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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Each training session will last 45 min. Exercise will start by a 5-min warm-up cycling period, followed by 30 min of cycling at the power output (W) individually determined before and corresponding to the first lactate threshold corresponding approximately to 2.5 mmol/l . Then patients will cool down for 5 min. Finally, the training sessions will end by 5 min of light stretching. All training sessions will take place at the hospital and will be under the supervision of a physician. Heart rate, oxygen saturation and blood lactate concentrations will be regularly measured. Work rate will be adjusted according to the obtained results. As a safety procedure, blood lactate concentration must not exceed 4 mmol/L during the training sessions. A particular attention will be paid to the hydration of patients. Pain and fatigue will be evaluated everyday by the patients using (100 mm) visual analog scales.
Hopital Avicenne
Bobigny, France
Centre hospitalier sud francilien
Corbeil-Essonnes, France
CHU Henri MONDOR
Créteil, France
CHU Kremlin-Bicêtre
Le Kremlin-Bicêtre, France
Hopital Europeen Georges POMPIDOU
Paris, France
Hopital Necker
Paris, France
Hopital Tenon
Paris, France
Centre hospitalier de Saint-Denis
Saint-Denis, France
CHU de SAINT-ETIENNE
Saint-Etienne, France
Power output (W) associated with the 4 mmol/L blood lactate concentration
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
Time frame: 8 weeks
Muscle fiber types distribution (%)
Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
Time frame: 8 weeks
perimeter (µm) of muscle fiber
Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
Time frame: 8 weeks
surface area (µm2) of muscle fiber
Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
Time frame: 8 weeks
satellite cell account
Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
Time frame: 8 weeks
Creatine Kinase (CK) of muscle
Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
Time frame: 8 weeks
Phosphofructokinase (PFK) of muscle
Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
Time frame: 8 weeks
Citrate Synthetase (CS) of muscle
Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
Time frame: 8 weeks
HAD (µmol/min/g dry muscle) of muscle
Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
Time frame: 8 weeks
COx (arbitrary unit, a.u.) of muscle
Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
Time frame: 8 weeks
Lactate Dehydrogenase (LDH) of muscle
Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
Time frame: 8 weeks
isoforms (%) of muscle
Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
Time frame: 8 weeks
Number of capillaries per mm2 (capillary density) and in contact with a muscle fiber
Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
Time frame: 8 weeks
surface area of microvessels (µm2)
Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
Time frame: 8 weeks
diameter of microvessels (µm)
Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
Time frame: 8 weeks
capillary tortuosity (quotient)
Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
Time frame: 8 weeks
expired volume (VE)
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.
Time frame: 8 weeks
oxygen consumption (VO2)
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.
Time frame: 8 weeks
carbon dioxide production (VCO2) (L/min)
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.
Time frame: 8 weeks
respiratory quotient (QR)
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.
Time frame: 8 weeks
Heart Rate (HR) (min-1)
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.
Time frame: 8 weeks
lactate level (mmol/l) at the end of submaximal incremental exercise
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.
Time frame: 8 weeks
Pulmonary volumes (L)
The volumes are measured by plethysmography
Time frame: 8 weeks
Performance to the six minute walk test (m)
Time frame: 8 weeks
Index of muscular blood flow and tissular oxygenation at rest (%)
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.
Time frame: 8 weeks
Index of exercise using Near-infrared reflectance spectroscopy (NIRS) (%)
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.
Time frame: 8 weeks
Maximal voluntary contraction (N)
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.
Time frame: 8 weeks
Neuromuscular fatigability (%)
It is measured in the same time that MVC
Time frame: 8 weeks
Quality of life : Scores to the Short Form 36 (SF-36)
Time frame: 8 weeks
Quality of life : Functional Assessment of Cancer Therapy (FACT Fatigue Part)
Time frame: 8 weeks
Quality of life : State-Trait Anxiety Scale (STAI Y-A)
Time frame: 8 weeks
Quality of life : Physical Self-Description Questionnaire( PSDQ)
Time frame: 8 weeks
Complete blood count and biochemical analyses (ionogram, urea, creatinine, LDH, creatine phosphokinase (CPK), aspartate aminotransferase ; usual units)
Patients will be subjected to blood samplings
Time frame: 8 weeks
Blood and plasma viscosity (centipoise)
Patients will be subjected to blood samplings
Time frame: 8 weeks
Erythrocyte deformability (%)
Patients will be subjected to blood samplings
Time frame: 8 weeks
aggregation properties (a.u.)
Patients will be subjected to blood samplings
Time frame: 8 weeks
dense red blood cells (%)
Patients will be subjected to blood samplings
Time frame: 8 weeks
Plasma analyses of adhesion molecules and markers of inflammation
Patients will be subjected to blood samplings
Time frame: 8 weeks
oxidative stress
Patients will be subjected to blood samplings
Time frame: 8 weeks
NO metabolism (µmol/L)
Patients will be subjected to blood samplings
Time frame: 8 weeks
Activity of antioxidant enzymes (µmol/L/min)
Patients will be subjected to blood samplings
Time frame: 8 weeks
Expression of erythrocytes membrane proteins (u.a.)
Patients will be subjected to blood samplings
Time frame: 8 weeks
Red blood cell (RBC) adhesion to endothelial cells (count of adhering RBC /mm²)
Patients will be subjected to blood samplings
Time frame: 8 weeks
Various hemodynamic criteria using echocardiography at rest and exercise
Time frame: 8 weeks
vaso-occlusive crises and acute chest syndrome
During the 8 weeks, all vaso-occlusive crises and acute chest syndrome will be collected
Time frame: 8 weeks
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