Clinical trial NCT02571088: Evaluation of a Training Program for Homozygous Sickle Cell Disease Patients
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Sickle Cell Hemoglobin C Disease
Hemoglobin S Disease
Keywords: Sickle Cell Hemoglobin C Disease
Sports Training
Hemoglobin S Disease
Lactate
Lead sponsor: Centre Hospitalier Universitaire de Saint Etienne
Sponsor class: OTHER
Collaborators: name: Centre de Référence des Syndromes Drépanocytaires Majeurs
name: Laboratoire de Physiologie de l'Exercice
name: Claude Bernard University
First posted: 2015-10-08
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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,

Primary outcomes:
measure: Power output (W) associated with the 4 mmol/L blood lactate concentration
timeFrame: 8 weeks
Secondary outcomes:
measure: Muscle fiber types distribution (%)
timeFrame: 8 weeks
measure: perimeter (µm) of muscle fiber
timeFrame: 8 weeks
measure: surface area (µm2) of muscle fiber
timeFrame: 8 weeks
measure: satellite cell account
timeFrame: 8 weeks
measure: Creatine Kinase (CK) of muscle
timeFrame: 8 weeks
measure: Phosphofructokinase (PFK) of muscle
timeFrame: 8 weeks
measure: Citrate Synthetase (CS) of muscle
timeFrame: 8 weeks
measure: HAD (µmol/min/g dry muscle) of muscle
timeFrame: 8 weeks
measure: COx (arbitrary unit, a.u.) of muscle
timeFrame: 8 weeks
measure: Lactate Dehydrogenase (LDH) of muscle
timeFrame: 8 weeks
measure: isoforms (%) of muscle
timeFrame: 8 weeks
measure: Number of capillaries per mm2 (capillary density) and in contact with a muscle fiber
timeFrame: 8 weeks
measure: surface area of microvessels (µm2)
timeFrame: 8 weeks
measure: diameter of microvessels (µm)
timeFrame: 8 weeks
measure: capillary tortuosity (quotient)
timeFrame: 8 weeks
measure: expired volume (VE)
timeFrame: 8 weeks
measure: oxygen consumption (VO2)
timeFrame: 8 weeks
measure: carbon dioxide production (VCO2) (L/min)
timeFrame: 8 weeks
measure: respiratory quotient (QR)
timeFrame: 8 weeks
measure: Heart Rate (HR) (min-1)
timeFrame: 8 weeks
measure: lactate level (mmol/l) at the end of submaximal incremental exercise
timeFrame: 8 weeks
measure: Pulmonary volumes (L)
timeFrame: 8 weeks
measure: Performance to the six minute walk test (m)
timeFrame: 8 weeks
measure: Index of muscular blood flow and tissular oxygenation at rest (%)
timeFrame: 8 weeks
measure: Index of exercise using Near-infrared reflectance spectroscopy (NIRS) (%)
timeFrame: 8 weeks
measure: Maximal voluntary contraction (N)
timeFrame: 8 weeks
measure: Neuromuscular fatigability (%)
timeFrame: 8 weeks
measure: Quality of life : Scores to the Short Form 36 (SF-36)
timeFrame: 8 weeks
measure: Quality of life : Functional Assessment of Cancer Therapy (FACT Fatigue Part)
timeFrame: 8 weeks
measure: Quality of life : State-Trait Anxiety Scale (STAI Y-A)
timeFrame: 8 weeks
measure: Quality of life : Physical Self-Description Questionnaire( PSDQ)
timeFrame: 8 weeks
measure: Complete blood count and biochemical analyses (ionogram, urea, creatinine, LDH, creatine phosphokinase (CPK), aspartate aminotransferase ; usual units)
timeFrame: 8 weeks
measure: Blood and plasma viscosity (centipoise)
timeFrame: 8 weeks
measure: Erythrocyte deformability (%)
timeFrame: 8 weeks
measure: aggregation properties (a.u.)
timeFrame: 8 weeks
measure: dense red blood cells (%)
timeFrame: 8 weeks
measure: Plasma analyses of adhesion molecules and markers of inflammation
timeFrame: 8 weeks
measure: oxidative stress
timeFrame: 8 weeks
measure: NO metabolism (µmol/L)
timeFrame: 8 weeks
measure: Activity of antioxidant enzymes (µmol/L/min)
timeFrame: 8 weeks
measure: Expression of erythrocytes membrane proteins (u.a.)
timeFrame: 8 weeks
measure: Red blood cell (RBC) adhesion to endothelial cells (count of adhering RBC /mm²)
timeFrame: 8 weeks
measure: Various hemodynamic criteria using echocardiography at rest and exercise
timeFrame: 8 weeks
measure: vaso-occlusive crises and acute chest syndrome
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Bobigny
country: France
facility: Hopital Avicenne
city: Corbeil-essonnes
country: France
facility: Centre hospitalier sud francilien
city: Creteil
country: France
facility: CHU Henri MONDOR
city: Le Kremlin Bicetre
country: France
facility: CHU Kremlin-Bicêtre
city: Paris
country: France
facility: Hopital Europeen Georges POMPIDOU
city: Paris
country: France
facility: Hopital Necker
city: Paris
country: France
facility: Hopital Tenon
city: Saint-denis
country: France
facility: Centre hospitalier de Saint-Denis
city: Saint-etienne
country: France
facility: CHU de SAINT-ETIENNE
Study officials:
affiliation: CHU de SAINT-ETIENNE
name: Leonard FEASSON, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Université de Savoie
name: Laurent MESSONIER, PhD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.