Sleep Apnea in Sickle Cell Disease (DREPAPNEE)

December 23, 2022 updated by: Hospices Civils de Lyon

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Lyon, France, 69008
        • Centre Leon Bérard
      • Lyon, France, 69003
        • Hôpital Edouard Herriot
      • Lyon, France, 69317
        • Hopital de la Croix Rousse

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

15 years to 50 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
day 1

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
An average of 1 month
Blood inflammatory markers
Time Frame: Day 365
Blood inflammatory markers : C Reactive Protein (CRP, mg/L)
Day 365
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)
An average of 1 month
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 (%)
Day 365
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)
An average of 1 month
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).
Day 365
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)
An average of 1 month
Markers of nitric oxide metabolism
Time Frame: Day 365
markers of nitric oxide production nitrites, nitrate, nitrotyrosine
Day 365
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)
An average of 1 month
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)
Day 365
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)
An average of 1 month
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.
Day 365
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)
An average of 1 month
Arterial blood gases
Time Frame: Day 365
oxygen and carbon dioxide pressure (mmHg), pH
Day 365
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.
Day 1
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.
Day 365
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.
Day 1
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.
Day 365
Frequency of VOC
Time Frame: Day 365
Number of VOC requiring hospitalizations during the past year
Day 365

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospices Civils de Lyon

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 28, 2018

Primary Completion (Actual)

November 29, 2021

Study Completion (Actual)

November 29, 2021

Study Registration Dates

First Submitted

November 20, 2018

First Submitted That Met QC Criteria

November 23, 2018

First Posted (Actual)

November 27, 2018

Study Record Updates

Last Update Posted (Actual)

December 28, 2022

Last Update Submitted That Met QC Criteria

December 23, 2022

Last Verified

December 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 69HCL17_0784
  • 2017-A03352-51 (Other Identifier: ANSM number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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