None listed
Conditions
Brief summary
Obstructive sleep apnea (OSA) is a common cause of daytime sleepiness, impaired cognition, and has a 3 -13 times increased risk of motor vehicle crashes and double the rate of work accidents. This neurobehavioural dysfunction has a critical impact on health and society. One of the major challenges in dealing with this problem is the difficulty in clinically assessing neurobehavioural dysfunction such as impairment in driving ability. Many patients underestimate their impairment and there is wide inter-individual variability in how patients are affected by sleepiness and its consequences. For example, patients with sleep studies showing severe OSA may report few symptoms while others with apparent mild disease exhibit severe sleepiness. Unravelling this problem of inter-individual variability demands better assessment tools as conventional metrics such as sleep studies are uninformative. What is urgently needed are biomarkers, measured at a single or very limited time points that better reflect the individual risk of vigilance failure such as impaired driving. In this study, simulated driving and other performance tasks will be administered during a load of prolonged wakefulness extending throughout the night to unmask variation in neurobehavoural function in OSA. Performance under these conditions will be related to practically deployable biomarkers (or combination of biomarkers) measured at baseline. We have compelling preliminary data on brain bioenergetics (magnetic resonance imaging), quantitative electroencephalogram (qEEG) and cortical activation (event related potentials) as candidate biomarkers for neurobehavioural impairment in OSA. Such biomarkers would also be potentially valuable as tests to monitor treatment effectiveness or a phenotyping tools in molecular and genetic discovery in OSA.
Interventions
85 patients with moderate-severe obstructive sleep apnea will be recruited to undergo an experimental laboratory protocol following a screening visit and after obtaining informed consent.
One week of actigraphy and sleep-wake diary and indoor-outdoor activity logs, will be performed prior to the test visit to measure sleep hours and activities at home, and participants will be advised to observe regular sleep hours with 8-hours in bed.
The experimental protocol visit consists:
- baseline sleep
85 patients with moderate-severe obstructive sleep apnea will be recruited to undergo an experimental laboratory protocol following a screening visit and after obtaining informed consent. One week of actigraphy and sleep-wake diary and indoor-outdoor activity logs, will be performed prior to the test visit to measure sleep hours and activities at home, and participants will be advised to observe regular sleep hours with 8-hours in bed. The experimental protocol visit consists: - baseline sleep study followed by 28 hours of extended wakefulness challenge (EWC) with detailed assessment including: Primary performance outcomes measure -Three 90 minute computerised AusEd driving simulator tasks measured at Time 1 (9.30am, 3.5 hours awake), Time 2 (2.30am, 20.5 hours awake) and Time 3 (8.30am, 26.5 hours awake) Secondary performance outcome measure -10 minute psychomotor vigilance test (PVT) measures every 2 hours throughout the EWC starting from midday. Primary Predictor Variables -Baseline sleep study is performed from 10pm-6am (EEG data will be subjected to spectral power analysis as part of data processing/analysis) -Auditory Event Related potentials (ERP) data will be collected at between 8.30-9.30am (baseline assessment only) -Resting awake EEG during a 7 minute Karolinska Drowsiness Test measure every 2 hours throughout the EWC startinf at midday -Magnetic Resonance Spectroscopy/Diffusion Tensor Imaging occurs within 1 week prior to laboratory EWC visit (assessed at baseline only) Secondary Predictor Variables -mRNA expression profiles from baseline to end of EWC (blood/mRNA samples collected at 6.15am upon awakening and 6.15am the following morning after 24hours of wakefulness -Posture/Balance control assessments measured every 2 hours throughout the EWC starting at midday -Peripheral Blood Pressure measures every 2 hours throughout the EWC starting at midday Computerised performance tests measure every 2 hours through out the EWC starting at midday : - Working memory (N-back 1,2,3) - Visuomotor skills (Digit Symbol Substitution Task) - 4 Choice Reaction Time Task -Central Blood Pressure and Pulse Wave Analysis (PWA) measures every 2 hours throughout the EWC starting at midday -Statistical Learning Task measured at baseline (8.30pm prior to baseline sleep study) and at 8.30pm 24 hours later. -Actigraphy variables (actigraphy data collected 1 week prior to EWC) -PSG sleep study variables (collected during the baseline sleep study just prior to EWC) -Genetic polymorphisms (genetic analysis from blood samples collected at start and end of EWC will occur at the completion of the study) -Inflammatory marker profiles (from blood sample analysis collected at start and end of EWC will occur at the completion of the study) -Brief Smell Identification Test (B-SIT) is collected at baseline only at 7.30pm prior to baseline sleep study -State anxiety questionnaire administered every 2 hours throughout the EWC starting at midday -Karolinska Sleepiness Scale administered every 2 hours throughout the EWC starting at midday
Sponsors
Woolcock Institute of Medical Research
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Prevention
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
25 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Age 25-65 years Weight <150kg PSG confirmed moderate to severe obstructive sleep apnea with an Apnea Hypopnea Index (AHI) of =15 events/hr and an Oxygen Desaturation Index (ODI) of =3% with =10 events/hr Ability to read and speak English Ability to perform neurobehavioural tests
Exclusion criteria
Other PSG confirmed sleep disorders OSA patients with clinically significant uncontrolled co-morbidity such as: cardiac failure, hypertension, hypercapnia, COPD, Type 1 diabetes History of head injury or psychiatric/neurological disorders: clinical depression, epilepsy, mania or psychosis, stroke Currently using CNS active medications/drugs such as: anti-depressives, anti-psychotics, opiates, antihistamines
Outcome results
None listed