Evaluation of a Training Program for Homozygous Sickle Cell Disease Patients (EXDRE)
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ClinicalTrials.gov Identifier: NCT02571088 |
Recruitment Status :
Completed
First Posted : October 8, 2015
Last Update Posted : September 13, 2021
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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.
Condition or disease | Intervention/treatment | Phase |
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Sickle Cell Hemoglobin C Disease Hemoglobin S Disease | Other: Training Program | Not Applicable |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 40 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | 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 |
Study Start Date : | September 2014 |
Actual Primary Completion Date : | April 2016 |
Actual Study Completion Date : | April 2016 |

Arm | Intervention/treatment |
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Experimental: 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.
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Other: Training Program
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. |
No Intervention: No Training Program
It will be asked to the control patients to not change their habitual physical activity during the entire period of observation
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- Power output (W) associated with the 4 mmol/L blood lactate concentration [ Time Frame: 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
- Muscle fiber types distribution (%) [ Time Frame: 8 weeks ]Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
- perimeter (µm) of muscle fiber [ Time Frame: 8 weeks ]Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
- surface area (µm2) of muscle fiber [ Time Frame: 8 weeks ]Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
- satellite cell account [ Time Frame: 8 weeks ]Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
- Creatine Kinase (CK) of muscle [ Time Frame: 8 weeks ]Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
- Phosphofructokinase (PFK) of muscle [ Time Frame: 8 weeks ]Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
- Citrate Synthetase (CS) of muscle [ Time Frame: 8 weeks ]Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
- HAD (µmol/min/g dry muscle) of muscle [ Time Frame: 8 weeks ]Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
- COx (arbitrary unit, a.u.) of muscle [ Time Frame: 8 weeks ]Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
- Lactate Dehydrogenase (LDH) of muscle [ Time Frame: 8 weeks ]Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
- isoforms (%) of muscle [ Time Frame: 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 [ Time Frame: 8 weeks ]Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
- surface area of microvessels (µm2) [ Time Frame: 8 weeks ]Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
- diameter of microvessels (µm) [ Time Frame: 8 weeks ]Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
- capillary tortuosity (quotient) [ Time Frame: 8 weeks ]Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
- expired volume (VE) [ Time Frame: 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.
- oxygen consumption (VO2) [ Time Frame: 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.
- carbon dioxide production (VCO2) (L/min) [ Time Frame: 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.
- respiratory quotient (QR) [ Time Frame: 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.
- Heart Rate (HR) (min-1) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 8 weeks ]The volumes are measured by plethysmography
- Performance to the six minute walk test (m) [ Time Frame: 8 weeks ]
- Index of muscular blood flow and tissular oxygenation at rest (%) [ Time Frame: 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 exercise using Near-infrared reflectance spectroscopy (NIRS) (%) [ Time Frame: 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.
- Maximal voluntary contraction (N) [ Time Frame: 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.
- Neuromuscular fatigability (%) [ Time Frame: 8 weeks ]It is measured in the same time that MVC
- 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) [ Time Frame: 8 weeks ]Patients will be subjected to blood samplings
- Blood and plasma viscosity (centipoise) [ Time Frame: 8 weeks ]Patients will be subjected to blood samplings
- Erythrocyte deformability (%) [ Time Frame: 8 weeks ]Patients will be subjected to blood samplings
- aggregation properties (a.u.) [ Time Frame: 8 weeks ]Patients will be subjected to blood samplings
- dense red blood cells (%) [ Time Frame: 8 weeks ]Patients will be subjected to blood samplings
- Plasma analyses of adhesion molecules and markers of inflammation [ Time Frame: 8 weeks ]Patients will be subjected to blood samplings
- oxidative stress [ Time Frame: 8 weeks ]Patients will be subjected to blood samplings
- NO metabolism (µmol/L) [ Time Frame: 8 weeks ]Patients will be subjected to blood samplings
- Activity of antioxidant enzymes (µmol/L/min) [ Time Frame: 8 weeks ]Patients will be subjected to blood samplings
- Expression of erythrocytes membrane proteins (u.a.) [ Time Frame: 8 weeks ]Patients will be subjected to blood samplings
- Red blood cell (RBC) adhesion to endothelial cells (count of adhering RBC /mm²) [ Time Frame: 8 weeks ]Patients will be subjected to blood samplings
- Various hemodynamic criteria using echocardiography at rest and exercise [ Time Frame: 8 weeks ]
- vaso-occlusive crises and acute chest syndrome [ Time Frame: 8 weeks ]During the 8 weeks, all vaso-occlusive crises and acute chest syndrome will be collected

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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,

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02571088
France | |
Hopital Avicenne | |
Bobigny, France, 93000 | |
Centre hospitalier sud francilien | |
Corbeil-essonnes, France, 91100 | |
CHU Henri MONDOR | |
Creteil, France, 94010 | |
CHU Kremlin-Bicêtre | |
Le Kremlin Bicetre, France, 93270 | |
Hopital Europeen Georges POMPIDOU | |
Paris, France, 75015 | |
Hopital Necker | |
Paris, France, 75015 | |
Hopital Tenon | |
Paris, France, 75020 | |
Centre hospitalier de Saint-Denis | |
Saint-denis, France, 93200 | |
CHU de SAINT-ETIENNE | |
Saint-etienne, France, 42000 |
Principal Investigator: | Leonard FEASSON, MD | CHU de SAINT-ETIENNE | |
Study Director: | Laurent MESSONIER, PhD | Université de Savoie |
Responsible Party: | Centre Hospitalier Universitaire de Saint Etienne |
ClinicalTrials.gov Identifier: | NCT02571088 |
Other Study ID Numbers: |
1408030 2014-A00334-43 ( Other Identifier: ANSM ) |
First Posted: | October 8, 2015 Key Record Dates |
Last Update Posted: | September 13, 2021 |
Last Verified: | September 2021 |
Sickle Cell Hemoglobin C Disease Sports Training Hemoglobin S Disease Lactate |
Anemia, Sickle Cell Sickle Cell Trait Hemoglobin SC Disease Hemoglobin C Disease Anemia, Hemolytic, Congenital |
Anemia, Hemolytic Anemia Hematologic Diseases Hemoglobinopathies Genetic Diseases, Inborn |