A Phase II Multicenter Pilot Study of the Safety and Efficacy of Doxycycline/UrsoDeoxyCholicAcid on Disease Progression in ATTR Amyloidosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 55
- 试验地点
- 3
- 主要终点
- The efficacy on serum N terminal proBNP (NT-proBNP)
研究概览
简要总结
The primary objective for this study is to evaluate the efficacy of doxycycline + ursodeoxycholic acid (UDCA) on disease progression in Transthyretin Amyloidosis (ATTR) subjects with cardiomyopathy with or without neuropathy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Cardiomyopathy with septal thickness > 15 mm and/or S-NT-ProBNP > 300 ng/
- •Age >50 years
- •Male and females after menopause. Menopause is defined as 6 to 12 months of amenorrhea in a woman over 45 years of age.
- •Written informed consent to be obtained prior to any study procedure
- •Histochemical diagnosis of amyloidosis as based on detection by polarizing microscopy of green birefringent material in Congo red-stained tissue specimens, and typing of amyloid deposits as TTR and identification of amyloid fibril type.
- •Molecular definition of the TTR mutation or immunohistochemical staining of amyloid fibrils with anti TTR antibody
- •New York Heart Association (NYHA) class <III
- •Systolic blood pressure >100 mmHg (standing)
- •Must have symptomatic organ involvement with amyloid to justify therapy
排除标准
- •Liver transplantation in the previous 6 months or liver transplantation anticipated in less than 6 months;
- •ALT and/or AST > 2 x upper normal limit (UNL);
- •Creatinine clearance < 30 ml/min (Cockcroft -Gault Formula)
- •Any other lab values, illness or condition that in the opinion of the investigator might place the subject at unacceptable risk for participation in the study;
- •History of hypersensitivity to any of the ingredients of the study therapies;
- •Use of any investigational drug, device (or biologic) within 4 weeks prior to study entry or during the study.
研究组 & 干预措施
Doxycycline and UDCA
Doxycycline (200 mg/day intermittently) and UDCA (750 mg/day continuously)
干预措施: Doxycycline (Drug)
Doxycycline and UDCA
Doxycycline (200 mg/day intermittently) and UDCA (750 mg/day continuously)
干预措施: Ursodeoxycholic acid (Drug)
结局指标
主要结局
The efficacy on serum N terminal proBNP (NT-proBNP)
时间窗: At 12 month treatment
The primary endpoint of the study is the response rate to doxycycline + UDCA treatment at month 12. A responder is an ATTR subject with: - a reduction of, or an increase in serum NT-proBNP concentration of less than 30% of pre-treatment level will be regarded as consistent with treatment efficacy
次要结局
- Modified Body Mass Index (mBMI) reduction(12 month)
- Increase of septum thickness(12 month)
- Neurologic Kumamoto Scale(6, 12 and 18 month)
- Number of patients with adverse events(During 12 month treatment and during 6 month follow-up)
- Blood work for potential drug-related adverse events(18 months)
研究者
Ole B Suhr, Professor, MD, PhD
Professor, MD, PhD
Umeå University