ANZCTR - Registration

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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]

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

Obstructive Sleep Apnoea

Condition category

Condition code

Respiratory

Sleep apnoea

Diet and Nutrition

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]

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]

Psychomotor Vigilance Task (PVT)

Timepoint [1]

3 months after near normalization of carbon dioxide levels with positive airway pressure therapy (PAP)

Secondary outcome [1]

Changes in awake blood gases

Timepoint [1]

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]

Treatment compliance

Timepoint [2]

Objective compliance data will be downloaded from the CPAP/Bilevel machine at the end of the study duration at 3 months.

Secondary outcome [3]

Changes in quality of life and sleepiness

Timepoint [3]

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]

Neurocognitive test results

Timepoint [4]

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]

EEG parameters including Delta/Alpha ratio (EEG activation) and power spectral analysis

Timepoint [5]

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]

AusEd steering deviation from median lane position

Timepoint [6]

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

Sex

Both males and females

Can healthy volunteers participate?

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

23/02/2015

Actual

23/02/2015

Date of last participant enrolment

Anticipated

Actual

1/06/2017

Date of last data collection

Anticipated

Actual

4/09/2017

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW

Recruitment hospital [1]

Royal Prince Alfred Hospital - Camperdown

Recruitment postcode(s) [1]

2050 - Camperdown

Funding & Sponsors

Funding source category [1]

Self funded/Unfunded

Name [1]

Project interventions are part of routine care. Equipment for neurocognitive testing is readily available within hospital premises.

Address [1]

N/A

Country [1]

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]

None

Name [1]

N/A

Address [1]

N/A

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

SLHD Ethics Review Committee (RPAH Zone)

Ethics committee address [1]

Mailing Address:
c/- Research Development Office
Royal Prince Alfred Hospital
Missenden Road
CAMPERDOWN NSW 2050

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

25/11/2014

Approval date [1]

20/02/2015

Ethics approval number [1]

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

Dr Sheila Sivam

Address

DEPT OF RESPIRATORY AND SLEEP MEDICINE
LEVEL 11, BUILDING 75
ROYAL PRINCE ALFRED HOSPITAL
MISSENDEN ROAD
CAMPERDOWN NSW 2050

Country

Australia

Phone

+61 2 9515 8708

Fax

sheila.sivam@sydney.edu.au

Contact person for public queries

Name

Sheila Sivam

Address

DEPT OF RESPIRATORY AND SLEEP MEDICINE
LEVEL 11, BUILDING 75
ROYAL PRINCE ALFRED HOSPITAL
MISSENDEN ROAD
CAMPERDOWN NSW 2050

Country

Australia

Phone

+61 2 9515 8708

Fax

sheila.sivam@sydney.edu.au

Contact person for scientific queries

Name

Sheila Sivam

Address

DEPT OF RESPIRATORY AND SLEEP MEDICINE
LEVEL 11, BUILDING 75
ROYAL PRINCE ALFRED HOSPITAL
MISSENDEN ROAD
CAMPERDOWN NSW 2050

Country

Australia

Phone

+61 2 9515 8708

Fax

sheila.sivam@sydney.edu.au

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Prevalence of chronic kidney disease in obesity hypoventilation syndrome and obstructive sleep apnoea with severe obesity.	2020	https://dx.doi.org/10.1016/j.sleep.2020.05.017
Embase	Slow-frequency electroencephalography activity during wake and sleep in obesity hypoventilation syndrome.	2020	https://dx.doi.org/10.1093/sleep/zsz214
Embase	Cardiopulmonary coupling and serum cardiac biomarkers in obesity hypoventilation syndrome and obstructive sleep apnea with morbid obesity.	2022	https://dx.doi.org/10.5664/jcsm.9804

N.B. These documents automatically identified may not have been verified by the study sponsor.

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Documents added manually

Documents added automatically