The Effects of CPAP Withdrawal on Cerebral Vascular Reactivity and Brain Oxygenation in OSA

NCT02493673 | Completed

• 1 other identifier: KEK-ZH-Nr. 2014-0684
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief Summary

Obstructive sleep apnoea (OSA) is a highly prevalent sleep-related breathing disorder associated with adverse cardiovascular outcome. Underlying mechanisms are subject of debate. A causal relationship between OSA and systemic hypertension as well as peripheral endothelial dysfunction was shown, and there is accumulating evidence from physiologic and observational studies that cerebral autoregulation is insufficient to protect the brain from the nocturnal consequences of OSA. However, there are no data from randomised controlled trials proving a causal relationship between OSA and impaired cerebral vascular reactivity (CVR). The aim of this randomised controlled trial is to study the effects of a short-term CPAP withdrawal, and thus returning OSA, on daytime CVR and brain oxygenation to establish whether there is a causal relationship between OSA and cerebral vascular damage.

Conditions

Sleep Apnea, Obstructive

Keywords

Continuous Positive Airway Pressure; Stroke; Cerebrovascular reactivity; Brain oxygenation

Outcome Measures

Primary Outcomes (1)

• Cerebrovascular reactivity (CVR)

  CVR measured non-invasively by blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) under controlled cardiovascular reactivity stimulation during wakefulness

  Change from baseline in CVR after 2 weeks of CPAP withdrawal

Secondary Outcomes (4)

• Ambulatory morning blood pressure

  Change from baseline in ambulatory morning blood pressure after 2 weeks of CPAP withdrawal

• Resting heart rate

  Change from baseline in resting heart rate after 2 weeks of CPAP withdrawal

• Apnoea-hypopnoea-index (AHI)

  Change from baseline in AHI after 2 weeks of CPAP withdrawal

• Oxygen Desaturation Index (ODI)

  Change from baseline in ODI after 2 weeks of CPAP withdrawal

Study Arms (2)

CPAP therapy

ACTIVE COMPARATOR

Continuous positive airway pressure therapy

Device: Continuous positive airway pressure device

Sham CPAP

SHAM COMPARATOR

Sham- Continuous positive airway pressure

Device: Continuous positive airway pressure device

Interventions

Continuous positive airway pressure device DEVICE

(ResMed Spirit S8)

CPAP therapy; Sham CPAP

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Objectively confirmed OSA (at the time of original diagnosis) with an oxygen desaturation index (ODI) and apnoea-hypopnoea-index (AHI) of ≥20/h.
• Currently an oxygen desaturation index (≥4% dips) of ≥15/h during an ambulatory nocturnal pulse oximetry performed on the last night of a four-night period off CPAP.
• Treated with CPAP for more than 12 months
• Device usage \>4h per night, \>80% of the last 365 days, and AHI\<10 with treatment (according to CPAP machine download data).
• Age between 20 and 75 years.
• Written informed consent as documented by signature.

You may not qualify if:

• Previous ischemic or haemorrhagic stroke; known cerebral aneurysm or arterio-venous malformation.
• Carotid artery stenosis \> 70%
• Use of alpha- and beta-adrenergic blocking medication, antianginal medications, triptans, selective COX-inhibitors
• Unstable, untreated coronary or peripheral artery disease, severe arterial hypertension or hypotension (\>180/110 or \<90/60mmHg)
• Implanted pacemaker or internal cardiac defibrillator
• Changes in medication during the trial
• Previous ventilatory failure (awake SpO2 \<93% andPaCO2\>6kPa).
• Obesity hypoventilation syndrome, COPD
• Previously diagnosed with Cheyne-Stokes breathing.
• Current professional driver or any previous sleep related driving accidents.
• Caffeine or nicotine abuse 12 hours before measurements

Sponsors & Collaborators

• University of Zurich: lead

Study Sites (1)

Pulmonary Division, University Hospital Zurich

Zurich, 8091, Switzerland

Location

Related Publications (2)

• Thiel S, Gaisl T, Lettau F, Boss A, Winklhofer S, Kohler M, Rossi C. Impact of hypertension on cerebral microvascular structure in CPAP-treated obstructive sleep apnoea patients: a diffusion magnetic resonance imaging study. Neuroradiology. 2019 Dec;61(12):1437-1445. doi: 10.1007/s00234-019-02292-z. Epub 2019 Sep 16.

  PMID: 31529145 DERIVED

• Thiel S, Haile SR, Peitzsch M, Schwarz EI, Sievi NA, Kurth S, Beuschlein F, Kohler M, Gaisl T. Endocrine responses during CPAP withdrawal in obstructive sleep apnoea: data from two randomised controlled trials. Thorax. 2019 Nov;74(11):1102-1105. doi: 10.1136/thoraxjnl-2019-213522. Epub 2019 Aug 29.

  PMID: 31467191 DERIVED

MeSH Terms

Conditions

Sleep Apnea, Obstructive; Stroke

Condition Hierarchy (Ancestors)

Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Malcolm Kohler, MD

  University of Zurich

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2015
• First Posted: July 9, 2015
• Study Start: June 1, 2015
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: April 6, 2018

Record last verified: 2018-04

Locations

CH (1)