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Apnea, Stroke and Incident Cardiovascular Events (ASCENT)

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ClinicalTrials.gov Identifier: NCT04399200
Recruitment Status : Not yet recruiting
First Posted : May 22, 2020
Last Update Posted : May 22, 2020
Sponsor:
Information provided by (Responsible Party):
University Hospital, Grenoble

Brief Summary:

This prospective cohort study aims to compare the proportion of cardiac or cerebrovascular events after a first stroke, a first transient ischemic attack (TIA) or recurrent TIA, between sleep-disordered breathing (SDB) and non-SDB (control) patients, one year after SDB diagnosis, performed 3 months after stroke onset.

The primary outcome is a composite endpoint composed of cardiac or cerebrovascular events regrouping: death from any cardiac or cerebrovascular cause, non-fatal stroke, and non-fatal acute coronary disease.

1620 patients, in the acute phase of a first stroke, TIA or recurrent TIA will be included in the cohort.

Clinical, neuroimaging, sensorimotor, cognitive and biological parameters will be collected at inclusion. Three months after stroke or TIA onset, polysomnography will be performed for SDB diagnosis. Patients will be considered as having SDB for an Apnea-Hypopnea Index (AHI) > 15 events/hour, or to the control group otherwise. The same clinical, imaging, cognitive and biological assessments than during the first visit will be performed; incident (new) cardiovascular events will be collected. Three months later, and at 1, 2, 3, 4 and 5 years after SDB diagnosis, the same clinical, cognitive, sensorimotor, and sleep-related evaluations will be performed. In addition to the aforementioned parameters, incident cardiovascular outcomes will be collected, at the same time points. The primary study outcome will be retrieved one year after stroke onset.


Condition or disease Intervention/treatment
Stroke Sleep-disordered Breathing Sleep Apnea Syndromes Sleep Apnea, Obstructive Sleep Apnea, Central Fragmentation, Sleep Device: Treatment according to standard care recommandation

Detailed Description:

This is a prospective cohort study that aims at comparing the proportion of incident cardiovascular events after a first stroke, first transient ischemic attack (TIA) or recurrent TIA, between sleep-disordered breathing patients (SDB, defined as an apnea-hypopnea index > 15 events/hour) and non-SDB patients, one year after SDB diagnosis performed by polysomnography 3 months after the cerebrovascular event.

The primary outcome is a composite endpoint composed of cardiac or cerebrovascular events (Major Adverse Cardiovascular Events, MACCEs), regrouping: death from any cardiac or cerebrovascular cause, non-fatal stroke, non-fatal acute coronary event. Secondary outcomes include secondary cardiac and cerebrovascular events; stroke-related functional criteria; lesion-related criteria obtained from morphological MRI; scores on questionnaires assessing the quality of life, depression and sleep; functional, cognitive and sensorimotor evaluations; locomotion tests; and sleep-related criteria.

1620 patients, aged 18 to 85 years, in the acute phase (<72h) of a first stroke, first or recurrent TIA, and with a score on the modified Rankin Scale (mRS) ≤1 before stroke onset, will be included in the cohort. All patients included in the study will be followed for 5 years. The schedule of follow-up will be as follow :

  • Selection visit (Days 0 to 3): verification of eligibility criteria, patients' or relatives' information, informed consent signature.
  • Inclusion visit (Days 4 to 7): clinical history and treatments, clinical evaluation and anthropometrical parameters, stroke-related criteria (including score on the National Institute of Health Stroke Scale), functional, cognitive, and sensorimotor evaluation, walking and locomotion tests, questionnaires, stroke imagery by magnetic resonance imagery, blood sampling.
  • SDB diagnosis (Month 3): the same clinical, MRI and biological parameters will be collected and the same questionnaires will be fulfilled by the patients. In addition, they will undergo polysomnography to assess their SDB status. Patients will be assigned to the SDB group if the AHI > 15 events/hour; otherwise they will be assigned to the control group. Patients assigned to the SDB group will be proposed a treatment for their SDB according to standard care procedures.
  • Clinical follow-up: sleep and neurological; (initial 3 months and then annually after SDB diagnosis up to 5 years after SDB diagnosis): retrieval of new cardiac or cerebrovascular events (primary study outcome (MACCEs)), stroke-related parameters, questionnaires, functional, cognitive, and sensorimotor evaluations, locomotion tests, sleep follow-up (adherence to SDB treatment, tolerance, efficacy). Biological sampling will also be done at 1, 2 and 5 years after SDB diagnosis.

Ancillary study - CAtSS (Carotid, Atherosclerosis, Stroke and Sleep apnea) Conjointly to the previously described ASCENT protocol, an ancillary study will be proposed to the subgroup of patients eligible for carotid surgery (endarterectomy) following their cerebrovascular event.

The purpose of this ancillary study is to evaluate the impact of SDB and SDB treatment on the evolution of the carotid plaque after surgery. For the patients who accepted to participate to this ancillary study, the degree of carotid stenosis and the artery wall thickness (intima-media thickness, assessed by echo-Doppler) will be measured during the inclusion visit, at 3 months, 6 months, and at each annual visit. During surgery, a fragment of carotid plaque will be kept for morphologic and histologic analyses as well as miRNAs dosing, miARNs being recognized as indicators of carotid plaque instability. Plasmatic and urine samples will also be collected for miRNA analyses.

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Study Type : Observational
Estimated Enrollment : 1620 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Sleep Apnea Syndrome and Incidence of Major Adverse Cardiac and Cerebrovascular Events (MACCEs) After a First Stroke
Estimated Study Start Date : June 1, 2020
Estimated Primary Completion Date : June 1, 2030
Estimated Study Completion Date : June 1, 2035

Group/Cohort Intervention/treatment
Sleep-disordered breathing group
Sleep-disordered breathing (SDB) patients (AHI>15/h, measured by polysomnography performed 3 months after stroke)
Device: Treatment according to standard care recommandation
SDB treatment according to standard care recommandation: Continuous Positive Airway Pressure (CPAP), Mandibular Advancement Device, Positionnal Therapy, Adaptive Servo-Ventilation (ASV), Non-Invasive Ventilation (NIV)

Control group
Control patients with no SDB (AHI<15/h, measured by polysomnography performed 3 months after stroke)



Primary Outcome Measures :
  1. Prevalence of Major Adverse Cardiac or Cerebrovascular Events (MACCEs) [ Time Frame: 1 year after SDB diagnosis ]
    Composite endpoint composed of cardiac or cerebrovascular events regrouping: death from cardiac of cerebrovascular cause, non fatal stroke (either ischemic or hemorrhagic), and non-fatal acute coronary disease


Secondary Outcome Measures :
  1. Prevalence of Major Adverse Cardiac or Cerebrovascular Events (MACCEs) [ Time Frame: 5 years after SDB diagnosis ]
    Composite endpoint composed of cardiac or cerebrovascular events regrouping: death from cardiac of cerebrovascular cause, non fatal stroke (either ischemic or hemorrhagic), and non-fatal acute coronary disease

  2. Prevalence of secondary cardiac or cerebrovascular events [ Time Frame: 5 years after SDB diagnosis ]
    Composite endpoint composed of cardiac or cerebrovascular events regrouping: transient ischemic attack (TIA), any acute coronary disease, hospitalization for any cardio-vascular cause and peripheral artery disease

  3. Change in BMI from inclusion to 5 years [ Time Frame: at inclusion, and at each visit up to 5 years after SDB diagnosis ]
    Change in body mass index (BMI), defined as weight (Kg)/height (m)². This will be calculated at inclusion and at each visit

  4. Change in waist, neck, and abdominal circumferences, from inclusion visit to 5 years [ Time Frame: at inclusion, and at each visit up to 5 years after SDB diagnosis ]
    Change in waist, neck and abdominal circumferences in cm. This will be measured at inclusion and at each visit.

  5. Change in NIHSS score from inclusion to 5 years [ Time Frame: at inclusion, and at each visit up to 5 years after SDB diagnosis ]
    Stroke severity assessed by National Institute of Health Stroke Scale (NIHSS). This tool is composed of 15 items, each assessing specific abilities. (0: no stroke symptoms; 1 to 4: minor stroke; 5 to 15: moderate stroke; 16-20: moderate to severe stroke; >20 : severe stroke). The scale will be administered at each visit.

  6. ABCD² score at inclusion [ Time Frame: at inclusion ]
    Score evaluating the risk for stroke after a transient ischemic attack (TIA). The scale ranges from 0 (low level) to 7 (high level). 0 to 3: low risk; 4 to 5: moderate, 6 to 7: high risk

  7. Clinical outcome: change in modified Ranking Sale (mRS) from inclusion to 5 years [ Time Frame: at inclusion, and at each visit up to 5 years after SDB diagnosis ]
    Scale assessing functional outcome after stroke, ranging from 0 (no symptoms at all) to 5 (severe disability), measured at each visit

  8. Clinical outcome: change in Functional Independence Measure (FIM) from inclusion to 5 years [ Time Frame: at inclusion, and at each visit up to 5 years after SDB diagnosis ]
    Scale assessing functional outcome after stroke, ranging from 18 (totally dependent) to 126 (totally independent), measured at each visit

  9. Clinical outcome: change in Stroke Impact Scale (SIS-16) from inclusion to 5 years [ Time Frame: at inclusion, and at each visit up to 5 years after SDB diagnosis ]
    This scale assess patient's health after stroke, through 16 items evaluating functional independence and mobility. This scale ranges from 16 (total independance) to 80 (total dependancy). The scale will be administer at each visit

  10. Clinical outcome: change Patient Health Questionnaire (PHQ-9) from inclusion to 5 years [ Time Frame: at inclusion, and at each visit up to 5 years after SDB diagnosis ]
    Scale assessing patient's depression symptoms, administered at each visit. The scale ranges from 0 (no depression) to 27 (severe depression).

  11. Clinical outcome: change Fugl-Meyer Assessment Scale from inclusion to 5 years [ Time Frame: at inclusion, and at each visit up to 5 years after SDB diagnosis ]
    Scale assessing sensori-motor upper extremity function in post-stroke patients, administered at each visit. The maximal possible score is 226, which corresponds to a complete sensori-motor recovery.

  12. Change in walking and locomotion abilities: nFAC score, from inclusion to 5 years [ Time Frame: at inclusion, and at each visit up to 5 years after SDB diagnosis ]
    Evaluation of ambulation abilities, from 0 (cannot walk) to 8 (able to walk independantly)

  13. Change in walking and locomotion abilities: 10m walking test, from inclusion to 5 years [ Time Frame: at inclusion, and at each visit up to 5 years after SDB diagnosis ]
    Evaluation of speed on the 10m walking test

  14. Change in daytime sleepiness: score on the Epworth Sleepiness Scale, from inclusion to 5 years [ Time Frame: at inclusion, and at each visit up to 5 years after SDB diagnosis ]
    Daytime sleepiness score measured by Epworth Sleepiness Scale. The scale ranges from 0 (no sleepiness) to 24 (severe sleepiness)

  15. Change in daytime sleepiness: score Berlin Questionnaire for Sleep Apnea (BQSA) [ Time Frame: at inclusion, and at each visit up to 5 years after SDB diagnosis ]
    Sleep apnea screening questionnaire that identifies the risk (from low to high) of sleep disordered breathing

  16. Assessment of sleep and fatigue: score change on Chalder Fatigue Scale from inclusion to 5 years [ Time Frame: at inclusion, and at each visit up to 5 years after SDB diagnosis ]
    Questionnaire evaluating the severity of tiredness, on a scale ranging from 0 (no fatigue) to 33 (severe), administered at each visit

  17. Assessment of sleep and fatigue: score change on Fatigue Severity Scale (FSS) from inclusion to 5 years [ Time Frame: at inclusion, and at each visit up to 5 years after SDB diagnosis ]
    Questionnaire evaluating the severity of tiredness, on a scale ranging from 9 (no fatigue) to 63 (severe), administered at each visit

  18. Assessment of sleep and fatigue: score change on Pichot's Fatigue Scale from inclusion to 5 years [ Time Frame: at inclusion, and at each visit up to 5 years after SDB diagnosis ]
    Questionnaire evaluating the severity of tiredness, on a scale ranging from 0 (no fatigue) to 32 (severe), administered at each visit

  19. Change in depression symptoms from inclusion to 5 years : Pichot's Depression Scale (QD2A) [ Time Frame: at inclusion, and at each visit up to 5 years after SDB diagnosis ]
    Questionnaire evaluating depression symptoms through right/false responses to 13 items, administered at each visit (score: 0 to 13)

  20. Change in cognitive abilities from inclusion to 5 years: scores on the Montreal Cognitive Assessment Test [ Time Frame: at inclusion, and at each visit up to 5 years after SDB diagnosis ]
    Global assessment of cognitive functions, evaluating on 30 points and in 10 minutes short-term memory, verbal fluency, visuoconstructive abilities, executive functions, attention, working memory, language and spatiotemporal orientation. The test will be administered at each visit.

  21. Change in cognitive abilities from inclusion to 5 years : scores on the Frontal Assessment Battery [ Time Frame: at inclusion, and at each visit up to 5 years after SDB diagnosis ]
    Short screening test evaluating executive function, on a scale from 0 (severe disability) to 18 (no disability)

  22. Change in cognitive abilities from inclusion to 5 years : Language Screening Test (LAST) [ Time Frame: at inclusion, and at each visit up to 5 years after SDB diagnosis ]
    Rapid evaluation of language abilities (oral expression and comprehension) through 15 items (total score: 15).

  23. Prevalence of SDB assessed by polysomnography [ Time Frame: 3 months post-stroke ]
    Prevalence of SDB, assessed by polysomnography, and defined as AHI (Apnea-Hypopnea Index >15/h)

  24. Prevalence of respiratory disorders [ Time Frame: 3 months post-stroke ]
    Respiratory assessments : spirometry, plethysmography, CO diffusion, blood gas measurement, measurement of ventilatory response to CO2

  25. Change in adherence to SDB treatments, from 6 months to 5 years after SDB diagnosis [ Time Frame: from 6 months and at each visit up to 5 years after SDB diagnosis ]
    Treatment adherence, assessed by CPAP monitoring (mean hours/night) if applicable

  26. Stroke characteristics : lesion volume [ Time Frame: At inclusion ]
    Stroke volume in mm3, determined on MRI/CT scan

  27. Concentration of C-Reactive protein [ Time Frame: 3 months ]
    Concentration of C-Reactive protein by blood sampling

  28. Change in degree of carotid stenosis (ancillary study) [ Time Frame: from 3 months to 5 years after SDB diagnosis ]
    NASCET (North American Symptomatic Carotid Endarterectomy) evaluation of carotid stenosis in percent by Echo-doppler

  29. Change in intima-media thickness (ancillary study) from 3 months to 5 years [ Time Frame: from 3 months to 5 years after SDB diagnosis ]
    Measurement of carotid intima-media thickness (in mm) by Echo-Doppler

  30. Plasmatic and urinary miRNAs (ancillary study) [ Time Frame: from 3 months to 5 years after SDB diagnosis ]
    miRNA expression and modulation in plasma and urine

  31. miRNAs in carotid artery plaque (ancillary study) [ Time Frame: At baseline (carotid surgery) ]
    miARNs expression and modulation in carotid artery plaque

  32. Prevalence of post-operative complication (ancillary study) [ Time Frame: from 3 months to 5 years after SDB diagnosis ]
    Prevalence of post-operative complication defined as post-operative hematomy, nerve palsy of nerves X and XII, per - post-operative ischemic or hemorragic strokes, myocardial infarction, death

  33. Adipose tissue analysis (ancillary study) [ Time Frame: At baseline (carotid surgery) ]
    Morphological analysis of adipose tissue collected during endarteriectomy, expression of membrane and lipidic and glycemic markers, expression of inflammatory markers


Biospecimen Retention:   Samples With DNA
Blood Urine Carotid plaque


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.


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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients in the acute phase (<72h) of a first stroke or initial/recurrent TIA, admitted in the stroke unit of the Grenoble Alpes University Hospital.
Criteria

Inclusion Criteria:

  • Male or female, aged 18 to 85 years
  • Admitted in the stroke unit no later than 72h after the onset of stroke symptoms:

    • First stroke confirmed by computed tomography scan or magnetic resonance imaging, whatever the localization
    • Initial or recurrent TIA, as defined by a brief and sudden neurological dysfunction for which an ischemic cause is presumed, with symptoms lasting less than 24 hours, and/or with no visible lesion on neuroimaging evaluation.
  • Score on the Modified Ranking scale (mRS) ≤1 before stroke
  • Signed informed consent by patient or his/her relative if not able
  • Patient eligible to carotid endarterectomy (for ancillary study only)

Exclusion Criteria:

  • Pregnant or breastfeeding women
  • Past history of stroke
  • Inability to follow rehabilitation procedure
  • Patients with ongoing treatment for SDB
  • Exclusion period for another study
  • Patients not affiliated to a French social and health insurance system or equivalent
  • Prisoners or patients who require protection by the law

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): NCT04399200


Contacts
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Contact: Sébastien Baillieul, MD, MSc +33 (0)4 76 76 87 66 sbaillieul@chu-grenoble.fr
Contact: Marjorie Dole, PhD +33 (0)4 76 76 69 18 mdole2@chu-grenoble.fr

Locations
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France
University Hospital Grenoble
Grenoble, France, 38043
Contact: Sébastien Baillieul, MD, MSc    +33 (0)4 76 76 87 66    sbaillieul@chu-grenoble.fr   
Contact: Marjorie Dole, PhD    +33 (0)4 76 76 69 18    mdole2@chu-grenoble.fr   
Sub-Investigator: Jean-Louis Pépin, Pr         
Sub-Investigator: Marie Destors, MD         
Sub-Investigator: Chrystel Saint Raymond, MD         
Sub-Investigator: Olivier Detante, Pr         
Sub-Investigator: Isabelle Favre-Wiki, MD         
Sub-Investigator: Katia Garambois, MD         
Sub-Investigator: Raphaëlle Spear, MD         
Sponsors and Collaborators
University Hospital, Grenoble
Investigators
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Principal Investigator: Renaud Tamisier, MD, PhD, MBA University Hospital, Grenoble
Publications:
Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, de Ferranti SD, Floyd J, Fornage M, Gillespie C, Isasi CR, Jiménez MC, Jordan LC, Judd SE, Lackland D, Lichtman JH, Lisabeth L, Liu S, Longenecker CT, Mackey RH, Matsushita K, Mozaffarian D, Mussolino ME, Nasir K, Neumar RW, Palaniappan L, Pandey DK, Thiagarajan RR, Reeves MJ, Ritchey M, Rodriguez CJ, Roth GA, Rosamond WD, Sasson C, Towfighi A, Tsao CW, Turner MB, Virani SS, Voeks JH, Willey JZ, Wilkins JT, Wu JH, Alger HM, Wong SS, Muntner P; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2017 Update: A Report From the American Heart Association. Circulation. 2017 Mar 7;135(10):e146-e603. doi: 10.1161/CIR.0000000000000485. Epub 2017 Jan 25. Review. Erratum in: Circulation. 2017 Mar 7;135(10 ):e646. Circulation. 2017 Sep 5;136(10 ):e196.

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Responsible Party: University Hospital, Grenoble
ClinicalTrials.gov Identifier: NCT04399200    
Other Study ID Numbers: 2019-A03085-52
2019-A03085-52 ( Registry Identifier: CPP Sud-Méditerranée II )
First Posted: May 22, 2020    Key Record Dates
Last Update Posted: May 22, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Grenoble:
Stroke
Sleep-disordered Breathing
Cardio-Vascular Events
Atherosclerosis
Additional relevant MeSH terms:
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Apnea
Sleep Apnea Syndromes
Respiratory Aspiration
Sleep Apnea, Obstructive
Sleep Apnea, Central
Stroke
Sleep Deprivation
Syndrome
Disease
Pathologic Processes
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Neurologic Manifestations
Mental Disorders