Sickle Cell DiseaseDREPAPNEENCT03753854
Sleep Apnea in Sickle Cell Disease
A study testing polysomnography and oxygen saturation exam, calculation of VOC frequency between the first polysomnography and the end of the first year of continuous positive airway pressure treatment and Blood samples in people with Sickle Cell Disease, run by Hospices Civils de Lyon at 3 sites in France.
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. Read more about this study
- Who is it for?
- Ages 15 to 50 years
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- polysomnography and oxygen saturation exam, calculation of VOC frequency between the first polysomnography and the end of the first year of continuous positive airway pressure treatment and Blood samples
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 3 sitesFrance
- Study dates
- 28 May 2018to 29 Nov 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 to 50 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
3 sites in 1 country.
France3 sites
Hôpital Edouard Herriot
Lyon, 69003
Centre Léon Berard
Lyon, 69008
Hôpital de la Croix Rousse
Lyon, 69317
About this study
Official title: 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.
- Conditions
- Sickle Cell Disease
- Being tested
- polysomnography and oxygen saturation exam, calculation of VOC frequency between the first polysomnography and the end of the first year of continuous positive airway pressure treatment, Blood samples, Physiological measurements, Continuous Positive Airway Pressure
- Keywords
- sickle cell disease, obstructive sleep apnoea, vaso-occlusive crisis
- Medical subject headings
- Anemia, Sickle Cell, Sleep Apnea, Obstructive, Vaso-Occlusive Crises
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
polysomnography and oxygen saturation examDiagnostic test
Measurement of the Apnea/hypopnea index (AHI) and oxygen saturation
calculation of VOC frequency between the first polysomnography and the end of the first year of continuous positive airway pressure treatmentBiological
calculation of VOC rate within the two previous years or between first polysomnography and one year of continuous positive airway pressure treatment
Blood samplesBiological
Blood samples with measurements of hematological, hemorheological, inflammatory and blood coagulation markers
Physiological measurementsOther
Evaluation of microvascular reactivity and autonomic nervous system activity
Continuous Positive Airway PressureOther
Continuous Positive Airway Pressure during 1 year
| Study group | Role | What they receive |
|---|---|---|
| SS patients | Active comparator | 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 Receives: 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 |
| SS patients apneic | Experimental | 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 Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: day 1
Secondary outcomes (19)
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)
Measured: An average of 1 month
Blood inflammatory markers
Blood inflammatory markers : C Reactive Protein (CRP, mg/L)
Measured: Day 365
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)
Measured: An average of 1 month
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 (%)
Measured: Day 365
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)
Measured: An average of 1 month
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).
Measured: Day 365
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)
Measured: An average of 1 month
Markers of nitric oxide metabolism
markers of nitric oxide production nitrites, nitrate, nitrotyrosine
Measured: Day 365
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)
Measured: An average of 1 month
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)
Measured: Day 365
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)
Measured: An average of 1 month
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.
Measured: Day 365
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)
Measured: An average of 1 month
Arterial blood gases
oxygen and carbon dioxide pressure (mmHg), pH
Measured: Day 365
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.
Measured: Day 1
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.
Measured: Day 365
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.
Measured: Day 1
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.
Measured: Day 365
Frequency of VOC
Number of VOC requiring hospitalizations during the past year
Measured: Day 365
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Nov 2018
- Study start28 May 2018
- Primary completion29 Nov 2021
- Study completion29 Nov 2021
Why it stopped: Recruitment difficulties
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03753854
- Sponsor's protocol ID
- 69HCL17_0784
- Other IDs
- 2017-A03352-51
- Acronym
- DREPAPNEE
- Status last verified
- Dec 2022
- First submitted
- 20 Nov 2018
- Last updated
- 28 Dec 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Stauffer E, Poutrel S, Cannas G, Gauthier A, Fort R, Bertrand Y, Renoux C, Joly P, Boisson C, Hot A, Peter-Derex L, Pialoux V, PetitJean T, Connes P. Nocturnal Hypoxemia Rather Than Obstructive Sleep Apnea Is Associated With Decreased Red Blood Cell Deformability and Enhanced Hemolysis in Patients With Sickle Cell Disease. Front Physiol. 2021 Sep 24;12:743399. doi: 10.3389/fphys.2021.743399. eCollection 2021.
PubMed 34630163
Study at a glance
From the registry record, last updated by the sponsor on 28 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Obstructive Sleep Apnea on the Frequency of Vaso-occlusive Crises Events and Bio-physical Markers in Sickle Cell Disease
- ClinicalTrials.gov ID
- NCT03753854
- Acronym / sponsor ID
- DREPAPNEE / 69HCL17_0784
- Conditions
- Sickle Cell Disease
- Keywords
- sickle cell disease, obstructive sleep apnoea, vaso-occlusive crisis
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Recruitment difficulties
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- 28 May 2018 (actual)
- Primary completion
- 29 Nov 2021 (actual)
- Study completion
- 29 Nov 2021 (actual)
- First posted
- 27 Nov 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SS patients | Active comparator | 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 measurementsHomozygous 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 | Experimental | 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 PressureHomozygous 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 |
Who may qualify
- Ages
- 15 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| polysomnography and oxygen saturation examMeasurement of the Apnea/hypopnea index (AHI) and oxygen saturation | Diagnostic test | SS patients, SS patients apneic |
| calculation of VOC frequency between the first polysomnography and the end of the first year of continuous positive airway pressure treatmentcalculation of VOC rate within the two previous years or between first polysomnography and one year of continuous positive airway pressure treatment | Biological | SS patients, SS patients apneic |
| Blood samplesBlood samples with measurements of hematological, hemorheological, inflammatory and blood coagulation markers | Biological | SS patients, SS patients apneic |
| Physiological measurementsEvaluation of microvascular reactivity and autonomic nervous system activity | Other | SS patients, SS patients apneic |
| Continuous Positive Airway PressureContinuous Positive Airway Pressure during 1 year | Other | SS patients apneic |
Primary outcome
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
19 secondary outcomes
Blood inflammatory markers
Time frame: An average of 1 month
Blood inflammatory markers
Time frame: Day 365
Markers of blood coagulation
Time frame: An average of 1 month
Markers of blood coagulation
Time frame: Day 365
Blood cell counts and markers of hemolysis
Time frame: An average of 1 month
Blood cell counts and markers of hemolysis
Time frame: Day 365
Markers of nitric oxide metabolism
Time frame: An average of 1 month
Markers of nitric oxide metabolism
Time frame: Day 365
Oxidative stress markers
Time frame: An average of 1 month
Oxidative stress markers
Time frame: Day 365
Hemorheological parameters
Time frame: An average of 1 month
Hemorheological parameters
Time frame: Day 365
Arterial blood gases
Time frame: An average of 1 month
Arterial blood gases
Time frame: Day 365
Vascular function (microvascular reactivity to skin heating test)
Time frame: Day 1
Vascular function (microvascular reactivity to skin heating test)
Time frame: Day 365
autonomic nervous system activity (measured by heart rate variability analysis)
Time frame: Day 1
autonomic nervous system activity (measured by heart rate variability analysis)
Time frame: Day 365
Frequency of VOC
Time frame: Day 365
Results and safety
The study was stopped early (reason given: Recruitment difficulties). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Dec 2022.
- Derived from this study: PubMed 34630163Stauffer E, Poutrel S, Cannas G, Gauthier A, Fort R, Bertrand Y, Renoux C, Joly P, Boisson C, Hot A, Peter-Derex L, Pialoux V, PetitJean T, Connes P. Nocturnal Hypoxemia Rather Than Obstructive Sleep Apnea Is Associated With Decreased Red Blood Cell Deformability and Enhanced Hemolysis in Patients With Sickle Cell Disease. Front Physiol. 2021 Sep 24;12:743399. doi: 10.3389/fphys.2021.743399. eCollection 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing polysomnography and oxygen saturation exam, calculation of VOC frequency between the first polysomnography and the end of the first year of continuous positive airway pressure treatment and Blood samples in people with Sickle Cell Disease, run by Hospices Civils de Lyon at 3 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Recruitment difficulties). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
number of VOC crises required hospitalization in the previous two years (time frame: day 1). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03753854, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Dec 2022.