Evaluation of a Training Program for Homozygous Sickle Cell Disease Patients: Benefits on Physical Ability and Skeletal Muscle. An Interventional Pilot, Multicentric, Prospective, Longitudinal Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 18
- 主要终点
- Power output (W) associated with the 4 mmol/L blood lactate concentration
研究概览
简要总结
Sickle cell disease (SCD) is the most frequent inherited disease in the world. Literature reports that SCD patients display intolerance to exercise, important muscle weakness and profound remodeling of skeletal muscle including amyotrophy and rarefied microvascular network.
Because strenuous exercise induces acidosis, hemorheological alterations, endothelial activation and oxidative stress, it constitutes a potential triggering factor of sickling and vaso-occlusive crisis. As a consequence, physical activity is usually discouraged in patients with SCD. However, moderate and regular physical activity seems to be not only safe but also beneficial for SCD patients.
详细描述
Besides, endurance training is known to induce moderate muscle hypertrophy and increase microvascular network. Therefore, adapted, moderate and regular physical activity appears as a potential strategy able to improve muscle function, decrease symptoms of the disease and improve autonomy and quality of life of patients with SCD. However, it remains necessary to define the modalities of exercise therapy in SCD and to objectively evaluate the risks, limitations and gains on physical ability, muscle function and quality of life in patients with SCD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Sickle cell disease patient (HbSS or HbS-βthal0),
- •Affiliated to a Health Security program,
- •Consent form signed,
- •Patients in stabilized state at the onset of the experiment: at least one month after an acute adverse event and at least 3 months after a blood transfusion.
排除标准
- •Patients whom adhesion/compliance to the protocol appears uncertain,
- •Patient involved in another clinical trial or within the exclusion period of a previous clinical trial,
- •Patients known to be affected by a chronic inflammatory or infectious pathology,
- •Patients having an intercurrent infection, especially inflammatory, unsolved since less than one month,
- •Patients with clinical signs of heart failure or hospitalized for cardiac decompensation during the past 12 months,
- •Patients with left ventricular ejection fraction < 50%, pulmonary arterial hypertension with tricuspid regurgitation velocity > 2.5 m/s, atrial fibrillation, ventricular rhythm disorders during exercise, left ventricular hypertrophy (septal to lateral wall thickness ≥ 10 mm), significant valvulopathy, established coronary disease, uncontrolled hypertension,
- •Patients with a treatment against cardiac arrhythmia or altering sino-atrial node activity (beta-blockers, atropine, sympathomimetic agents...),
- •Patients under anti-coagulant treatment,
- •Patients with pacemaker or defibrillator,
- •Body Mass Index (BMI) > 35,
- •Patients with hip osteonecrosis,
- •Patients with cerebral vasculopathy or history of stroke (cerebrovascular attack) with epilepsy,
- •Pregnant or lactating patients,
- •Homeless patients,
- •Patients with the inability to understand the aims,
结局指标
主要结局
Power output (W) associated with the 4 mmol/L blood lactate concentration
时间窗: 8 weeks
The blood lactate concentration curve in response to incremental exercise depends on the physical ability of patients. Endurance training is known to increase the power output (W) associated with a given blood lactate concentration. For the present study, we used the 4 mmol/L blood lactate concentration as a remarkable/singular point of the curve
次要结局
- Citrate Synthetase (CS) of muscle(8 weeks)
- COx (arbitrary unit, a.u.) of muscle(8 weeks)
- surface area (µm2) of muscle fiber(8 weeks)
- dense red blood cells (%)(8 weeks)
- Plasma analyses of adhesion molecules and markers of inflammation(8 weeks)
- Expression of erythrocytes membrane proteins (u.a.)(8 weeks)
- oxygen consumption (VO2)(8 weeks)
- carbon dioxide production (VCO2) (L/min)(8 weeks)
- oxidative stress(8 weeks)
- NO metabolism (µmol/L)(8 weeks)
- Activity of antioxidant enzymes (µmol/L/min)(8 weeks)
- Red blood cell (RBC) adhesion to endothelial cells (count of adhering RBC /mm²)(8 weeks)
- Various hemodynamic criteria using echocardiography at rest and exercise(8 weeks)
- Neuromuscular fatigability (%)(8 weeks)
- Quality of life : Scores to the Short Form 36 (SF-36)(8 weeks)
- Muscle fiber types distribution (%)(8 weeks)
- perimeter (µm) of muscle fiber(8 weeks)
- satellite cell account(8 weeks)
- Creatine Kinase (CK) of muscle(8 weeks)
- Phosphofructokinase (PFK) of muscle(8 weeks)
- Lactate Dehydrogenase (LDH) of muscle(8 weeks)
- diameter of microvessels (µm)(8 weeks)
- Quality of life : State-Trait Anxiety Scale (STAI Y-A)(8 weeks)
- HAD (µmol/min/g dry muscle) of muscle(8 weeks)
- isoforms (%) of muscle(8 weeks)
- Number of capillaries per mm2 (capillary density) and in contact with a muscle fiber(8 weeks)
- surface area of microvessels (µm2)(8 weeks)
- capillary tortuosity (quotient)(8 weeks)
- Quality of life : Functional Assessment of Cancer Therapy (FACT Fatigue Part)(8 weeks)
- expired volume (VE)(8 weeks)
- Heart Rate (HR) (min-1)(8 weeks)
- lactate level (mmol/l) at the end of submaximal incremental exercise(8 weeks)
- Index of muscular blood flow and tissular oxygenation at rest (%)(8 weeks)
- Pulmonary volumes (L)(8 weeks)
- Performance to the six minute walk test (m)(8 weeks)
- Index of exercise using Near-infrared reflectance spectroscopy (NIRS) (%)(8 weeks)
- Erythrocyte deformability (%)(8 weeks)
- Maximal voluntary contraction (N)(8 weeks)
- Complete blood count and biochemical analyses (ionogram, urea, creatinine, LDH, creatine phosphokinase (CPK), aspartate aminotransferase ; usual units)(8 weeks)
- Blood and plasma viscosity (centipoise)(8 weeks)
- aggregation properties (a.u.)(8 weeks)
- vaso-occlusive crises and acute chest syndrome(8 weeks)
- respiratory quotient (QR)(8 weeks)
- Quality of life : Physical Self-Description Questionnaire( PSDQ)(8 weeks)