Evaluation of a Training Program for Homozygous Sickle Cell Disease Patients
- Conditions
- Hemoglobin S DiseaseSickle Cell Hemoglobin C Disease
- Interventions
- Other: Training Program
- Registration Number
- NCT02571088
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 40
- 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.
- 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,
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Training Program 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.
- Primary Outcome Measures
Name Time Method Power output (W) associated with the 4 mmol/L blood lactate concentration 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
- Secondary Outcome Measures
Name Time Method Citrate Synthetase (CS) of muscle 8 weeks Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
COx (arbitrary unit, a.u.) of muscle 8 weeks Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
surface area (µm2) of muscle fiber 8 weeks Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
dense red blood cells (%) 8 weeks Patients will be subjected to blood samplings
Plasma analyses of adhesion molecules and markers of inflammation 8 weeks Patients will be subjected to blood samplings
Expression of erythrocytes membrane proteins (u.a.) 8 weeks Patients will be subjected to blood samplings
oxygen consumption (VO2) 8 weeks Patients will perform a submaximal incremental exercise on a cycle ergometer. Exercise will start at 20 W and 30 W for females and males, respectively. After 2 minutes at this load, and every 2 minutes thereafter, work rate will increase by 10 W and 15 W for females and males, respectively. Total exercise duration is expected to be within 8 to 14 minutes.
diameter of microvessels (µm) 8 weeks Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
carbon dioxide production (VCO2) (L/min) 8 weeks Patients will perform a submaximal incremental exercise on a cycle ergometer. Exercise will start at 20 W and 30 W for females and males, respectively. After 2 minutes at this load, and every 2 minutes thereafter, work rate will increase by 10 W and 15 W for females and males, respectively. Total exercise duration is expected to be within 8 to 14 minutes.
oxidative stress 8 weeks Patients will be subjected to blood samplings
NO metabolism (µmol/L) 8 weeks Patients will be subjected to blood samplings
capillary tortuosity (quotient) 8 weeks Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
Activity of antioxidant enzymes (µmol/L/min) 8 weeks Patients will be subjected to blood samplings
Red blood cell (RBC) adhesion to endothelial cells (count of adhering RBC /mm²) 8 weeks Patients will be subjected to blood samplings
Various hemodynamic criteria using echocardiography at rest and exercise 8 weeks expired volume (VE) 8 weeks Patients will perform a submaximal incremental exercise on a cycle ergometer. Exercise will start at 20 W and 30 W for females and males, respectively. After 2 minutes at this load, and every 2 minutes thereafter, work rate will increase by 10 W and 15 W for females and males, respectively. Total exercise duration is expected to be within 8 to 14 minutes.
Neuromuscular fatigability (%) 8 weeks It is measured in the same time that MVC
Quality of life : Scores to the Short Form 36 (SF-36) 8 weeks Muscle fiber types distribution (%) 8 weeks Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
perimeter (µm) of muscle fiber 8 weeks Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
satellite cell account 8 weeks Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
Creatine Kinase (CK) of muscle 8 weeks Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
Phosphofructokinase (PFK) of muscle 8 weeks Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
Lactate Dehydrogenase (LDH) of muscle 8 weeks Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
Quality of life : State-Trait Anxiety Scale (STAI Y-A) 8 weeks HAD (µmol/min/g dry muscle) of muscle 8 weeks Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
isoforms (%) of muscle 8 weeks Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
Number of capillaries per mm2 (capillary density) and in contact with a muscle fiber 8 weeks Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
surface area of microvessels (µm2) 8 weeks Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
Heart Rate (HR) (min-1) 8 weeks Patients will perform a submaximal incremental exercise on a cycle ergometer. Exercise will start at 20 W and 30 W for females and males, respectively. After 2 minutes at this load, and every 2 minutes thereafter, work rate will increase by 10 W and 15 W for females and males, respectively. Total exercise duration is expected to be within 8 to 14 minutes.
lactate level (mmol/l) at the end of submaximal incremental exercise 8 weeks Patients will perform a submaximal incremental exercise on a cycle ergometer. Exercise will start at 20 W and 30 W for females and males, respectively. After 2 minutes at this load, and every 2 minutes thereafter, work rate will increase by 10 W and 15 W for females and males, respectively. Total exercise duration is expected to be within 8 to 14 minutes.
Index of muscular blood flow and tissular oxygenation at rest (%) 8 weeks Patients will perform a submaximal incremental exercise on a cycle ergometer. Exercise will start at 20 W and 30 W for females and males, respectively. After 2 minutes at this load, and every 2 minutes thereafter, work rate will increase by 10 W and 15 W for females and males, respectively. Total exercise duration is expected to be within 8 to 14 minutes.
Pulmonary volumes (L) 8 weeks The volumes are measured by plethysmography
Performance to the six minute walk test (m) 8 weeks Index of exercise using Near-infrared reflectance spectroscopy (NIRS) (%) 8 weeks Patients will perform a submaximal incremental exercise on a cycle ergometer. Exercise will start at 20 W and 30 W for females and males, respectively. After 2 minutes at this load, and every 2 minutes thereafter, work rate will increase by 10 W and 15 W for females and males, respectively. Total exercise duration is expected to be within 8 to 14 minutes.
Quality of life : Functional Assessment of Cancer Therapy (FACT Fatigue Part) 8 weeks Maximal voluntary contraction (N) 8 weeks Maximal Voluntary Contraction (MVC) will be measured 3 times 1 min apart to determine an initial MVC. After 10 min of rest following the MVC trials, neuromuscular fatigability will be assess by repetition of series of 10 submaximal contractions (of 4 s separated by 5 s) followed by a MVC trial until a decrease of 25% of the initial MVC is observed. No more than 7 series will be performed, even if the 25% decrease of initial MVC is not observed.
Complete blood count and biochemical analyses (ionogram, urea, creatinine, LDH, creatine phosphokinase (CPK), aspartate aminotransferase ; usual units) 8 weeks Patients will be subjected to blood samplings
Blood and plasma viscosity (centipoise) 8 weeks Patients will be subjected to blood samplings
Erythrocyte deformability (%) 8 weeks Patients will be subjected to blood samplings
aggregation properties (a.u.) 8 weeks Patients will be subjected to blood samplings
vaso-occlusive crises and acute chest syndrome 8 weeks During the 8 weeks, all vaso-occlusive crises and acute chest syndrome will be collected
respiratory quotient (QR) 8 weeks Patients will perform a submaximal incremental exercise on a cycle ergometer. Exercise will start at 20 W and 30 W for females and males, respectively. After 2 minutes at this load, and every 2 minutes thereafter, work rate will increase by 10 W and 15 W for females and males, respectively. Total exercise duration is expected to be within 8 to 14 minutes.
Quality of life : Physical Self-Description Questionnaire( PSDQ) 8 weeks
Trial Locations
- Locations (9)
Hopital Avicenne
🇫🇷Bobigny, France
Hopital Necker
🇫🇷Paris, France
Centre hospitalier de Saint-Denis
🇫🇷Saint-denis, France
CHU de SAINT-ETIENNE
🇫🇷Saint-etienne, France
Hopital Tenon
🇫🇷Paris, France
Centre hospitalier sud francilien
🇫🇷Corbeil-essonnes, France
CHU Henri MONDOR
🇫🇷Creteil, France
Hopital Europeen Georges POMPIDOU
🇫🇷Paris, France
CHU Kremlin-Bicêtre
🇫🇷Le Kremlin Bicetre, France