Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 9 of 696 for:    Sickle Cell Disease

Sleep Apnea in Sickle Cell Disease (DREPAPNEE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03753854
Recruitment Status : Recruiting
First Posted : November 27, 2018
Last Update Posted : December 17, 2018
Sponsor:
Information provided by (Responsible Party):
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.

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

Layout table for study information
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
Active Comparator: SS patients

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
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

Experimental: SS patients apneic

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
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 :
  1. 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 :
  1. 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)

  2. Blood inflammatory markers [ Time Frame: Day 365 ]
    Blood inflammatory markers : C Reactive Protein (CRP, mg/L)

  3. 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)

  4. 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 (%)

  5. 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)


  6. 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).

  7. 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)

  8. Markers of nitric oxide metabolism [ Time Frame: Day 365 ]
    markers of nitric oxide production nitrites, nitrate, nitrotyrosine

  9. 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)

  10. 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)

  11. 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)


  12. 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.

  13. 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)

  14. Arterial blood gases [ Time Frame: Day 365 ]
    oxygen and carbon dioxide pressure (mmHg), pH

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Frequency of VOC [ Time Frame: Day 365 ]
    Number of VOC requiring hospitalizations during the past year



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
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
Layout table for location contacts
Contact: Emeric Stauffer, MD +33 4 26 10 92 67 emeric.stauffer@chu-lyon.fr

Locations
Layout table for location information
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

Layout table for additonal information
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

Layout table for additional information
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:
sickle cell disease
obstructive sleep apnoea
vaso-occlusive crisis
Additional relevant MeSH terms:
Layout table for MeSH terms
Anemia, Sickle Cell
Respiration Disorders
Respiratory Tract Diseases
Sleep Disorders, Intrinsic
Sleep Wake Disorders
Nervous System Diseases
Hematologic Diseases
Genetic Diseases, Inborn
Sleep Apnea Syndromes
Apnea
Dyssomnias
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hemoglobinopathies