Evaluation of a Training Program for Homozygous Sickle Cell Disease Patients

Hemoglobin S Disease Clinical Trial

— EXDRE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02571088
• Other study ID #: 1408030
• Secondary ID: 2014-A00334-43
• Status: Completed
• Phase: N/A
• Start date: September 2014
• Est. completion date: April 2016

Study information

• Verified date: September 2021
• Source: Centre Hospitalier Universitaire de Saint Etienne
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: April 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Sickle cell disease patient (HbSS or HbS-ßthal0),

• 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,

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Hemoglobin S Disease
• Hemoglobin SC Disease
• Sickle Cell Hemoglobin C Disease
• Sickle Cell Trait

Intervention

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.

Locations

Country	Name	City	State
France	Hopital Avicenne	Bobigny
France	Centre hospitalier sud francilien	Corbeil-essonnes
France	CHU Henri MONDOR	Creteil
France	CHU Kremlin-Bicêtre	Le Kremlin Bicetre
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

Sponsors (4)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Saint Etienne	Centre de Référence des Syndromes Drépanocytaires Majeurs, Claude Bernard University, Laboratoire de Physiologie de l'Exercice

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Secondary	Muscle fiber types distribution (%)	Patients will be subjected to a biopsy of the vastus lateralis muscle (˜ 200 mg).	8 weeks
Secondary	perimeter (µm) of muscle fiber	Patients will be subjected to a biopsy of the vastus lateralis muscle (˜ 200 mg).	8 weeks
Secondary	surface area (µm2) of muscle fiber	Patients will be subjected to a biopsy of the vastus lateralis muscle (˜ 200 mg).	8 weeks
Secondary	satellite cell account	Patients will be subjected to a biopsy of the vastus lateralis muscle (˜ 200 mg).	8 weeks
Secondary	Creatine Kinase (CK) of muscle	Patients will be subjected to a biopsy of the vastus lateralis muscle (˜ 200 mg).	8 weeks
Secondary	Phosphofructokinase (PFK) of muscle	Patients will be subjected to a biopsy of the vastus lateralis muscle (˜ 200 mg).	8 weeks
Secondary	Citrate Synthetase (CS) of muscle	Patients will be subjected to a biopsy of the vastus lateralis muscle (˜ 200 mg).	8 weeks
Secondary	HAD (µmol/min/g dry muscle) of muscle	Patients will be subjected to a biopsy of the vastus lateralis muscle (˜ 200 mg).	8 weeks
Secondary	COx (arbitrary unit, a.u.) of muscle	Patients will be subjected to a biopsy of the vastus lateralis muscle (˜ 200 mg).	8 weeks
Secondary	Lactate Dehydrogenase (LDH) of muscle	Patients will be subjected to a biopsy of the vastus lateralis muscle (˜ 200 mg).	8 weeks
Secondary	isoforms (%) of muscle	Patients will be subjected to a biopsy of the vastus lateralis muscle (˜ 200 mg).	8 weeks
Secondary	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
Secondary	surface area of microvessels (µm2)	Patients will be subjected to a biopsy of the vastus lateralis muscle (˜ 200 mg).	8 weeks
Secondary	diameter of microvessels (µm)	Patients will be subjected to a biopsy of the vastus lateralis muscle (˜ 200 mg).	8 weeks
Secondary	capillary tortuosity (quotient)	Patients will be subjected to a biopsy of the vastus lateralis muscle (˜ 200 mg).	8 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Pulmonary volumes (L)	The volumes are measured by plethysmography	8 weeks
Secondary	Performance to the six minute walk test (m)		8 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	Neuromuscular fatigability (%)	It is measured in the same time that MVC	8 weeks
Secondary	Quality of life : Scores to the Short Form 36 (SF-36)		8 weeks
Secondary	Quality of life : Functional Assessment of Cancer Therapy (FACT Fatigue Part)		8 weeks
Secondary	Quality of life : State-Trait Anxiety Scale (STAI Y-A)		8 weeks
Secondary	Quality of life : Physical Self-Description Questionnaire( PSDQ)		8 weeks
Secondary	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
Secondary	Blood and plasma viscosity (centipoise)	Patients will be subjected to blood samplings	8 weeks
Secondary	Erythrocyte deformability (%)	Patients will be subjected to blood samplings	8 weeks
Secondary	aggregation properties (a.u.)	Patients will be subjected to blood samplings	8 weeks
Secondary	dense red blood cells (%)	Patients will be subjected to blood samplings	8 weeks
Secondary	Plasma analyses of adhesion molecules and markers of inflammation	Patients will be subjected to blood samplings	8 weeks
Secondary	oxidative stress	Patients will be subjected to blood samplings	8 weeks
Secondary	NO metabolism (µmol/L)	Patients will be subjected to blood samplings	8 weeks
Secondary	Activity of antioxidant enzymes (µmol/L/min)	Patients will be subjected to blood samplings	8 weeks
Secondary	Expression of erythrocytes membrane proteins (u.a.)	Patients will be subjected to blood samplings	8 weeks
Secondary	Red blood cell (RBC) adhesion to endothelial cells (count of adhering RBC /mm²)	Patients will be subjected to blood samplings	8 weeks
Secondary	Various hemodynamic criteria using echocardiography at rest and exercise		8 weeks
Secondary	vaso-occlusive crises and acute chest syndrome	During the 8 weeks, all vaso-occlusive crises and acute chest syndrome will be collected	8 weeks