COPDORACLENCT06377332
Biomarkers of Dementia in Chronic Sleep and Breathing Disorders
An observational study of COPD and Overlap Syndrome, run by Woolcock Institute of Medical Research at 1 site in Australia.
Trial summary
Chronic obstructive pulmonary disease (COPD), obstructive sleep apnoea (OSA) and overlap syndrome are associated with obstructions in breathing and disturbed sleep. Chronic breathing disruptions and poor sleep may lead to cognitive impairment and brain changes linked with early neurodegenerative processes. Read more about this study
- Who is it for?
- Ages 40 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- COPD, Overlap Syndrome, OSA
- What is being tested?
- High density electroencephalogram (HdEEG), Functional near infrared spectroscopy (fNIRS) and Magnetic resonance imaging (MRI)
- Type of treatment
- Pill or oral medicine
- How many people
- 104 participants
- Where
- 1 siteAustralia
- Study dates
- 1 Dec 2023to 1 Jul 2025
- Phase
- Observational
- 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 40 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: The study population involves four groups: controls, OSA, COPD and overlap syndrome (OVS). All participants will meet all inclusion criteria for their group and none of the exclusion criteria.
Who may be able to join
- Control:
- Males and females;
- Aged 40-65 years;
- Able to give informed consent;
- Able to perform neuropsychological and cognitive testing;
- Fluent in English.
Show all 30Show fewer
- OSA:
- Males and females;
- Aged 40-65 years;
- Oximetry confirmed moderate to severe OSA based on the oxygen desaturation index (ODI) ≥15/hr;
- Able to give informed consent;
- Ability to perform neuropsychological and cognitive testing;
- Fluent in English.
- 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:
- Males and females;
- Aged 40-65 years;
- Oximetry confirmed moderate to severe OSA based on the oxygen desaturation index (ODI) ≥15/hr;
- 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.
Who cannot join
- Dementia diagnosis;
- At home or overnight oxygen therapy;
- Asthma diagnosis (identified with lung function bronchodilator);
- Current antipsychotic use;
- BMI > 40;
- PAP use or OSA treatment in the last 2 months;
Show all 14Show fewer
- Recent COPD exacerbation with change in symptomology (hospitalisation and/or steroids and/or antibiotics) within 6 weeks;
- Awake supine oxygen saturations of < 93%;
- Sleep disorders including narcolepsy, idiopathic hypersomnia (IH), moderate-severe restless leg syndrome (RLS) or REM behaviour disorder (RBD);
- Other major comorbidities (other lung diseases, neurodegenerative disease, brain injury, severe mental illness, PTSD);
- Uncontrolled depression (impacting daily life, no use of medications or engagement with psychotherapy- dictated by physician);
- Malignancies (basal cell carcinoma accepted);
- Any contraindication for MRI.
- New York Heart Association (NYHA) score of IV or hospitalisation from heart failure in the last 6 months.
Trial locations and contacts
1 site in 1 country.
Australia1 site, 1 recruiting
- Recruiting
The Woolcock Institute of Medical Research
Sydney, New South Wales, 2113
Angela D'Rozario, PhD, 02 9850 3246, angela.drozario@mq.edu.au
Laura Harris, MScMed, 02 9805 3194, laura.harris@woolcock.org.au
About this study
Chronic obstructive pulmonary disease (COPD), obstructive sleep apnoea (OSA) and overlap syndrome are associated with obstructions in breathing and disturbed sleep.
Chronic breathing disruptions and poor sleep may lead to cognitive impairment and brain changes linked with early neurodegenerative processes. As such, identifying early markers of cognitive impairment and dementia risk in individuals with chronic respiratory and sleep breathing disorders is crucial for understanding how these diseases may contribute to accelerated brain ageing. This study will comprehensively measure sleep, lung function, cognitive performance and blood-based markers of dementia risk and inflammation. The investigators will use innovative technologies to identify biomarkers of cognitive impairment and dementia risk in people with chronic sleep and breathing disorders. The investigators will also investigate the relationships between disrupted sleep and abnormal breathing and the brain. This research may also inform future early interventions to improve cognition and brain health in chronic sleep and respiratory disease.
Read the detailed description
Neurodegeneration that is present in dementia is caused, in part, by neuroinflammation, cerebral vascular damage and oxidative stress. Intermittent hypoxia and hypercapnia, as seen in patients with chronic obstructive pulmonary disease (COPD), obstructive sleep apnoea (OSA) and overlap syndrome, cause neuroinflammation and sleep fragmentation. As a result, key biomarkers of cytokine tumour necrosis factor-alpha (TNF-a), C-reactive protein (CRP), eosinophils, CD8+ and CD4+ T cells, interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-1 beta (IL-1B), nuclear factor kappa beta (NF-kB) and hypoxia-inducible factor (HIF) infiltrate the central nervous system (CNS), perpetuating neuroinflammation through the presence of microglia which cause oxidative and nitrosative stress.
Key inflammatory and dementia-based biomarkers will be collected in the investigation of this association including but not limited to Aβ40/42 ratio and ptau217.
This study consists of an observational cross-sectional design with the utilisation of blood collection, lung function testing, MRI, HdEEG, fNIRS and neurocognitive assessment. Participants will be selected into the study differentially based on the target group, with OSA criteria requiring an ODI > 15, COPD criteria requiring a GOLD 2 minimum, FEV1 ≥50%, < 80% predicted; FEV1/FVC < 0.7 with a 10- pack year smoking history and overlap syndrome criteria requiring a combination of ODI > 15 and GOLD 2 minimum, FEV1 ≥50%, < 80% predicted; FEV1/FVC < 0.7, with a 10-pack year smoking history. Participants will be 40 to 65 years old. Controls will have no diagnosis of OSA, COPD or overlap syndrome and have an English fluency. In order to test the hypotheses, the design of a cross-sectional study will allow us to a) examine the relationships between sleep and breathing metrics and cognition and blood-based markers of dementia pathology b) examine the relationships between potential intermediates of compromised sleep and breathing with the primary cognitive and dementia risk outcomes c) compare sleep, lung function, brain health, cognition and inflammatory markers between OSA, COPD, overlap syndrome and control groups.
- Conditions
- COPD, Overlap Syndrome, OSA
- Being tested
- High density electroencephalogram (HdEEG), Functional near infrared spectroscopy (fNIRS), Magnetic resonance imaging (MRI), Blood collection, Neuropsychological battery
- Keywords
- Biomarkers, Observational, Cross-Sectional
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High density electroencephalogram (HdEEG)Diagnostic test
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.
Functional near infrared spectroscopy (fNIRS)Diagnostic test
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.
Magnetic resonance imaging (MRI)Diagnostic test
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.
Blood collectionBiological
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.
Neuropsychological batteryDiagnostic test
- Montreal Cognitive Assessment (MoCA):
- Test of Premorbid Functioning (TOPF):
- Rey Auditory Verbal Learning Test (RAVLT):
- D-KEFS Colour Word Interference Test (D-CWIT):
- Trail Making Test (TMT):
- Symbol Digit Modalities Test (SDMT) - Oral Version:
- RAVLT 20-minute recall
- Controlled Oral Word Association Test (COWAT):
QuestionnairesOther
- Epworth Sleepiness Scale (ESS)
- PROMIS sleep questionnaire 8a,
- PROMIS sleep questionnaire 8b
- EQ-5D-5L
- Insomnia Severity Index (ISI)
- Pittsburgh Sleep Quality Index (PSQ-I)
- St George's Respiratory Questionnaire (SGRQ)
- COPD Assessment Test (CAT)
Pulmonary Function Test (PFT)Diagnostic test
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.
Cognitive AssessmentOther
The following cognitive assessments will be administered using a digital format on CANTAB:
- 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.
- Reaction Time (RTI) Used to assess processing and psychomotor speed and is applicable in the assessment of general cognitive function and Alzheimer's disease.
- 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.
- 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.
Polysomnogram (PSG)Diagnostic test
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Diagnostic Test: High density electroencephalogram (HdEEG); Diagnostic Test: Functional near infrared spectroscopy (fNIRS); Diagnostic Test: Magnetic resonance imaging (MRI); Biological: Blood collection; Diagnostic Test: Neuropsychological battery; Other: Questionnaires; Diagnostic Test: Pulmonary Function Test (PFT); Other: Cognitive Assessment; Diagnostic Test: Polysomnogram (PSG) | |
| 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. Receives: Diagnostic Test: High density electroencephalogram (HdEEG); Diagnostic Test: Functional near infrared spectroscopy (fNIRS); Diagnostic Test: Magnetic resonance imaging (MRI); Biological: Blood collection; Diagnostic Test: Neuropsychological battery; Other: Questionnaires; Diagnostic Test: Pulmonary Function Test (PFT); Other: Cognitive Assessment; Diagnostic Test: Polysomnogram (PSG) | |
| 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. Receives: Diagnostic Test: High density electroencephalogram (HdEEG); Diagnostic Test: Functional near infrared spectroscopy (fNIRS); Diagnostic Test: Magnetic resonance imaging (MRI); Biological: Blood collection; Diagnostic Test: Neuropsychological battery; Other: Questionnaires; Diagnostic Test: Pulmonary Function Test (PFT); Other: Cognitive Assessment; Diagnostic Test: Polysomnogram (PSG) | |
| Control | Males and females; Aged 40-65 years; Able to give informed consent; Able to perform neuropsychological and cognitive testing; Fluent in English. Receives: Diagnostic Test: High density electroencephalogram (HdEEG); Diagnostic Test: Functional near infrared spectroscopy (fNIRS); Diagnostic Test: Magnetic resonance imaging (MRI); Biological: Blood collection; Diagnostic Test: Neuropsychological battery; Other: Questionnaires; Diagnostic Test: Pulmonary Function Test (PFT); Other: Cognitive Assessment; Diagnostic Test: Polysomnogram (PSG) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Scores on the Montreal Cognitive Assessment (MoCA) neuropsychological assessment for dementia risk.
MoCA scores of 18 to 25 indicate mild cognitive impairment, 10 to 17 indicate moderate cognitive impairment and scores below 10 indicate severe cognitive impairment.
Associations between MoCA and night-time hypoxemia / sleep fragmentation in the entire sample.
Measured: Cross-sectional/baseline only
Blood levels of amyloid beta (Aβ40/Aβ42 ratio).
Associations between blood levels of Aβ (Aβ40/Aβ42 ratio) and night-time hypoxemia / sleep fragmentation in the entire sample.
Measured: Cross-sectional/baseline only
Secondary outcomes (24)
Absolute Electroencephalographic (EEG) Power During Non-Rapid Eye Movement (NREM) Sleep.
Spectral power of delta (1-4.5 Hz), theta (4.5-8 Hz), alpha (8-12 Hz), sigma (12-15 Hz), beta (15-25 Hz), and gamma (25-40 Hz) frequency ranges. Associations between absolute Electroencephalographic (EEG) Power During Non-Rapid Eye Movement (NREM) Sleep and night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Measured: Cross-sectional/baseline only
Brain tissue oxygenation during cognitive tasks and sleep.
Brain tissue oxygenation during sleep as measured by oxygenated and deoxygenated hemoglobin using functional Near Infrared Spectroscopy (fNIRS). Associations between brain tissue oxygenation and night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Measured: Cross-sectional/baseline only
Hypoxemia as measured by pulse oximetry.
Overnight hypoxemia measured by pulse oximetry through nocturnal readings of blood oxygen saturation (SpO2). Associations between night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Measured: Cross-sectional/baseline only
Sleep Fragmentation
EEG arousal index (events per minute of total sleep time) measured during polysomnography. Associations between night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Measured: Cross-sectional/baseline only
Assessment of premorbid functioning and preinjury through the Test of Premorbid Functioning (TOPF).
Neuropsychological Test: A z-score of -0.75 indicates low-average premorbid functioning, z= -1.40 indicates borderline poor premorbid functioning and inferior premorbid functioning spans from z=-2.05 to -3.65. Associations between TOPF scores and night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Measured: Cross-sectional/baseline only
Assessment of verbal learning and memory through the Rey Auditory Verbal Learning Test (RAVLT).
Neuropsychological Test: RAVLT scores between groups. Scores ≤ z= -1.0 across two domains indicate poor performance. Immediate verbal learning is assessed by summing trials 1 to 5, Learning is assessed from trial 5 minus trial 1, and Forgetting is assessed through trial five minus the delayed recall trial. Associations between RAVLT scores and night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Measured: Cross-sectional/baseline only
Assessment of mild forms of cognitive dysfunction through Delis Kaplan Executive Functioning System (D-CEFS) neuropsychological assessment.
Neuropsychological Test: Differences in scores between groups across the four trials. Greater time taken to complete the trials results in higher scores which indicate worse performance. Associations between D-CEFS scores night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Measured: Cross-sectional/baseline only
Assessment of speed of processing and executive functioning through the Trail Making Test (TMT).
Neuropsychological Test: Differences in TMT scores between groups. Greater time taken to complete the tests results in higher scores which indicate worse performance. A TMT trial A score of ≥78 seconds and a TMT trial B score of ≥273 seconds indicates deficiency. Associations between TMT scores night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Measured: Cross-sectional/baseline only
Assessment of verbal fluency through the Controlled Oral Word Association Test (COWAT).
Neuropsychological Test: Differences in the COWAT scores between groups. The more acceptable words stated across all four trials, the better the performance in the test. Associations between COWAT scores and night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Measured: Cross-sectional/baseline only
Assessment of attention, perceptual speed, motor speed and visual scanning through the Symbol Digits Modalities Test (SDMT).
Neuropsychological Test: Differences in the scores on the SDMT between groups. Scores on the SDMT range from 1 to 110, with higher scores indicating better performance over the 90-second trial. Associations between SDMT scores and night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Measured: Cross-sectional/baseline only
Blood levels of fibrinogen.
Differences in the blood levels of fibrinogen between groups. Associations between fibrinogen and night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Measured: Cross-sectional/baseline only
Blood levels of clusterin.
Differences in the blood levels of clusterin between groups. Associations between clusterin and night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Measured: Cross-sectional/baseline only
Blood levels of 8-isoprostane
Differences in the blood levels of 8-isoprostane between groups. Associations between 8-isoprostane and night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Measured: Cross-sectional/baseline only
Blood levels of C-reactive protein (CRP)
Differences in the blood levels of CRP between groups. Associations between CRP and night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Measured: Cross-sectional/baseline only
Blood levels of erythrocyte sedimentation rate (ESR).
Differences in the blood levels of ESR between groups. Associations between ESR and night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Measured: Cross-sectional/baseline only
Blood levels of plasma tau.
Differences in the blood levels of plasma tau between groups. Associations between plasma-tau and night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Measured: Cross-sectional/baseline only
Blood levels of neurofilament light chain (NFL).
Differences in the blood levels of NFL between groups. Associations between NFL and night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Measured: Cross-sectional/baseline only
Blood levels of Glial fibrillary acidic protein (GFAP).
Differences in the blood levels of GFAP between groups. Associations between GFAP and night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Measured: Cross-sectional/baseline only
Blood levels of Apolipoprotein E gene (APOE-4).
Differences in the blood levels of APOE-4 between groups. Associations between APOE-4 and night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Measured: Cross-sectional/baseline only
Blood levels of interleukin-8 (IL-8).
Differences in the blood levels of IL-8 between groups. Associations between IL-8 and night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Measured: Cross-sectional/baseline only
Blood levels of interleukin-6 (IL-6).
Differences in the blood levels of IL-6 between groups. Associations between IL-6 and night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Measured: Cross-sectional/baseline only
Blood levels of tumor necrosis factor alpha (TNFα).
Differences in the blood levels of TNFα between groups. Associations between TNFα and night-time hypoxemia / sleep fragmentation in the entire sample and between groups.
Measured: Cross-sectional/baseline only
Blood levels of amyloid beta (Aβ40/Aβ42 ratio).
Associations between blood levels of Aβ (Aβ40/Aβ42 ratio) and night-time hypoxemia / sleep fragmentation between groups.
Measured: Cross-sectional/baseline only
Scores on the Montreal Cognitive Assessment (MoCA) neuropsychological assessment for dementia risk.
MoCA scores of 18 to 25 indicate mild cognitive impairment, 10 to 17 indicate moderate cognitive impairment and scores below 10 indicate severe cognitive impairment.
Associations between MoCA and night-time hypoxemia / sleep fragmentation between groups.
Measured: Cross-sectional/baseline only
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2024
- Study start1 Dec 2023
- Primary completion1 Jul 2025 (estimated)
- Study completion1 Jul 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COPDStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 104 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Woolcock Institute of Medical Research
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06377332
- Sponsor's protocol ID
- X23-0330
- Acronym
- ORACLE
- Status last verified
- Nov 2023
- First submitted
- 6 Nov 2023
- Last updated
- 22 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: Data pertaining to the OSA group will be shared with protocol number X22-0213 (Project: OSA-D; within The Woolcock Institute of Medical Research)
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biomarkers of Dementia in Chronic Sleep and Breathing Disorders
- ClinicalTrials.gov ID
- NCT06377332
- Acronym / sponsor ID
- ORACLE / X23-0330
- Conditions
- COPD, Overlap Syndrome, OSA
- Keywords
- Biomarkers, Observational, Cross-Sectional
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 104 participants (estimated)
- Lead sponsor
- Woolcock Institute of Medical ResearchUniversity, hospital or other
- Study start
- 1 Dec 2023 (actual)
- Primary completion
- 1 Jul 2025 (estimated)
- Study completion
- 1 Jul 2025 (estimated)
- First posted
- 22 Apr 2024 (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.
Chronic obstructive pulmonary disease (COPD), obstructive sleep apnoea (OSA) and overlap syndrome are associated with obstructions in breathing and disturbed sleep.
Chronic breathing disruptions and poor sleep may lead to cognitive impairment and brain changes linked with early neurodegenerative processes. As such, identifying early markers of cognitive impairment and dementia risk in individuals with chronic respiratory and sleep breathing disorders is crucial for understanding how these diseases may contribute to accelerated brain ageing. This study will comprehensively measure sleep, lung function, cognitive performance and blood-based markers of dementia risk and inflammation. The investigators will use innovative technologies to identify biomarkers of cognitive impairment and dementia risk in people with chronic sleep and breathing disorders. The investigators will also investigate the relationships between disrupted sleep and abnormal breathing and the brain. This research may also inform future early interventions to improve cognition and brain health in chronic sleep and respiratory disease.
Detailed description
Neurodegeneration that is present in dementia is caused, in part, by neuroinflammation, cerebral vascular damage and oxidative stress. Intermittent hypoxia and hypercapnia, as seen in patients with chronic obstructive pulmonary disease (COPD), obstructive sleep apnoea (OSA) and overlap syndrome, cause neuroinflammation and sleep fragmentation. As a result, key biomarkers of cytokine tumour necrosis factor-alpha (TNF-a), C-reactive protein (CRP), eosinophils, CD8+ and CD4+ T cells, interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-1 beta (IL-1B), nuclear factor kappa beta (NF-kB) and hypoxia-inducible factor (HIF) infiltrate the central nervous system (CNS), perpetuating neuroinflammation through the presence of microglia which cause oxidative and nitrosative stress.
Key inflammatory and dementia-based biomarkers will be collected in the investigation of this association including but not limited to Aβ40/42 ratio and ptau217.
This study consists of an observational cross-sectional design with the utilisation of blood collection, lung function testing, MRI, HdEEG, fNIRS and neurocognitive assessment. Participants will be selected into the study differentially based on the target group, with OSA criteria requiring an ODI > 15, COPD criteria requiring a GOLD 2 minimum, FEV1 ≥50%, < 80% predicted; FEV1/FVC < 0.7 with a 10- pack year smoking history and overlap syndrome criteria requiring a combination of ODI > 15 and GOLD 2 minimum, FEV1 ≥50%, < 80% predicted; FEV1/FVC < 0.7, with a 10-pack year smoking history. Participants will be 40 to 65 years old. Controls will have no diagnosis of OSA, COPD or overlap syndrome and have an English fluency. In order to test the hypotheses, the design of a cross-sectional study will allow us to a) examine the relationships between sleep and breathing metrics and cognition and blood-based markers of dementia pathology b) examine the relationships between potential intermediates of compromised sleep and breathing with the primary cognitive and dementia risk outcomes c) compare sleep, lung function, brain health, cognition and inflammatory markers between OSA, COPD, overlap syndrome and control groups.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Chronic Obstructive Pulmonary Disease (COPD) | – | Diagnostic Test: High density electroencephalogram (HdEEG), Diagnostic Test: Functional near infrared spectroscopy (fNIRS), Diagnostic Test: Magnetic resonance imaging (MRI), Biological: Blood collection, Diagnostic Test: Neuropsychological battery, Other: Questionnaires, Diagnostic Test: Pulmonary Function Test (PFT), Other: Cognitive Assessment, Diagnostic Test: Polysomnogram (PSG)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) | – | Diagnostic Test: High density electroencephalogram (HdEEG), Diagnostic Test: Functional near infrared spectroscopy (fNIRS), Diagnostic Test: Magnetic resonance imaging (MRI), Biological: Blood collection, Diagnostic Test: Neuropsychological battery, Other: Questionnaires, Diagnostic Test: Pulmonary Function Test (PFT), Other: Cognitive Assessment, Diagnostic Test: Polysomnogram (PSG)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) | – | Diagnostic Test: High density electroencephalogram (HdEEG), Diagnostic Test: Functional near infrared spectroscopy (fNIRS), Diagnostic Test: Magnetic resonance imaging (MRI), Biological: Blood collection, Diagnostic Test: Neuropsychological battery, Other: Questionnaires, Diagnostic Test: Pulmonary Function Test (PFT), Other: Cognitive Assessment, Diagnostic Test: Polysomnogram (PSG)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 | – | Diagnostic Test: High density electroencephalogram (HdEEG), Diagnostic Test: Functional near infrared spectroscopy (fNIRS), Diagnostic Test: Magnetic resonance imaging (MRI), Biological: Blood collection, Diagnostic Test: Neuropsychological battery, Other: Questionnaires, Diagnostic Test: Pulmonary Function Test (PFT), Other: Cognitive Assessment, Diagnostic Test: Polysomnogram (PSG)Males and females; Aged 40-65 years; Able to give informed consent; Able to perform neuropsychological and cognitive testing; Fluent in English. |
Who may qualify
- Ages
- 40 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- The study population involves four groups: controls, OSA, COPD and overlap syndrome (OVS). All participants will meet all inclusion criteria for their group and none of the exclusion criteria.
Key inclusion criteria (30 listed)
- Males and females;
- Aged 40-65 years;
- Able to give informed consent;
- Able to perform neuropsychological and cognitive testing;
- Fluent in English.
Key exclusion criteria (14 listed)
- Dementia diagnosis;
- At home or overnight oxygen therapy;
- Asthma diagnosis (identified with lung function bronchodilator);
- Current antipsychotic use;
- BMI > 40;
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 |
|---|---|---|
| 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. | Diagnostic test | Chronic Obstructive Pulmonary Disease (COPD), Control, Obstructive Sleep Apnoea (OSA), Overlap Syndrome (OVS) |
| 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. | Diagnostic test | Chronic Obstructive Pulmonary Disease (COPD), Control, Obstructive Sleep Apnoea (OSA), Overlap Syndrome (OVS) |
| 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. | Diagnostic test | Chronic Obstructive Pulmonary Disease (COPD), Control, Obstructive Sleep Apnoea (OSA), Overlap Syndrome (OVS) |
| Blood collectionA 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. | Biological | Chronic Obstructive Pulmonary Disease (COPD), Control, Obstructive Sleep Apnoea (OSA), Overlap Syndrome (OVS) |
| Neuropsychological batteryA. 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): | Diagnostic test | Chronic Obstructive Pulmonary Disease (COPD), Control, Obstructive Sleep Apnoea (OSA), Overlap Syndrome (OVS) |
| Questionnaires1. 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) | Other | Chronic Obstructive Pulmonary Disease (COPD), Control, Obstructive Sleep Apnoea (OSA), Overlap Syndrome (OVS) |
| 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. | Diagnostic test | Chronic Obstructive Pulmonary Disease (COPD), Control, Obstructive Sleep Apnoea (OSA), Overlap Syndrome (OVS) |
| Cognitive AssessmentThe 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. | Other | Chronic Obstructive Pulmonary Disease (COPD), Control, Obstructive Sleep Apnoea (OSA), Overlap Syndrome (OVS) |
| 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. | Diagnostic test | Chronic Obstructive Pulmonary Disease (COPD), Control, Obstructive Sleep Apnoea (OSA), Overlap Syndrome (OVS) |
Primary outcome
Scores on the Montreal Cognitive Assessment (MoCA) neuropsychological assessment for dementia risk.
Time frame: Cross-sectional/baseline only
MoCA scores of 18 to 25 indicate mild cognitive impairment, 10 to 17 indicate moderate cognitive impairment and scores below 10 indicate severe cognitive impairment. Associations between MoCA and night-time hypoxemia / sleep fragmentation in the entire sample.
Blood levels of amyloid beta (Aβ40/Aβ42 ratio).
Time frame: Cross-sectional/baseline only
Associations between blood levels of Aβ (Aβ40/Aβ42 ratio) and night-time hypoxemia / sleep fragmentation in the entire sample.
24 secondary outcomes
Absolute Electroencephalographic (EEG) Power During Non-Rapid Eye Movement (NREM) Sleep.
Time frame: Cross-sectional/baseline only
Brain tissue oxygenation during cognitive tasks and sleep.
Time frame: Cross-sectional/baseline only
Hypoxemia as measured by pulse oximetry.
Time frame: Cross-sectional/baseline only
Sleep Fragmentation
Time frame: Cross-sectional/baseline only
Assessment of premorbid functioning and preinjury through the Test of Premorbid Functioning (TOPF).
Time frame: Cross-sectional/baseline only
Assessment of verbal learning and memory through the Rey Auditory Verbal Learning Test (RAVLT).
Time frame: Cross-sectional/baseline only
Assessment of mild forms of cognitive dysfunction through Delis Kaplan Executive Functioning System (D-CEFS) neuropsychological assessment.
Time frame: Cross-sectional/baseline only
Assessment of speed of processing and executive functioning through the Trail Making Test (TMT).
Time frame: Cross-sectional/baseline only
Assessment of verbal fluency through the Controlled Oral Word Association Test (COWAT).
Time frame: Cross-sectional/baseline only
Assessment of attention, perceptual speed, motor speed and visual scanning through the Symbol Digits Modalities Test (SDMT).
Time frame: Cross-sectional/baseline only
Blood levels of fibrinogen.
Time frame: Cross-sectional/baseline only
Blood levels of clusterin.
Time frame: Cross-sectional/baseline only
Blood levels of 8-isoprostane
Time frame: Cross-sectional/baseline only
Blood levels of C-reactive protein (CRP)
Time frame: Cross-sectional/baseline only
Blood levels of erythrocyte sedimentation rate (ESR).
Time frame: Cross-sectional/baseline only
Blood levels of plasma tau.
Time frame: Cross-sectional/baseline only
Blood levels of neurofilament light chain (NFL).
Time frame: Cross-sectional/baseline only
Blood levels of Glial fibrillary acidic protein (GFAP).
Time frame: Cross-sectional/baseline only
Blood levels of Apolipoprotein E gene (APOE-4).
Time frame: Cross-sectional/baseline only
Blood levels of interleukin-8 (IL-8).
Time frame: Cross-sectional/baseline only
Blood levels of interleukin-6 (IL-6).
Time frame: Cross-sectional/baseline only
Blood levels of tumor necrosis factor alpha (TNFα).
Time frame: Cross-sectional/baseline only
Blood levels of amyloid beta (Aβ40/Aβ42 ratio).
Time frame: Cross-sectional/baseline only
Scores on the Montreal Cognitive Assessment (MoCA) neuropsychological assessment for dementia risk.
Time frame: Cross-sectional/baseline only
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2024.
- Individual participant dataSharing planned: Yes. Data pertaining to the OSA group will be shared with protocol number X22-0213 (Project: OSA-D; within The Woolcock Institute of Medical Research)
Related trials for COPD
Active, not recruiting
Symptoms and Functions in Patients With COPD and Chronic Bronchitis Switching From CIG to THS
COPD, Smoking
Not yet recruitingPhase 2/3
An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Not yet recruiting
The Aim of the Study is to Decipher the Alterations in Signalling Pathways of Skeletal Muscle Stem Cells (Satellite Cells (SCs)) in Individuals With COPD, as Well as to Examine the Effect of Exercise Training on SCs.
COPD (Chronic Obstructive Pulmonary Disease), Sarcopenia in Elderly
Not yet recruitingPhase 2
Study of Treprostinil Administered Via Soft Mist Inhaler (SMI) in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Active, not recruitingPhase 1
A Study for GSK3862995B in Healthy Participants and Participants With Chronic Obstructive Pulmonary Disease
Pulmonary Disease, Chronic Obstructive
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of COPD and Overlap Syndrome, run by Woolcock Institute of Medical Research at 1 site in Australia.
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 30 inclusion and 14 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: status not confirmed, as of the sponsor's last update on 22 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Angela D'Rozario (02 9850 3246, angela.drozario@mq.edu.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Scores on the Montreal Cognitive Assessment (MoCA) neuropsychological assessment for dementia risk. (time frame: Cross-sectional/baseline only). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 Apr 2024.