Inherited Thrombocytopenias: Discovering the "New" Forms That Affect Half of Patients and Developing an in Vitro Tool for Testing the Ability of New Drugs to Increase Platelet Production and Predicting the Response to Treatment in the Individual Patient
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 159
- 试验地点
- 1
- 主要终点
- Identification and assessment of the causative role of candidate genes for new ITs
研究概览
简要总结
Inherited thrombocytopenias (ITs) are rare conditions characterized by low platelet count resulting in impaired hemostasis.
Recent advances revealed that several forms expose patients to the risk of developing additional and life-threatening disorders. Making a definite diagnosis is essential to identify patients' prognosis, personalize follow-up and treatment. Furthermore, Eltrombopag, an oral drug mimicking thrombopoietin (THPO), was able to increase the number of platelets in most of the few patients treated so far. Despite these advances, knowledge on ITs is still unsatisfactory, in that nearly half of patients have yet unknown forms. Moreover, the individual patient's response to Eltrombopag can't be predicted. This project wants to improve knowledge on ITs by two approaches: identification and characterization of new ITs; an in vitro bone marrow model not only for pre-clinical pharmacological studies of innovative drugs, but also for predicting individual response to treatment.
详细描述
The major problems when dealing with Inherited thrombocytopenias (ITs) are:
- achieving a diagnosis of certainty;
- setting up a personalized and effective treatment.
a) Near 50% of subjects remain without a diagnosis because they don't fit the diagnostic criteria for any known IT and don't have mutations in the causative genes identified so far. Our project, aimed at identifying new ITs by whole exome sequencing(WES) of a large number of subjects with unknow forms, will fill this gap; b)We want to improve therapy for ITs, which is presently mainly based on platelet transfusion, by the identification of new drugs and the usage of an innovative tool to predict in vitro patients' response to different treatment, allowing us to personalize therapeutic approaches.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Exclusion of any known IT after the application of a validated diagnostic algorithm based on clinical and laboratory criteria;
- •Absence of mutations in genes known to be causative for IT;
- •Acquisition of written informed consent.
排除标准
- 未提供
结局指标
主要结局
Identification and assessment of the causative role of candidate genes for new ITs
时间窗: 3 years
次要结局
未报告次要终点
研究者
Federica Melazzini
MD
Fondazione IRCCS Policlinico San Matteo di Pavia