Prospective Controlled Trial on Endurance Exercise Training in Adult Sickle Cell Disease Patients
Authors: Gellen Barnabas , Messonnier Laurent , Merlet Angele , Audureau Etienne , Rupp Thomas , Peyrot Sandrine , Martin Cyril , Ribeil Jean-Antoine , Arlet jean Benoit , Galactéros Frédéric , Feasson Leonard , Bartolucci Pablo 
Published: April 2021

Abstract

B Gellen and L Messonnier, and L Feasson and P Bartolucci equally contributed to this work
Introduction Sickle cell disease (SCD) is the most common inherited disease worldwide. Because favoring the risk of vaso-occlusive crises (VOC), SCD patients are banned from strenuous exercise. We hypothesized that a well-controlled moderate-intensity endurance exercise training (EET) program could improve SCD patients without provoking VOC.
Patients and Methods: Weconducted aprospective, multicenter, controlled study with individually tailored Blood lactate-guided (BL) endurance training on a cycloergometer for 8 weeks in adult SCD patients. The primary end point was the submaximal incremental cardio-pulmonary exercise testing (CPET) at a BL concentration of 4 mmol.L-1. Secondary endpoints were: CPET at a BL 2.5 mmol/L and at the first lactic threshold (LT1), BL levels at given workload level (Female: 40W and Male: 60W), safety (pain, VOC and acute chest syndrome), biological and echocardiography parameters, pulmonary function test (PFT), 6-minute walk test (6MWT), quality of life (QoL) and muscle properties and vascularization (biopsy of vastus lateralis muscle).
Results: Forty homozygous SCD patients (33±10 years, 23 male) were included. Four patients (3 EET and 1 control) were lost to follow-up. Data of 33 patients (15 EET and 18 controls) were analyzed. EET and control patients were comparable at baseline with regard to CPET, clinical, biological, and resting cardiorespiratory parameters. EET patients presented a significant increase of CPET workload at BL4 (p=0.031), BL2.5 (p=0.003) and LT1 (p&lt;0.0001) compared to the control group that remained unchanged. BL levels at a given level decreased significantly by 18% in the EET group compared to control group (p=0.01). Among the 40 randomized patients, 5 MAE occurred in the control group and 2 in the EET group. Quality of life improved for vitality (p=0.04) and physical activity (p=0.03) in the EET group compared to control group. Thigh biopsy showed in the EET group a significant increase of the proportion of oxidative type I fibers and of COX activity, paralleled by a significant increase in capillary density. No significant alterations were found in the control group. No change was found according to biological and echocardiography parameters, 6MWT and pulmonary function test.
Conclusion In SCD patients, EET based on Blood lactate guidance is safe and yields a significant functional benefit. This benefit is linked essentially to improved oxidative function of the peripheral skeletal musculature.

Disclosures
Galactéros: Addmedica: Membership on an entity's Board of Directors or advisory committees. Bartolucci: GBT: Membership on an entity's Board of Directors or advisory committees; Addmedica: Research Funding; Fondation Fabre: Research Funding; Novartis US: Membership on an entity's Board of Directors or advisory committees.