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Trial registered on ANZCTR


Registration number
ACTRN12615000122550
Ethics application status
Approved
Date submitted
21/01/2015
Date registered
11/02/2015
Date last updated
22/01/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Obesity Hypoventilation Syndrome and Neurocognitive Dysfunction
Scientific title
An observational study comparing neurocognitive function of obese patients with sleep disordered breathing with and without chronically elevated arterial carbon dioxide levels before and after 3 months of positive pressure mask therapy.
Secondary ID [1] 285726 0
Nil
Universal Trial Number (UTN)
U1111-1164-4500
Trial acronym
The CO2 Project
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obesity Hypoventilation Syndrome 293607 0
Obstructive Sleep Apnoea 293608 0
Condition category
Condition code
Respiratory 293895 293895 0 0
Sleep apnoea
Diet and Nutrition 294483 294483 0 0
Obesity

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Neurocognitive function testing, sleep studies and EEG analysis, arterial blood gas and questionnaires will be performed before and after 3 months of positive airway pressure therapy.

Positive airway pressure will be titrated to determine optimal pressure settings for each patient. Either CPAP or Bilevel will be applied via a full face or nasal mask interface for the 3 month duration. Patients will be advised to use this therapy each night. Positive airway treatment is part of standard care.

In addition to monthly phone calls to monitor use of therapy, positive airway pressure devices will be downloaded at 3 months to obtain objective compliance data.

Participants are patients with obesity hypoventilation syndrome (OHS). By definition, they will have elevated carbon dioxide levels (hypercapnia).


Intervention code [1] 290681 0
Not applicable
Comparator / control treatment
Patients with obstructive sleep apnoea (OSA) without hypercapnia. These patients are those that do not meet the criteria for obesity hypoventilation syndrome.

Patients with OSA (controls) will also receive positive airway pressure therapy as per standard of care. The pressure will be set and compliance monitored as described for the OHS group.
Control group
Active

Outcomes
Primary outcome [1] 293672 0
Psychomotor Vigilance Task (PVT)

Timepoint [1] 293672 0
3 months after near normalization of carbon dioxide levels with positive airway pressure therapy (PAP)
Secondary outcome [1] 311558 0
Changes in awake blood gases
Timepoint [1] 311558 0
Blood gases will be analyzed before and after near normalization of carbon dioxide levels with positive airway pressure therapy (PAP) at the initial visit and 3 months after PAP use. A single sample will be obtained at each visit.
Secondary outcome [2] 312711 0
Treatment compliance
Timepoint [2] 312711 0
Objective compliance data will be downloaded from the CPAP/Bilevel machine at the end of the study duration at 3 months.
Secondary outcome [3] 312712 0
Changes in quality of life and sleepiness
Timepoint [3] 312712 0
This will be assessed pre and post 3 months of positive airway pressure using the Epworth Sleepiness Score questiomnaire and Functional outcomes of sleep questionnaire. These tests will take less than 15 minutes to complete at each visit.
Secondary outcome [4] 312713 0
Neurocognitive test results
Timepoint [4] 312713 0
Testing will occur pre and post 3 months of positive airway pressure therapy using computer based neurocognitive tests. The complete battery will take 50 minutes and will occur at both visits.
Secondary outcome [5] 312714 0
EEG parameters including Delta/Alpha ratio (EEG activation) and power spectral analysis
Timepoint [5] 312714 0
These parameters will be obtained from the sleep studies performed overnight. Information will be extracted and analyzed from each sleep study (pre and post intervention).
Secondary outcome [6] 324679 0
AusEd steering deviation from median lane position
Timepoint [6] 324679 0
Testing will occur pre and 3 months post positive airway pressure use.

Eligibility
Key inclusion criteria
1. Age 18 – 75 years old
2. Written informed consent
3. Daytime CO2 > 45 (OHS) or < 45 (Control)
4. Evidence of definite OSA on polysomnography, with an AHI >20 /hr OR evidence of sleep hypoventilation if AHI <20/hr

* Increase in TcCO2 to a value > 55mmHg for >10 mins or

* Increase in TcCO2 > 10 mmHg (compared with awake PaCO2) to a value > 50 mmHg for > 10 mins)

5. BMI>40kg/m2
6. pH is in the normal range for chronic hypercapnia
7. FEV1/FVC ratio > 0.7
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Major psychiatric, neurological disorder or head injury
2. Neuromuscular disease or lung disease
3. FEV1/FVC ratio <0.7
4. Uncontrolled medical conditions including cardiac failure
5. Alcohol consumption >30 g/day or on medications potentially affecting cognitive testing or EEG recordings such as opiates, benzodiazepines, anti-depressants and anticonvulsants (unless on stable low dose).
6. Not proficient in English


Study design
Purpose
Duration
Selection
Timing
Statistical methods / analysis
Prior to treatment, OHS subjects will be compared with the normocapnic OSA group with respect to the cognitive outcomes tested, using linear regression modelling. The effect of group will be examined, controlling for OSA severity, BMI, gender, age, and years of education. Response to therapy (mean change with 95% confidence limits) will be assessed by paired-t-test, and also by mixed effects modelling to control for changes in weight and also explore the impact of change in pCO2 on the change in performance.

A total of 60 patients will be studied. We estimate there will be 20 in the OHS group and 40 in the OSA group (ie 30-40% OHS). This will provide 80% power to detect a 8.6 cm difference in steering deviation between the two groups (assume SD=11 cm, alpha 0.05, controlling for circadian effects, this difference of 8.6 cm ~ 14.5 hours of extended wakefulness). Allowing for 20% loss to follow-up, the sample is powered to detect a 10.8 cm change in AusEd steering deviation (~ 17 h extended wakefulness, at 80% power, within subject SD=10.2 cm).

Reference:
Wong KK et al. Comparing the neurocognitive effects of 40 h sustained wakefulness in patients with untreated OSA and healthy controls. J Sleep Res. 2008. 17(3):322-30

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 3202 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 8983 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 290300 0
Self funded/Unfunded
Name [1] 290300 0
Project interventions are part of routine care. Equipment for neurocognitive testing is readily available within hospital premises.
Address [1] 290300 0
N/A
Country [1] 290300 0
Primary sponsor type
Individual
Name
Sheila Sivam
Address
Department of Respiratory and Sleep Medicine
Royal Prince Alfred Hospital
Missenden Road
Camperdown 2050 NSW
Country
Australia
Secondary sponsor category [1] 289010 0
None
Name [1] 289010 0
N/A
Address [1] 289010 0
N/A
Country [1] 289010 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292005 0
SLHD Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 292005 0
Mailing Address:
c/- Research Development Office
Royal Prince Alfred Hospital
Missenden Road
CAMPERDOWN NSW 2050


Ethics committee country [1] 292005 0
Australia
Date submitted for ethics approval [1] 292005 0
25/11/2014
Approval date [1] 292005 0
20/02/2015
Ethics approval number [1] 292005 0

Summary
Brief summary
Neurocognitive impairments in Obstructive Sleep Apnoea (OSA) are likely related to a combination of factors including low oxygen levels during sleep (hypoxia), sleep fragmentation and possibly elevated carbon dioxide levels (hypercapnia). The latter, unlike hypoxia, has not been explored in depth and is often viewed as an innocent bystander. Early detection of hypercapnia may be an important step in the prevention of neurocognitive dysfunction in Obesity Hypoventilation Syndrome (OSA/OHS). In this study, neurocognitive function of patients with sleep disordered breathing will be assessed before and after 3 months of positive pressure mask therapy.

Hypothesis
1. Patients with OHS exhibit greater cognitive impairment than obese patients with obstructive sleep apnea (OSA), but without daytime hypercapnia.
2. Patients with sleep hypoventilation have less sleep fragmentation but greater neurocognitive impairment arising from a longer exposure to hypercapnia.
3. Although correction of hypercapnia with PAP treatment will at least partially improve cognitive function, patients with OHS may remain impaired relative to treated OSA patients without hypercapnia.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 53026 0
Dr Sheila Sivam
Address 53026 0
DEPT OF RESPIRATORY AND SLEEP MEDICINE
LEVEL 11, BUILDING 75
ROYAL PRINCE ALFRED HOSPITAL
MISSENDEN ROAD
CAMPERDOWN NSW 2050
Country 53026 0
Australia
Phone 53026 0
+61 2 9515 8708
Fax 53026 0
Email 53026 0
sheila.sivam@sydney.edu.au
Contact person for public queries
Name 53027 0
Dr Sheila Sivam
Address 53027 0
DEPT OF RESPIRATORY AND SLEEP MEDICINE
LEVEL 11, BUILDING 75
ROYAL PRINCE ALFRED HOSPITAL
MISSENDEN ROAD
CAMPERDOWN NSW 2050
Country 53027 0
Australia
Phone 53027 0
+61 2 9515 8708
Fax 53027 0
Email 53027 0
sheila.sivam@sydney.edu.au
Contact person for scientific queries
Name 53028 0
Dr Sheila Sivam
Address 53028 0
DEPT OF RESPIRATORY AND SLEEP MEDICINE
LEVEL 11, BUILDING 75
ROYAL PRINCE ALFRED HOSPITAL
MISSENDEN ROAD
CAMPERDOWN NSW 2050
Country 53028 0
Australia
Phone 53028 0
+61 2 9515 8708
Fax 53028 0
Email 53028 0
sheila.sivam@sydney.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary