Sleep Apnea in Sickle Cell Disease (DREPAPNEE)
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| ClinicalTrials.gov Identifier: NCT03753854 |
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Recruitment Status :
Recruiting
First Posted : November 27, 2018
Last Update Posted : December 17, 2018
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Sponsor:
Hospices Civils de Lyon
Information provided by (Responsible Party):
Hospices Civils de Lyon
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Sickle Cell Disease | 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 | Not Applicable |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 80 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Basic Science |
| Official Title: | Effects of Obstructive Sleep Apnea on the Frequency of Vaso-occlusive Crises Events and Bio-physical Markers in Sickle Cell Disease |
| Actual Study Start Date : | May 28, 2018 |
| Estimated Primary Completion Date : | October 28, 2021 |
| Estimated Study Completion Date : | October 28, 2021 |
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: SS patients
Homozygous sickle cell patients Each patient will undergo the following:
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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 Biological: 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 |
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Experimental: SS patients apneic
Homozygous sickle cell patients after one year of continuous positive airway pressure treatment Each patient will undergo the following:
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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 Biological: 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 Other: Continuous Positive Airway Pressure Continuous Positive Airway Pressure during 1 year |
Primary Outcome Measures :
- number of VOC crises required hospitalization in the previous two years [ Time Frame: day 1 ]
Calculated over a 2 years period before inclusion. VOC requiring hospitalizations will be recorded.
Measured at day 1
Secondary Outcome Measures :
- Blood inflammatory markers [ Time Frame: 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)
- Blood inflammatory markers [ Time Frame: Day 365 ]Blood inflammatory markers : C Reactive Protein (CRP, mg/L)
- Markers of blood coagulation [ Time Frame: 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)
- Markers of blood coagulation [ Time Frame: Day 365 ]prothrombin time (PT, s), D-dimer (µg/L), Fibrinogen (g/L), Activated Thromboplastin Time (APPT, s), protein C and protein S (%)
- Blood cell counts and markers of hemolysis [ Time Frame: 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)
- Blood cell counts and markers of hemolysis [ Time Frame: 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 [ Time Frame: 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)
- Markers of nitric oxide metabolism [ Time Frame: Day 365 ]markers of nitric oxide production nitrites, nitrate, nitrotyrosine
- Oxidative stress markers [ Time Frame: 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)
- Oxidative stress markers [ Time Frame: 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)
- Hemorheological parameters [ Time Frame: 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)
- Hemorheological parameters [ Time Frame: 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.
- Arterial blood gases [ Time Frame: 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)
- Arterial blood gases [ Time Frame: Day 365 ]oxygen and carbon dioxide pressure (mmHg), pH
- Vascular function (microvascular reactivity to skin heating test) [ Time Frame: 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.
- Vascular function (microvascular reactivity to skin heating test) [ Time Frame: 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.
- autonomic nervous system activity (measured by heart rate variability analysis) [ Time Frame: 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.
- autonomic nervous system activity (measured by heart rate variability analysis) [ Time Frame: 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.
- Frequency of VOC [ Time Frame: Day 365 ]Number of VOC requiring hospitalizations during the past year
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| Ages Eligible for Study: | 15 Years to 50 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03753854
Contacts
| Contact: Emeric Stauffer, MD | +33 4 26 10 92 67 | emeric.stauffer@chu-lyon.fr |
Locations
| France | |
| Hôpital Edouard Herriot | Recruiting |
| Lyon, France, 69003 | |
| Contact: Giovanna CANNAS 4.72.11.74.12 ext +33 giovanna.cannas@chu-lyon.fr | |
| Principal Investigator: Giovanna CANNAS | |
| Sub-Investigator: Solène POUTREL | |
| Centre Léon Berard | Recruiting |
| Lyon, France, 69008 | |
| Contact: Alexandra GAUTHIER 4.69.16.65.67 ext +33 alexandra.gauthier@ihope.fr | |
| Principal Investigator: Alexandra GAUTHIER | |
| Hôpital de la Croix Rousse | Recruiting |
| Lyon, France, 69317 | |
| Contact: Emeric STAUFFER, MD +33 4 26 10 92 67 emeric.stauffer@chu-lyon.fr | |
| Principal Investigator: Emeric Stauffer, MD | |
| Sub-Investigator: Thierry PETITJEAN, PH | |
Sponsors and Collaborators
Hospices Civils de Lyon
| Responsible Party: | Hospices Civils de Lyon |
| ClinicalTrials.gov Identifier: | NCT03753854 History of Changes |
| Other Study ID Numbers: |
69HCL17_0784 2017-A03352-51 ( Other Identifier: ANSM number ) |
| First Posted: | November 27, 2018 Key Record Dates |
| Last Update Posted: | December 17, 2018 |
| Last Verified: | December 2018 |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Hospices Civils de Lyon:
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sickle cell disease obstructive sleep apnoea vaso-occlusive crisis |
Additional relevant MeSH terms:
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Sleep Apnea Syndromes Anemia, Sickle Cell Apnea Respiration Disorders Respiratory Tract Diseases Sleep Disorders, Intrinsic Dyssomnias Sleep Wake Disorders |
Nervous System Diseases Anemia, Hemolytic, Congenital Anemia, Hemolytic Anemia Hematologic Diseases Hemoglobinopathies Genetic Diseases, Inborn |