Evaluation of a Long-term Endurance Training Program in Patients With Sickle Cell Disease: Benefits on Clinical Profile, Physical Fitness and Quality of Life of Patients
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 2
- 主要终点
- Number of vaso-occlusive crises (VOCs) with hospitalisation
研究概览
简要总结
Sickle cell disease (SCD), the most common genetic disease worldwide and in France, is an inherited haemoglobinopathy characterised by chronic haemolytic anaemia, vaso-occlusive crisis (VOC), acute pain, and multi-organ damage. Due to anaemia and multiple pulmonary, cardiac, endothelial, muscle, and metabolic dysfunctions, fatigue and poor physical capacity are common in SCD patients and constitute the primary reason for a sedentary lifestyle.
However, recent findings demonstrated in the first randomised, controlled, and prospective study implementing endurance training in SCD that, when adequately calibrated, regular moderate-intensity endurance training is not only safe but also beneficial for patients (primary outcome: improvement of physical ability).
This pivotal randomised, controlled, prospective study is designed to prove, on a large multicentre cohort, adult and paediatric, including patients with complications and over a longer period (one year).
The objective of the study is to demonstrate the efficacy of participating in a program of regular physical activity to reduce the rate of vaso-occlusive crises requiring hospitalisation and to improve physical ability in patients with SCD.
详细描述
Sickle cell disease (SCD) is an inherited haemoglobinopathy characterised by chronic haemolytic anaemia, vaso-occlusive crisis (VOC), acute pain, and multi-organ damage, making it the most common genetic disease in France. The mutation involves the substitution of glutamic acid by valine at position β6, leading to the synthesis of abnormal haemoglobin (HbS). The properties of HbS differ significantly from those of normal haemoglobin (HbA). Under deoxygenated conditions, HbS tends to polymerize, inducing deformation of the red blood cell (RBC), causing it to take on a sickle shape.
This leads to a very low haemoglobin concentration and haematocrit (typically 6-8 g/dL and 25%-30%, respectively). Anaemia, coupled with arterial desaturation, results in tissue hypoxia. Furthermore, RBCs containing HbS (RBC-HbS) are less deformable and exhibit abnormal adherence properties. The reduced deformability of HbS-containing RBCs, along with the stiffening of sickle-shaped RBCs, impedes their passage through small vessels, potentially causing blockages in capillaries and obstructing microcirculation, leading to the particularly painful vaso-occlusive crisis (VOC).
In patients with SCD, physical exercise has been shown to be physiologically stressful, resulting in severe exercise intolerance.
Exercise limitations in SCD are related to anaemia, as walking for 5 minutes at 5 km/h leads to large elevations in heart rate (~175 beats/min) and blood lactate concentration (6.6 ± 0.4 mmol/L) in patients. This indicates that exercise, which is relatively easy for sedentary healthy adults, is already too difficult for patients with SCD. Additionally, the first lactate threshold is around 30-35 W for women and 44-50 W for men. These extremely low values reflect the significantly reduced physical ability of patients with SCD, suggesting that even common daily tasks are challenging for them.
The National Sports Health Strategy (SNSS) promotes physical activity for chronic conditions, including SCD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
盲法说明
Randomization will be in a 1:2 ratio between the untrained and trained arms, respectively. Randomization will be stratified on treatment by hydroxyurea, gender and age.
入排标准
- 年龄范围
- 15 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged over 15 years and 3 months
- •Male or female
- •Patients with sickle cell disease (HbSS or HbS-βthal0)
- •Affiliated to a social security system
- •Having freely given their written consent after having been informed of the purpose, the procedure and the potential risks involved
- •Patients in stabilised condition at the start of the experiment: at least 1 month after an acute chronic event or at least 3 months after a blood transfusion.
- •Patients hospitalised for vaso-occlusive crisis at least once in the last 3 years
排除标准
- •Patient whose adherence to the protocol is unlikely according to the investigator
- •Patients who already partake in regular physical activity (more than 1 hour of moderate-intensity physical activity per week)
- •Patients with a chronic inflammatory and/or infectious pathology
- •Patients with an intercurrent condition unresolved for less than a month
- •Patients hospitalised for cardiac decompensation during the last 12 months
- •Patients on anticoagulant treatment or with a pacemaker/defibrillator
- •Pregnant patients / breastfeeding woman
- •Patients deprived of liberty by judicial or administrative decision or patient under guardianship
- •Patients unable to understand the objectives and conditions of the study and unable to give cons
结局指标
主要结局
Number of vaso-occlusive crises (VOCs) with hospitalisation
时间窗: 12 months
determine the hospitalization rate for vaso-occlusive crisis
Exercise capacity and muscle metabolism and characteristics
时间窗: 12 months
the change from baseline in the workload at first lactate threshold. A blood sample (7 µL) will be taken from the earlobe and immediately analysed (in less than 20 seconds, Lactate Scout+, EKF Diagnostics) to determine the blood lactate concentration (\[lactate\]b). Exercise should be stopped when a \[lactate\]b of 4 mmol/L is reached
次要结局
- Duration of hospitalisation(12 months)
- Analgesic intake(12 months)
- Median time from the initiation of "treatment" (training or habitual (inactive) lifestyle) to the first and second hospitalised VOC(12 months)
- Days of school and job absenteeism(12 months)
- Number of acute chest syndromes (ACS)(12 months)
- 6-minute walk test (6MWT) - performed(12 months)
- Exercise Physiology Parameters(12 months)
- Echocardiographic Parameters(12 months)