Haemophilia and Bone Loss PHILEOS Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 448
- 试验地点
- 46
- 主要终点
- Osteoporosis defined by a T-score < -2.5 in severe haemophilic patients without prophylaxis and in healthy subjects.
研究概览
简要总结
Haemophilia is a rare bleeding disorder, characterized by factor VIII (HA) or factor IX (HB) deficiency. The absence or the reduction of fVIII or fIX result in impaired thrombin generation and clot formation, causing excessive bleeding (mainly haemarthrosis). Osteoporosis is a systemic bone disease characterized by a low bone mineral density (BMD). A decrease of mean BMD has been described in haemophilic patients compared to healthy controls in several studies. So, osteoporosis could be an underestimated haemophilia-related comorbidity. None of the following risk factors (reduced physical activity, joint damage, vitamin D deficiency and /or hepatitis C virus (HCV) infection) has been retained as a cause of osteoporosis in haemophilic patients. Another hypothesis is that bone loss could be directly linked to fVIII or fIX and/or thrombin deficiency. The aim of this study is to evaluate the prevalence of the bone loss in HA and B patients, according to the type, the severity and the presence (or not) of a prophylactic treatment (depending on the age at which it was began) and to compare it to a control population. The investigators will also evaluate the relation between BMD and FVIII, fIX and thrombin potential.
详细描述
Recruitment of healthy volunteers through registers (Clinical Investigation Centers) and advertisements.
Recruitment of haemophilic patients during a routine visit at the haemophilia centre.
Information of the subjects that the study requires a BMD measure for all and a blood sampling for patients only.
After inclusion and exclusion criteria have been checked, the subject can sign the consent.
For all subjects, an appointment will be made for BMD measure. For patients and controls: BMD will be measured by Dual Energy X-ray Absorptiometry (DXA) technology, on femoral and lumbar spine (L2-L4) sites.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Screening
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 60 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy Volunteers :
- •Healthy men aged between 20 to 60 years old
- •Haemophilic Patients:
- •Haemophilia A and B patients, irrespective of the disease form (mild, moderate, severe with or without prophylaxis)
- •Haemophilic patients aged between 20 to 60 years old
- •Severe Haemophilia A patients with prophylaxis : last factor VIII injection more than 48 to 120 hours (depending on on the prophylactic treatment) prior blood sampling dedicated to the this research
- •Severe Haemophilia B patients : last factor IX injection more than 5 to 21 days (depending on the prophylactic treatment) prior blood sampling dedicated to the this research
排除标准
- •Healthy Volunteers:
- •History of disease known to influence bone metabolism (hyperthyroidism, hyperparathyroidism, hypercorticism, hypogonadism, diseases that require long-term use of corticoids, …)
- •Past or present treatment with any osteoporotic medication other than Vit D or Ca++
- •Presence of two total hip prostheses
- •HIV documented infection
- •HCV documented infection (in progress or cured) at cirrhotic stage
- •Haemophilic Patients:
- •Haemophilic patients with current or history of inhibitor anti-fVIII or anti-fIX (>5 Bethesda Units)
- •Treatment with HEMLIBRA (Emicizumab). Unless it is possible to use a result of thrombin generation prior to this treatment and achieved with a residual rate not greater than or equal to 5%.
- •History of disease known to influence bone metabolism and not related to haemophilia (hyperthyroidism, hyperparathyroidism, hypercorticism, hypogonadism, diseases that require long-term use of corticoids, …)
- •Past or present treatment with any anti-osteoporotic medication other than Vit D or Ca++
- •Presence of two total hip prostheses
- •HIV documented infection
- •HCV documented infection (in progress or cured) at cirrhotic stage
研究组 & 干预措施
Haemophilic patients
Blood sampling Bone Densitometry (BMD)
干预措施: Bone densitometry (BMD) (Radiation)
Haemophilic patients
Blood sampling Bone Densitometry (BMD)
干预措施: Blood sampling for patients only (Biological)
Healthy volunteers
Bone Densitometry (BMD)
干预措施: Bone densitometry (BMD) (Radiation)
结局指标
主要结局
Osteoporosis defined by a T-score < -2.5 in severe haemophilic patients without prophylaxis and in healthy subjects.
时间窗: During the procedure
Bone mineral densitometry
次要结局
- Osteopenia defined by a T-score < -1 in the different groups of haemophilic patients and in in healthy subjects.(During the procedure)
- Bone mineral density (expressed as a T-score) in the different groups of haemophilic patients and in healthy subjects.(During the procedure)
- Markers influencing bone metabolism in all haemophilic patients included(At the inclusion)
- Osteoporosis defined by a T-score < -2.5 in the different groups of haemophilic patients and in in healthy subjects.(During the procedure)
- Basal level of fVIII/fIX (expressed as an Ag level or as a %) or thrombin generation potential (expressed as an endogenous thrombin potential (ETP), nmol/min) and Bone mineral density (expressed as a T-score and Z-score)(At the inclusion)