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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06377332




Registration number
NCT06377332
Ethics application status
Date submitted
6/11/2023
Date registered
22/04/2024

Titles & IDs
Public title
Biomarkers of Dementia in Chronic Sleep and Breathing Disorders
Scientific title
Biomarkers of Dementia in Chronic Sleep and Breathing Disorders
Secondary ID [1] 0 0
X23-0330
Universal Trial Number (UTN)
Trial acronym
ORACLE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
COPD 0 0
Overlap Syndrome 0 0
OSA 0 0
Condition category
Condition code
Neurological 0 0 0 0
Dementias
Neurological 0 0 0 0
Alzheimer's disease

Intervention/exposure
Study type
Observational
Patient registry
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Diagnosis / Prognosis - High density electroencephalogram (HdEEG)
Diagnosis / Prognosis - Functional near infrared spectroscopy (fNIRS)
Diagnosis / Prognosis - Magnetic resonance imaging (MRI)
Treatment: Other - Blood collection
Diagnosis / Prognosis - Neuropsychological battery
Other interventions - Questionnaires
Diagnosis / Prognosis - Pulmonary Function Test (PFT)
Other interventions - Cognitive Assessment
Diagnosis / Prognosis - Polysomnogram (PSG)

Chronic Obstructive Pulmonary Disease (COPD) - Males and females; Aged 40-65 years; COPD confirmed by diagnosis or a positive lung function test (GOLD 2 minimum, FEV1

=50%, \< 80% predicted; FEV1/FVC \< 0.7); 10-pack year smoking history; Able to perform neuropsychological and cognitive testing; Fluent in English.

Overlap Syndrome (OVS) - Males and females; Aged 40-65 years; Oximetry confirmed moderate to severe OSA based on the oxygen desaturation index (ODI) =15/hr OR defined by polysomnography (PSG) AHI of = 15 COPD confirmed by diagnosis or a positive lung function test (GOLD 2 minimum, FEV1

=50%, \< 80% predicted; FEV1/FVC \< 0.7); 10-pack year smoking history; Able to perform neuropsychological and cognitive testing; Fluent in English.

Obstructive Sleep Apnoea (OSA) - Males and females; Aged 40-65 years; Oximetry confirmed moderate to severe OSA based on the oxygen desaturation index (ODI) =15/hr OR defined by polysomnography (PSG) AHI of = 15. Able to give informed consent; Ability to perform neuropsychological and cognitive testing; Fluent in English.

Control - Males and females; Aged 40-65 years; Able to give informed consent; Able to perform neuropsychological and cognitive testing; Fluent in English.


Diagnosis / Prognosis: High density electroencephalogram (HdEEG)
High-density electroencephalography (HdEEG) will be utilised in the investigation of sleep-mediated neuronal functions in controls, OSA, COPD and overlap syndrome and the association with accelerated brain ageing and cognitive impairment.

Diagnosis / Prognosis: Functional near infrared spectroscopy (fNIRS)
Functional near infrared spectroscopy (fNIRS) is one of the most advanced techniques in measuring brain oxygen content and hemodynamic activity. This information indirectly displays neuronal activity and provides a novel opportunity understand brain oxygenation, neurodegenerative diseases, and cognitive function.

Diagnosis / Prognosis: Magnetic resonance imaging (MRI)
Magnetic resonance imaging (MRI) will be utilised to assess potential structural neuronal changes associated with neurodegenerative disease in those with COPD, OSA and overlap syndrome. MRI has the capacity to provide vital information regarding neuroimaging standards in cerebral vascular damage such as white matter hyperintensities (WMH), lacunes, cerebral microbleeds, brain atrophy and subcortical infarct. Through the utility of MRI sequences such as T1 and T2 weighted imaging, diffusion weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) and resting-state fMRI (rs-fMRI), the investigators will assess neurodegenerative-related structural brain changes in individuals with COPD, OSA and overlap syndrome and examine the differences between these target groups.

Treatment: Other: Blood collection
A fasting 50mL blood sample will be collected at the experimental visit in the morning following the overnight sleep study. Blood samples will be processed after collection and stored at -80 degrees for future batch analyses. Analyses will include markers for inflammation and dementia including but not limited to ptau217 and beta amyloid. Routine blood analyses will be conducted on 17.5mL of the sample collected for baseline measures. Routine blood analyses includes lipid profile, glucose studies, insulin, high-sensitivity C-reactive protein (hs-CRP), iron studies, thyroid function, b12/folate, homocysteine, prolactin, calcium, full blood count and biochemistry panel for the OSA, COPD and overlap syndrome groups.

Routine blood analyses for controls include glucose studies, lipid profile, hs-CRP and biochemistry panel.

Diagnosis / Prognosis: Neuropsychological battery
A. Montreal Cognitive Assessment (MoCA):

B. Test of Premorbid Functioning (TOPF):

C. Rey Auditory Verbal Learning Test (RAVLT):

D. D-KEFS Colour Word Interference Test (D-CWIT):

E. Trail Making Test (TMT):

F. Symbol Digit Modalities Test (SDMT) - Oral Version:

G. RAVLT 20-minute recall

H. Controlled Oral Word Association Test (COWAT):

Other interventions: Questionnaires
1. Epworth Sleepiness Scale (ESS)
2. PROMIS sleep questionnaire 8a,
3. PROMIS sleep questionnaire 8b
4. EQ-5D-5L
5. Insomnia Severity Index (ISI)
6. Pittsburgh Sleep Quality Index (PSQ-I)
7. St George's Respiratory Questionnaire (SGRQ)
8. COPD Assessment Test (CAT)

Diagnosis / Prognosis: Pulmonary Function Test (PFT)
Full pulmonary function testing will be conducted in control, COPD, OSA and overlap syndrome groups. Full lung function testing will include spirometry with pre and post bronchodilator, oscillometry, lung diffusion testing (DLCO) and lung volumes.

Other interventions: Cognitive Assessment
The following cognitive assessments will be administered using a digital format on CANTAB:

1. Motor Screening Task (MOT) Used to assess sensorimotor function and comprehension and is applicable in the assessment of general cognitive function, Alzheimer's disease and cerebrovascular disease. This task acts as a practice trial for the subsequent tasks.
2. Reaction Time (RTI) Used to assess processing and psychomotor speed and is applicable in the assessment of general cognitive function and Alzheimer's disease.
3. Paired Associate Learning (PAL) Used to assess visual episodic memory and is applicable in the assessment of general cognitive function, Alzheimer's disease, Parkinson's disease and cerebrovascular disease.
4. Spatial Working Memory (SWM) Used to assess working memory and strategy and is applicable in the assessment of general cognitive function, Alzheimer's disease and cerebrovascular disease.

Diagnosis / Prognosis: Polysomnogram (PSG)
During the sleep study, physiological signals are recorded to capture eye movements (electrooculogram, EOG) and chin muscle movements (electromyogram, EMG). A nasal airflow piece, two respiratory inductance plethysmography (RIP) bands and an oximeter probe on the finger will monitor breathing and oxygen levels in the blood. Electrocardiogram (ECG), leg movements, sleeping position and snoring are also recorded.
Intervention code [1] 0 0
Diagnosis / Prognosis
Intervention code [2] 0 0
Treatment: Other
Intervention code [3] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Scores on the Montreal Cognitive Assessment (MoCA) neuropsychological assessment for dementia risk.
Timepoint [1] 0 0
Cross-sectional/baseline only
Primary outcome [2] 0 0
Blood levels of amyloid beta (Aß40/Aß42 ratio).
Timepoint [2] 0 0
Cross-sectional/baseline only
Secondary outcome [1] 0 0
Absolute Electroencephalographic (EEG) Power During Non-Rapid Eye Movement (NREM) Sleep.
Timepoint [1] 0 0
Cross-sectional/baseline only
Secondary outcome [2] 0 0
Brain tissue oxygenation during cognitive tasks and sleep.
Timepoint [2] 0 0
Cross-sectional/baseline only
Secondary outcome [3] 0 0
Hypoxemia as measured by pulse oximetry.
Timepoint [3] 0 0
Cross-sectional/baseline only
Secondary outcome [4] 0 0
Sleep Fragmentation
Timepoint [4] 0 0
Cross-sectional/baseline only
Secondary outcome [5] 0 0
Assessment of premorbid functioning and preinjury through the Test of Premorbid Functioning (TOPF).
Timepoint [5] 0 0
Cross-sectional/baseline only
Secondary outcome [6] 0 0
Assessment of verbal learning and memory through the Rey Auditory Verbal Learning Test (RAVLT).
Timepoint [6] 0 0
Cross-sectional/baseline only
Secondary outcome [7] 0 0
Assessment of mild forms of cognitive dysfunction through Delis Kaplan Executive Functioning System (D-CEFS) neuropsychological assessment.
Timepoint [7] 0 0
Cross-sectional/baseline only
Secondary outcome [8] 0 0
Assessment of speed of processing and executive functioning through the Trail Making Test (TMT).
Timepoint [8] 0 0
Cross-sectional/baseline only
Secondary outcome [9] 0 0
Assessment of verbal fluency through the Controlled Oral Word Association Test (COWAT).
Timepoint [9] 0 0
Cross-sectional/baseline only
Secondary outcome [10] 0 0
Assessment of attention, perceptual speed, motor speed and visual scanning through the Symbol Digits Modalities Test (SDMT).
Timepoint [10] 0 0
Cross-sectional/baseline only
Secondary outcome [11] 0 0
Blood levels of fibrinogen.
Timepoint [11] 0 0
Cross-sectional/baseline only
Secondary outcome [12] 0 0
Blood levels of clusterin.
Timepoint [12] 0 0
Cross-sectional/baseline only
Secondary outcome [13] 0 0
Blood levels of 8-isoprostane
Timepoint [13] 0 0
Cross-sectional/baseline only
Secondary outcome [14] 0 0
Blood levels of C-reactive protein (CRP)
Timepoint [14] 0 0
Cross-sectional/baseline only
Secondary outcome [15] 0 0
Blood levels of erythrocyte sedimentation rate (ESR).
Timepoint [15] 0 0
Cross-sectional/baseline only
Secondary outcome [16] 0 0
Blood levels of plasma tau.
Timepoint [16] 0 0
Cross-sectional/baseline only
Secondary outcome [17] 0 0
Blood levels of neurofilament light chain (NFL).
Timepoint [17] 0 0
Cross-sectional/baseline only
Secondary outcome [18] 0 0
Blood levels of Glial fibrillary acidic protein (GFAP).
Timepoint [18] 0 0
Cross-sectional/baseline only
Secondary outcome [19] 0 0
Blood levels of Apolipoprotein E gene (APOE-4).
Timepoint [19] 0 0
Cross-sectional/baseline only
Secondary outcome [20] 0 0
Blood levels of interleukin-8 (IL-8).
Timepoint [20] 0 0
Cross-sectional/baseline only
Secondary outcome [21] 0 0
Blood levels of interleukin-6 (IL-6).
Timepoint [21] 0 0
Cross-sectional/baseline only
Secondary outcome [22] 0 0
Blood levels of tumor necrosis factor alpha (TNFa).
Timepoint [22] 0 0
Cross-sectional/baseline only
Secondary outcome [23] 0 0
Blood levels of amyloid beta (Aß40/Aß42 ratio).
Timepoint [23] 0 0
Cross-sectional/baseline only
Secondary outcome [24] 0 0
Scores on the Montreal Cognitive Assessment (MoCA) neuropsychological assessment for dementia risk.
Timepoint [24] 0 0
Cross-sectional/baseline only

Eligibility
Key inclusion criteria
Control:

1. Males and females;
2. Aged 40-65 years;
3. Able to give informed consent;
4. Able to perform neuropsychological and cognitive testing;
5. Fluent in English.

OSA:

1. Males and females;
2. Aged 40-65 years;
3. Oximetry confirmed moderate to severe OSA based on the oxygen desaturation index (ODI) =15/hr;
4. Able to give informed consent;
5. Ability to perform neuropsychological and cognitive testing;
6. Fluent in English.

COPD:

1. Males and females;
2. Aged 40-65 years;
3. COPD confirmed by diagnosis or a positive lung function test (GOLD 2 minimum, FEV1

=50%, < 80% predicted; FEV1/FVC < 0.7);
4. 10-pack year smoking history;
5. Able to perform neuropsychological and cognitive testing;
6. Fluent in English.

Overlap Syndrome:

1. Males and females;
2. Aged 40-65 years;
3. Oximetry confirmed moderate to severe OSA based on the oxygen desaturation index (ODI) =15/hr;
4. COPD confirmed by diagnosis or a positive lung function test (GOLD 2 minimum, FEV1

=50%, < 80% predicted; FEV1/FVC < 0.7);
5. 10-pack year smoking history;
6. Able to perform neuropsychological and cognitive testing;
7. Fluent in English.
Minimum age
40 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Dementia diagnosis;
2. At home or overnight oxygen therapy;
3. Asthma diagnosis (identified with lung function bronchodilator);
4. Current antipsychotic use;
5. BMI > 40;
6. PAP use or OSA treatment in the last 2 months;
7. Recent COPD exacerbation with change in symptomology (hospitalisation and/or steroids and/or antibiotics) within 6 weeks;
8. Awake supine oxygen saturations of < 93%;
9. Sleep disorders including narcolepsy, idiopathic hypersomnia (IH), moderate-severe restless leg syndrome (RLS) or REM behaviour disorder (RBD);
10. Other major comorbidities (other lung diseases, neurodegenerative disease, brain injury, severe mental illness, PTSD);
11. Uncontrolled depression (impacting daily life, no use of medications or engagement with psychotherapy- dictated by physician);
12. Malignancies (basal cell carcinoma accepted);
13. Any contraindication for MRI.
14. New York Heart Association (NYHA) score of IV or hospitalisation from heart failure in the last 6 months.

Study design
Purpose
Duration
Selection
Timing
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/12/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/07/2025
Actual
Sample size
Target
104
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
The Woolcock Institute of Medical Research - Sydney
Recruitment postcode(s) [1] 0 0
2113 - Sydney

Funding & Sponsors
Primary sponsor type
Other
Name
Woolcock Institute of Medical Research
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Angela D'Rozario
Address 0 0
Country 0 0
Phone 0 0
02 9850 3246
Fax 0 0
Email 0 0
angela.drozario@mq.edu.au
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Data pertaining to the OSA group will be shared with protocol number X22-0213 (Project: OSA-D; within The Woolcock Institute of Medical Research)
When will data be available (start and end dates)?
Data will become available upon collection. Data will be available for a minimum of 15 years.
Available to whom?
n=26 obstructive sleep apnoea (OSA) participants will meet all of the OSA inclusion criteria and none of the exclusion criteria.
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT06377332