Sleep Apnea in Sickle Cell Disease

Sickle Cell Disease Clinical Trial

— DREPAPNEE  

Official title:

Effects of Obstructive Sleep Apnea on the Frequency of Vaso-occlusive Crises Events and Bio-physical Markers in Sickle Cell Disease

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03753854
• Other study ID #: 69HCL17_0784
• Secondary ID: 2017-A03352-51
• Status: Terminated
• Phase: N/A
• Start date: May 28, 2018
• Est. completion date: November 29, 2021

Study information

• Verified date: December 2022
• Source: Hospices Civils de Lyon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 30
• Est. completion date: November 29, 2021
• Est. primary completion date: November 29, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease
• Sleep Apnea Syndromes

Intervention

Diagnostic Test:
• polysomnography and oxygen saturation exam
Measurement of the Apnea/hypopnea index (AHI) and oxygen saturation

Biological:
• calculation 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
• Blood samples
Blood samples with measurements of hematological, hemorheological, inflammatory and blood coagulation markers

Other:
• Physiological measurements
Evaluation of microvascular reactivity and autonomic nervous system activity
• Continuous Positive Airway Pressure
Continuous Positive Airway Pressure during 1 year

Locations

Country	Name	City	State
France	Centre Léon Berard	Lyon
France	Hôpital de la Croix Rousse	Lyon
France	Hôpital Edouard Herriot	Lyon

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	number of VOC crises required hospitalization in the previous two years	Calculated over a 2 years period before inclusion. VOC requiring hospitalizations will be recorded.; Measured at day 1	day 1
Secondary	Blood inflammatory markers	Blood inflammatory markers : C Reactive Protein (CRP, mg/L) The morning after the polysomnography blood samples will be collected (M1 +/- 15 days)	An average of 1 month
Secondary	Blood inflammatory markers	Blood inflammatory markers : C Reactive Protein (CRP, mg/L)	Day 365
Secondary	Markers of blood coagulation	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)	An average of 1 month
Secondary	Markers of blood coagulation	prothrombin time (PT, s), D-dimer (µg/L), Fibrinogen (g/L), Activated Thromboplastin Time (APPT, s), protein C and protein S (%)	Day 365
Secondary	Blood cell counts and markers of hemolysis	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)	An average of 1 month
Secondary	Blood cell counts and markers of hemolysis	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).	Day 365
Secondary	Markers of nitric oxide metabolism	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)	An average of 1 month
Secondary	Markers of nitric oxide metabolism	markers of nitric oxide production nitrites, nitrate, nitrotyrosine	Day 365
Secondary	Oxidative stress markers	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)	An average of 1 month
Secondary	Oxidative stress markers	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)	Day 365
Secondary	Hemorheological parameters	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)	An average of 1 month
Secondary	Hemorheological parameters	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.	Day 365
Secondary	Arterial blood gases	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)	An average of 1 month
Secondary	Arterial blood gases	oxygen and carbon dioxide pressure (mmHg), pH	Day 365
Secondary	Vascular function (microvascular reactivity to skin heating test)	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.	Day 1
Secondary	Vascular function (microvascular reactivity to skin heating test)	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.	Day 365
Secondary	autonomic nervous system activity (measured by heart rate variability analysis)	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.	Day 1
Secondary	autonomic nervous system activity (measured by heart rate variability analysis)	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.	Day 365
Secondary	Frequency of VOC	Number of VOC requiring hospitalizations during the past year	Day 365