Sickle Cell Disease
Conditions
Keywords
sickle cell disease, obstructive sleep apnoea, vaso-occlusive crisis
Brief summary
Despite the fact that obstructive sleep apnoea (OSA) is highly prevalent in the sickle cell population, studies focusing on the associations of the two diseases and their common pathophysiological mechanisms are scarce. OSA is one of the most common conditions responsible for hemoglobin desaturation. The nocturnal hemoglobin desaturation occurring in some sickle cell disease (SCD) patients with OSA could trigger hemoglobin S polymerization and red blood cell (RBC) sickling, leading to further blood rheological alterations, hence increasing the risks for VOC. Moreover, OSA has been demonstrated to increase oxidative stress and inflammation in non Sickle Cell Disease (SCD) patients, which, in SCD patients, could increase the risk for complications. Finally, OSA is accompanied by impaired vascular function and autonomic nervous system dysfunction in the general population. Indeed, the presence of OSA in SCD could increase the clinical severity of patients and the frequency of VOC.
Interventions
DIAGNOSTIC_TESTpolysomnography and oxygen saturation exam
Measurement of the Apnea/hypopnea index (AHI) and oxygen saturation
BIOLOGICALcalculation of VOC frequency between the first polysomnography and the end of the first year of continuous positive airway pressure treatment
calculation of VOC rate within the two previous years or between first polysomnography and one year of continuous positive airway pressure treatment
BIOLOGICALBlood samples
Blood samples with measurements of hematological, hemorheological, inflammatory and blood coagulation markers
Evaluation of microvascular reactivity and autonomic nervous system activity
OTHERContinuous Positive Airway Pressure
Continuous Positive Airway Pressure during 1 year
Sponsors
Hospices Civils de Lyon
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
15 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Homozygous HbS (Hemoglobin S) (SS) patients, * aged between 15 and 3 months and 50 years old, * in steady state (i.e. without vaso-occlusive crisis or recent blood transfusion), * followed by the sickle cell center of the Hospices Civils de Lyon, * and showing symptoms of OSA.
Exclusion criteria
* Patients receiving treatment of OSA, * recent blood transfusion (less than 2 months), * patients not at steady state (VOC or acute chest syndrome less than 2 months), * pregnancy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| number of VOC crises required hospitalization in the previous two years | day 1 | Calculated over a 2 years period before inclusion. VOC requiring hospitalizations will be recorded. Measured at day 1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Markers of blood coagulation | An average of 1 month | Biological risk factors of VOC : prothrombin time (PT, s), D-dimer (µg/L), Fibrinogen (g/L), Activated Thromboplastin Time (APPT, s), protein C and protein S (%) The morning after the polysomnography blood samples will be collected (M1 +/- 15 days) |
| Blood cell counts and markers of hemolysis | An average of 1 month | Biological risk factors of VOC : Blood cell counts and markers of hemolysis : red blood cell count (G/L), neutrophil count (G/L), hemoglobin concentration (g/dL), hematocrit (%), mean corpuscular volume (MCV, fl), mean corpuscular hemoglobin concentration (MCHC, pg), platelet count (G/L), lactate dehydrogenase (LDH, IU), bilirubin (µg/L), aspartate transaminase (AST, U/L). The morning after the polysomnography blood samples will be collected (M1 +/- 15 days) |
| Markers of nitric oxide metabolism | An average of 1 month | Biological risk factors of VOC : markers of nitric oxide production nitrites, nitrate, nitrotyrosine The morning after the polysomnography blood samples will be collected (M1 +/- 15 days) |
| Oxidative stress markers | An average of 1 month | Biological risk factors of VOC : protein oxidation marker (advanced oxidation protein products), markers of lipid peroxidation (malondialdehyde), antioxidant enzymatic activities (super oxide dismutase, catalase, glutathione peroxidase), antioxidant power (ferric reducing ability of plasma) The morning after the polysomnography blood samples will be collected (M1 +/- 15 days) |
| Blood inflammatory markers | An average of 1 month | Blood inflammatory markers : C Reactive Protein (CRP, mg/L) The morning after the polysomnography blood samples will be collected (M1 +/- 15 days) |
| Arterial blood gases | An average of 1 month | Biological risk factors of VOC : oxygen and carbon dioxide pressure (mmHg), pH The morning after the polysomnography blood samples will be collected (M1 +/- 15 days) |
| Vascular function (microvascular reactivity to skin heating test) | Day 1 | Physiological risk factors of VOC : A laser Doppler flowmeter (Periflux 5000 Perimed) will be used to measure skin blood flow in resting condition and during a local thermal hyperemia (LTH) test (temperature will be increased from 33 °C to 42 °C) for 35 min. The peak response during the LTH reflects vasodilatation caused by axonal reflex while the delayed plateau response of the LTH test is mainly dependent on the ability to produce nitric oxide to promote vasodilation. |
| autonomic nervous system activity (measured by heart rate variability analysis) | Day 1 | Physiological risk factors of VOC : electrocardiographic signals acquired by the polysomnographic machine will be extracted and the R-R intervals will be used for time domain spectral analyses to calculate several indices reflecting the activity of the autonomic nervous system activity. The ratio between the low frequency and the high frequency powers (LF/HF) will be used to characterize the autonomic imbalance. |
| Frequency of VOC | Day 365 | Number of VOC requiring hospitalizations during the past year |
| Hemorheological parameters | An average of 1 month | blood viscosity (cP) measured with a cone plate viscometer at several shear rates, red blood cell deformability (a.u) measured by ektacytometry at several shear stresses, red blood cell aggregation (%) properties measured by laser backscatter method. The morning after the polysomnography blood samples will be collected (M1 +/- 15 days) |
Countries
France
Outcome results
None listed