Sleep Apnea in Sickle Cell Disease

Not Applicable

Terminated

• Conditions: Sickle Cell Disease
• Interventions: Diagnostic Test: polysomnography and oxygen saturation exam; Biological: calculation of VOC frequency between the first polysomnography and the end of the first year of continuous positive airway pressure treatment; Biological: Blood samples; Other: Physiological measurements; Other: Continuous Positive Airway Pressure

• Registration Number: NCT03753854
• Lead Sponsor: Hospices Civils de Lyon

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2018-05-28
• Study First Submitted: 2018-11-20
• Study First Submitted QC: 2018-11-23
• Study First Posted: 2018-11-27
• Primary Completion: 2021-11-29
• Study Completion: 2021-11-29
• Status Verified: 2022-12
• Last Update Submitted: 2022-12-23
• Last Update Posted: 2022-12-28

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 30

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SS patients	Physiological measurements	Homozygous sickle cell patients Each patient will undergo the following: 1. polysomnography and oxygen saturation exam 2. calculation of VOC rate within the two previous years 3. Blood samples 4. Physiological measurements
SS patients	polysomnography and oxygen saturation exam	Homozygous sickle cell patients Each patient will undergo the following: 1. polysomnography and oxygen saturation exam 2. calculation of VOC rate within the two previous years 3. Blood samples 4. Physiological measurements
SS patients	calculation of VOC frequency between the first polysomnography and the end of the first year of continuous positive airway pressure treatment	Homozygous sickle cell patients Each patient will undergo the following: 1. polysomnography and oxygen saturation exam 2. calculation of VOC rate within the two previous years 3. Blood samples 4. Physiological measurements
SS patients apneic	polysomnography and oxygen saturation exam	Homozygous sickle cell patients after one year of continuous positive airway pressure treatment Each patient will undergo the following: 1. polysomnography and oxygen saturation exam 2. calculation of VOC rate within the two previous years 3. Blood samples 4. Physiological measurements
SS patients	Blood samples	Homozygous sickle cell patients Each patient will undergo the following: 1. polysomnography and oxygen saturation exam 2. calculation of VOC rate within the two previous years 3. Blood samples 4. Physiological measurements
SS patients apneic	Blood samples	Homozygous sickle cell patients after one year of continuous positive airway pressure treatment Each patient will undergo the following: 1. polysomnography and oxygen saturation exam 2. calculation of VOC rate within the two previous years 3. Blood samples 4. Physiological measurements
SS patients apneic	calculation of VOC frequency between the first polysomnography and the end of the first year of continuous positive airway pressure treatment	Homozygous sickle cell patients after one year of continuous positive airway pressure treatment Each patient will undergo the following: 1. polysomnography and oxygen saturation exam 2. calculation of VOC rate within the two previous years 3. Blood samples 4. Physiological measurements
SS patients apneic	Physiological measurements	Homozygous sickle cell patients after one year of continuous positive airway pressure treatment Each patient will undergo the following: 1. polysomnography and oxygen saturation exam 2. calculation of VOC rate within the two previous years 3. Blood samples 4. Physiological measurements
SS patients apneic	Continuous Positive Airway Pressure	Homozygous sickle cell patients after one year of continuous positive airway pressure treatment Each patient will undergo the following: 1. polysomnography and oxygen saturation exam 2. calculation of VOC rate within the two previous years 3. Blood samples 4. Physiological measurements

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Markers of blood coagulation	Day 365	prothrombin time (PT, s), D-dimer (µg/L), Fibrinogen (g/L), Activated Thromboplastin Time (APPT, s), protein C and protein S (%)
Vascular function (microvascular reactivity to skin heating test)	Day 365	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.
Blood inflammatory markers	Day 365	Blood inflammatory markers : C Reactive Protein (CRP, mg/L)
Blood cell counts and markers of hemolysis	Day 365	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).
Markers of nitric oxide metabolism	Day 365	markers of nitric oxide production nitrites, nitrate, nitrotyrosine
Hemorheological parameters	Day 365	Biological risk factors of VOC : 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.
Frequency of VOC	Day 365	Number of VOC requiring hospitalizations during the past year
Oxidative stress markers	Day 365	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)
Arterial blood gases	Day 365	oxygen and carbon dioxide pressure (mmHg), pH
autonomic nervous system activity (measured by heart rate variability analysis)	Day 365	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.

Trial Locations

Locations (3)

Hôpital Edouard Herriot; 🇫🇷 Lyon, France

Centre Léon Berard; 🇫🇷 Lyon, France

Hôpital de la Croix Rousse; 🇫🇷 Lyon, France