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
- 9
- 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,
研究组 & 干预措施
Training Program
The treatment will consist in an endurance training program. Only patients of the trained group will be subjected to this training program which will typically consist in 3 training sessions per week during 8 weeks i.e., 24 training sessions. Each training session will last 45 min. All training sessions will take place at the hospital and will be under medical supervision.
干预措施: Training Program (Other)
No Training Program
It will be asked to the control patients to not change their habitual physical activity during the entire period of observation
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
- diameter of microvessels (µm)(8 weeks)
- Quality of life : Functional Assessment of Cancer Therapy (FACT Fatigue Part)(8 weeks)
- aggregation properties (a.u.)(8 weeks)
- Citrate Synthetase (CS) of muscle(8 weeks)
- COx (arbitrary unit, a.u.) of muscle(8 weeks)
- Performance to the six minute walk test (m)(8 weeks)
- Plasma analyses of adhesion molecules and markers of inflammation(8 weeks)
- surface area (µm2) of muscle fiber(8 weeks)
- Expression of erythrocytes membrane proteins (u.a.)(8 weeks)
- dense red blood cells (%)(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)
- Lactate Dehydrogenase (LDH) of muscle(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)
- 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)
- Index of exercise using Near-infrared reflectance spectroscopy (NIRS) (%)(8 weeks)
- capillary tortuosity (quotient)(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)
- 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)
- vaso-occlusive crises and acute chest syndrome(8 weeks)
- respiratory quotient (QR)(8 weeks)
- Quality of life : Physical Self-Description Questionnaire( PSDQ)(8 weeks)