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| ID | Type | Description | Link |
|---|---|---|---|
| 2014-A00334-43 | Other Identifier | ANSM |
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| Name | Class |
|---|---|
| Centre de Référence des Syndromes Drépanocytaires Majeurs | OTHER |
| Laboratoire de Physiologie de l'Exercice | UNKNOWN |
| Claude Bernard University | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Training Program | Experimental | 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. |
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| No Training Program | No Intervention | It will be asked to the control patients to not change their habitual physical activity during the entire period of observation |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Training Program | Other | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 8 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Muscle fiber types distribution (%) | Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg). | 8 weeks |
| perimeter (µm) of muscle fiber | Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Leonard FEASSON, MD | CHU de SAINT-ETIENNE | Principal Investigator |
| Laurent MESSONIER, PhD | Université de Savoie | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hopital Avicenne | Bobigny | 93000 | France | |||
| Centre hospitalier sud francilien |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32681734 | Derived | Merlet AN, Feasson L, Bartolucci P, Hourde C, Schwalm C, Gellen B, Galacteros F, Deldicque L, Francaux M, Messonnier LA; EXDRE Collaborative Study Group. Muscle structural, energetic and functional benefits of endurance exercise training in sickle cell disease. Am J Hematol. 2020 Nov;95(11):1257-1268. doi: 10.1002/ajh.25936. Epub 2020 Aug 1. | |
| 31742587 |
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| ID | Term |
|---|---|
| D006450 | Hemoglobin SC Disease |
| D000755 | Anemia, Sickle Cell |
| ID | Term |
|---|---|
| D000745 | Anemia, Hemolytic, Congenital |
| D000743 | Anemia, Hemolytic |
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
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| 8 weeks |
| surface area (µm2) of muscle fiber | Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg). | 8 weeks |
| satellite cell account | Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg). | 8 weeks |
| Creatine Kinase (CK) of muscle | Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg). | 8 weeks |
| Phosphofructokinase (PFK) of muscle | Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg). | 8 weeks |
| Citrate Synthetase (CS) of muscle | Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg). | 8 weeks |
| HAD (µmol/min/g dry muscle) of muscle | Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg). | 8 weeks |
| COx (arbitrary unit, a.u.) of muscle | Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg). | 8 weeks |
| Lactate Dehydrogenase (LDH) of muscle | Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg). | 8 weeks |
| isoforms (%) of muscle | Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg). | 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). | 8 weeks |
| surface area of microvessels (µm2) | Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg). | 8 weeks |
| diameter of microvessels (µm) | Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg). | 8 weeks |
| capillary tortuosity (quotient) | Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg). | 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. | 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. | 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. | 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. | 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. | 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. | 8 weeks |
| Pulmonary volumes (L) | The volumes are measured by plethysmography | 8 weeks |
| Performance to the six minute walk test (m) | 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. | 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. | 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. | 8 weeks |
| Neuromuscular fatigability (%) | It is measured in the same time that MVC | 8 weeks |
| Quality of life : Scores to the Short Form 36 (SF-36) | 8 weeks |
| Quality of life : Functional Assessment of Cancer Therapy (FACT Fatigue Part) | 8 weeks |
| Quality of life : State-Trait Anxiety Scale (STAI Y-A) | 8 weeks |
| Quality of life : Physical Self-Description Questionnaire( PSDQ) | 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 | 8 weeks |
| Blood and plasma viscosity (centipoise) | Patients will be subjected to blood samplings | 8 weeks |
| Erythrocyte deformability (%) | Patients will be subjected to blood samplings | 8 weeks |
| aggregation properties (a.u.) | Patients will be subjected to blood samplings | 8 weeks |
| dense red blood cells (%) | Patients will be subjected to blood samplings | 8 weeks |
| Plasma analyses of adhesion molecules and markers of inflammation | Patients will be subjected to blood samplings | 8 weeks |
| oxidative stress | Patients will be subjected to blood samplings | 8 weeks |
| NO metabolism (µmol/L) | Patients will be subjected to blood samplings | 8 weeks |
| Activity of antioxidant enzymes (µmol/L/min) | Patients will be subjected to blood samplings | 8 weeks |
| Expression of erythrocytes membrane proteins (u.a.) | Patients will be subjected to blood samplings | 8 weeks |
| Red blood cell (RBC) adhesion to endothelial cells (count of adhering RBC /mm²) | Patients will be subjected to blood samplings | 8 weeks |
| Various hemodynamic criteria using echocardiography at rest and exercise | 8 weeks |
| vaso-occlusive crises and acute chest syndrome | During the 8 weeks, all vaso-occlusive crises and acute chest syndrome will be collected | 8 weeks |
| Corbeil-Essonnes |
| 91100 |
| France |
| CHU Henri MONDOR | Créteil | 94010 | France |
| CHU Kremlin-Bicêtre | Le Kremlin-Bicêtre | 93270 | France |
| Hopital Europeen Georges POMPIDOU | Paris | 75015 | France |
| Hopital Necker | Paris | 75015 | France |
| Hopital Tenon | Paris | 75020 | France |
| Centre hospitalier de Saint-Denis | Saint-Denis | 93200 | France |
| CHU de SAINT-ETIENNE | Saint-Etienne | 42000 | France |
| Merlet AN, Messonnier LA, Coudy-Gandilhon C, Bechet D, Gellen B, Rupp T, Galacteros F, Bartolucci P, Feasson L. Beneficial effects of endurance exercise training on skeletal muscle microvasculature in sickle cell disease patients. Blood. 2019 Dec 19;134(25):2233-2241. doi: 10.1182/blood.2019001055. |
| 30389037 | Derived | Gellen B, Messonnier LA, Galacteros F, Audureau E, Merlet AN, Rupp T, Peyrot S, Martin C, Feasson L, Bartolucci P; EXDRE collaborative study group. Moderate-intensity endurance-exercise training in patients with sickle-cell disease without severe chronic complications (EXDRE): an open-label randomised controlled trial. Lancet Haematol. 2018 Nov;5(11):e554-e562. doi: 10.1016/S2352-3026(18)30163-7. |
| D006425 |
| Hemic and Lymphatic Diseases |
| D006453 | Hemoglobinopathies |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |