluation; hypercholesterolemia; low density lipoprotein; serum albumin; sulfates

Patients with familial hypercholesterolemia (FH) are at high risk of premature coronary artery disease due to elevated low density lipoprotein (LDL) and Lp (a) cholesterol levels. Diet and drug therapy can reduce cholesterol concentrations in most patients with heterozygous FH, but a small proportion of heterozygous and nearly all homozygotes do not respond to therapy. Selective removal of LDL by dextran sulfate affinity adsorption was evaluated in these patients in a collaborative multicenter U.S. Study. The dextran sulfate apheresis system (Liposorber LA-15 Kanegatuchi, Japan) removed LDL and Lp(a) without affecting HDL or albumin concentrations, thus allowing return of autologous plasma and avoiding the need for colloid replacement solutions. Three homozygous and three heterozygous FH patients were enrolled at the Clinical Center; the total cohort enrolled nationwide included 10 homozygotes and 54 heterozygotes. The study is now complete and closed to further accrual of patients, although those having achieved documented benefit are permitted to continue LDL-apheresis treatments on an exemption basis granted by the FDA, pending device licensure. Treatments were administered in 7 to 14 day intervals. Mean acute reductions in total, LDL, and Lp (a) cholesterol levels were 70%, 81% and 68% respectively in homozygotes and 61%, 76% and 65% respectively in heterozygotes. Time-averaged levels of LDL cholesterol were reduced 53% *(447 to 310 mg/dl) in homozygous FH patients and 41% (243 to 143 mg/dl) in heterozygous ones. The treatments we well tolerated and no significant adverse reactions occurred. Our data suggest that dextran sulfate adsorption is a safe and effective way to clear plasma of LDL cholesterol, and has advantages, compared to simple plasma exchange, of eliminating the need for colloid replacement solutions and promoting a more beneficial LDL/HDL cholesterol ratio. The IDE number for the investigational device used in this study is G880069; the IDE holder is Kaneka America.

家族性高胆固醇血症 (FH) 患者罹患以下疾病的风险很高 低密度脂蛋白升高导致的过早冠状动脉疾病 (LDL) 和 Lp (a) 胆固醇水平。饮食和药物治疗可以减少 大多数杂合子 FH 患者的胆固醇浓度，但 小部分杂合子和几乎所有纯合子没有反应 来治疗。通过硫酸葡聚糖亲和力选择性去除 LDL 在多中心协作中对这些患者的吸附进行了评估 美国研究。硫酸葡聚糖单采系统（Liposorber LA-15 Kanegatuchi，日本）去除了 LDL 和 Lp(a)，而不影响 HDL 或白蛋白 浓度，从而允许返回自体血浆并避免 需要胶体替代解决方案。三个纯合子和三个 临床中心招募了杂合子 FH 患者；总计 全国范围内招募的队列包括 10 名纯合子和 54 名杂合子。 该研究现已完成并关闭以进一步招募患者， 尽管那些已经获得记录在案的利益的人被允许 在获得卫生部批准的豁免基础上继续进行低密度脂蛋白单采治疗 FDA，正在等待设备许可。治疗在 7 至 14 天内进行 间隔。总胆固醇、LDL 和 Lp (a) 胆固醇平均急剧下降 纯合子中的水平分别为 70%、81% 和 68%，纯合子中的水平分别为 61%、76% 和 杂合子中分别为 65%。 LDL 胆固醇的时间平均水平 纯合子 FH 患者中减少 53% *（447 至 310 mg/dl），而纯合子 FH 患者则减少 41% (243 至 143 mg/dl) 杂合子。我们耐受性良好的治疗 且未发生明显不良反应。我们的数据表明 硫酸葡聚糖吸附是清除血浆中安全有效的方法 LDL胆固醇，与简单的血浆置换相比具有优势， 消除对胶体替代解决方案的需求并促进 更有益的低密度脂蛋白/高密度脂蛋白胆固醇比率。 IDE 编号 本研究中使用的研究设备是 G880069； IDE 支架是 卡内卡美国.