Ambroxol Therapy for Patients With Type 1 Gaucher Disease and Suboptimal Response to Enzyme Replacement Therapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- bone mineral density evaluated by Dual Energy X-ray Absorptiometry (DEXA)
研究概览
简要总结
Ambroxol hydrochloride, an over-the-counter antitussive available in many markets , was identified as an interesting pharmacological chaperone. In addition to a mucolytic action, ambroxol has antioxidant and anti-inflammatory properties. Importantly, ambroxol therapy was found safe when given to pregnant women for prevention of neonatal respiratory distress syndrome .
Thus, ambroxol, an oral available drug on the market, may be a safe option for GD patients with potential disease-specific efficacy and should be expanded into a clinical trial using higher doses and placebo-controlled design. The investigators propose to start with a phase II study for patients with type 1 GD and suboptimal response to ERT. In addition the investigators plan to open an international registry of patients with GD currently receiving ambroxol (off study).
详细描述
Introduction:
Description of the Problem:
Enzyme replacement therapy (ERT) makes a significant impact on the clinical manifestations and quality of life of patients with Gaucher disease (GD) . The goals of therapy focus mainly on platelets, hemoglobin, spleen, liver, bones and growth parameters for children.
ERT is mostly effective in patients with type 1 GD; still some patients don't achieve normalization or near normalization of the therapeutic targets . Glucosylsphingosine (LysoGb1) is the most specific and sensitive, and hence is probably the best currently available GD biomarker. A level of LysoGB1 < 140 ng/ml is considered a marker for controlled GD (personal communication).
Patients with GD may also experience chronic fatigue that causes functional disability and adversely affects quality of life . The fatigue severity scale (FSS) is a 9-item tool; each item is scored on a scale from 1 to 7, with a mean score of 4 or higher considered to represent significant fatigue . Patients with GD have improvements in fatigue within 6 months of starting ERT, and that it may be among the first symptoms to show significant improvement. Using the FSS, no association was identified between fatigue and time on ERT (P = 0.57). In a survey of patients with Type 1 GD and physicians, patients ascribed greater importance to fatigue than other disease parameters, while physicians placed more emphasis on objective measures of visceral and hematologic disease manifestations.
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
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •*Adult patients ≥ 18 years with type 1 GD and suboptimal response to ERT defined as one or more than one of the following: platelet count < 100 x 103/mm3 bone mineral density < -2 T score Lyso-GB1 > 200 ng/ml.
- •*No change in dose or preparation of ERT in the last 12 months (Except for Naive patients)
排除标准
- •Patients with comorbidity that may impact on the primary and/or secondary endpoint.
- •Pregnant women will be excluded from the study.
- •Inability to cooperate with the study procedure
- •Hypersensitivity or any other contraindication listed in the local labeling of ambroxol
- •Refusal of patients to participate in the study.
研究组 & 干预措施
Ambroxol
Ambroxol therapy will be dosed up to 600 mg/day divided to twice a day starting 150 mg for the first month, 300 mg for the following month and 600 mg for the following month.
The study was conducted in accordance with the provisions of the Declaration of Helsinki, Good Clinical Practice guidelines, and local laws and regulations.
干预措施: Ambroxol (Drug)
结局指标
主要结局
bone mineral density evaluated by Dual Energy X-ray Absorptiometry (DEXA)
时间窗: 12 months.
Bone Mineral Densitometry (BMD)
Platelets count
时间窗: 12 months.
Increase in platelet count
Lyso-GB1 biomarker for Gaucher disease
时间窗: 12 months
decrease in Lyso-GB1.
次要结局
- Patient-reported outcomes (PRO)(12 months)
- Fatigue Severity Scale (FSS)(12 months)