Interest of Famotidine in Reducing Endothelial Expression of P-selectin in Children With Sickle Cell Disease: Pilot Study, Single-center, Prospective, Non-comparative.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Difference in plasma concentration of soluble P-selectin
研究概览
简要总结
The purpose of this study is to determine whether oral famotidine, a histamine type 2 receptor antagonist already widely used with very few side effects in other indications in children, is effective in reducing endothelial expression of P-selectin in children with sickle cell disease (SCD).
This pilot study will constitute the essential prerequisite for a randomized clinical trial comparing the efficacy of famotidine with that of placebo in the prevention of vaso-occlusive crises in SCD patients.
详细描述
Sickle cell disease (SCD) is a frequent and severe hemoglobinopathy, considered the first monogenic disease in the world. It is responsible for chronic hemolytic anemia, painful vaso-occlusive crises secondary to obstruction of the microcirculation by sickled red blood cells adhering to the vascular endothelium, and progressive organ damage secondary to ischemia/reperfusion phenomena.
Although the molecular bases are well known, the pathophysiology is still incompletely understood and therapeutic options remain limited. We have recently demonstrated an increase in plasma histamine levels (associated with mast cell activation) in SCD patients, particularly ≤ 18 years of age, at baseline and even more markedly during vaso-occlusive crises (Allali, Br J Haematol 2019). In vitro, an increase in the adhesion of red blood cells of SCD patients to human endothelial cells after stimulation with histamine has been described, via an increased expression of the adhesion molecule P-selectin. Abolition of this effect in the presence of famotidine, a histamine type 2 (H2) receptor antagonist, suggests that histamine is responsible for an increased adhesion mediated by P-selectin via stimulation of the H2 receptors. Therefore, our hypothesis is that long-term use of oral antihistamine therapy with famotidine may prevent vaso-occlusion by decreasing P-selectin expression by endothelial cells.
The main objective of the study is to assess the effect of famotidine on P-selectin expression after 29 days of oral treatment.
The secondary objectives are:
- to assess the effect of famotidine on the expression of other endothelial activation markers after 29 days of treatment;
- to assess the effect of famotidine on biomarkers of hemolysis and inflammation after 29 days of treatment;
- to assess the adverse effects of famotidine in a pediatric population suffering from sickle cell disease.
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
- 1 Year 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •child or adolescent aged 1 year to 17 years and 10 months, followed at the Necker-Enfants malades Hospital for a SS or Sβ0 SCD;
- •having at least one vaso-occlusive crisis in the year prior to inclusion;
- •for young girl of childbearing age (≥ 15 years old), a negative pregnancy test;
- •signed informed consent of the 2 parents or legal representative(s) and of the child of expressive age or the adolescent;
- •beneficiary of social security coverage or entitled (excluding AME)
排除标准
- •treatment with crizanlizumab (anti-P-selectin antibody);
- •treatment with atazanavir/ritonavir in combination with tenofovir;
- •known hypersensitivity to famotidine or to other histamine type 2 (H2) receptor antagonists;
- •cardiovascular history such as: arrhythmia, AVB (atrioventricular block), QT prolongation;
- •renal failure characterized by creatinine clearance <60 mL/min;
- •hepatic cytolysis (ALT ≥ 3N);
- •neutropenia (<1 G/L), thrombocytopenia (<80 G/L), reticulopenia (<80 G/L);
- •predictable poor adherence to treatment;
- •pregnancy or breastfeeding;
- •participation in another interventional research involving the human person;
- •planned bone marrow transplant or gene therapy within one month of inclusion.
- •Within 3 months prior to inclusion:
- •red blood cell transfusion;
- •introduction of hydroxyurea or modification of hydroxyurea doses;
- •introduction of L-glutamine or modification of L-glutamine doses;
- •introduction of voxelotor or modification of voxelotor doses;
- •taking oral or IV corticosteroids or any other immunomodulatory treatment;
- •taking an antihistamine treatment
- •In the month preceding inclusion:
- •occurrence of a vaso-occlusive crisis, acute chest syndrome or any vaso-occlusive phenomenon (acute splenic sequestration, priapism, stroke, occlusion of the central retinal artery, papillary necrosis);
- •occurrence of fever (≥ 38°C) or any infectious episode, febrile or not, suspected or confirmed, of a viral, bacterial, fungal or parasitic nature ;
- •occurrence of an acute hemolytic episode (increase in jaundice and pallor, decrease in hemoglobin level of ≥ 1 g/dL compared to baseline hemoglobin, increase in LDH and/or AST and/or free bilirubin deemed significant by the child's referring physician).
研究组 & 干预措施
Famotidine
Suspension of famotidine, 0.5 mg/kg/12h (with a maximum dose of 80 mg/day, regardless of the patient's weight) during 29 days.
干预措施: Famotidine 400 mg/50 mL (Drug)
结局指标
主要结局
Difference in plasma concentration of soluble P-selectin
时间窗: 29 days
Measurement by ELISA technique before and after 29 days of treatment
次要结局
- Difference in plasma concentration of soluble adhesion molecule: E-selectin(29 days)
- Difference in plasma concentration of soluble adhesion molecule: ICAM-1(29 days)
- Differences in blood values: hemoglobin, reticulocytes, AST, free bilirubin, LDH, and CRP(29 days)
- Occurrence of vaso-occlusive crisis(36 days)
- Difference in plasma concentration of soluble adhesion molecule: VCAM-1(29 days)
- Occurrence of serious or non-serious adverse event(s)(36 days)