PAIR Study-PAP And IOP Relationship: Study 1 (PAIR)

June 5, 2018 updated by: Papworth Hospital NHS Foundation Trust

The PAIR Study. Positive Airway Pressure and Intraocular Relationship: IOP Response to a Short-term Application of CPAP

Lowering of the pressure in the eye (intraocular pressure, IOP) is the only proven treatment for Primary Open-angle Glaucoma (POAG). However, even effective reduction of IOP by pharmacological or surgical means does not always change the course of the disease or prevent the onset of glaucoma. Some people with POAG also suffer from Obstructive Sleep Apnoea (OSA), an increasingly common sleep disorder which is known to affect heart and blood vessels, and may contribute to glaucoma progression. OSA is treated with Continuous Positive Airway Pressure (CPAP); however using this type of breathing support may raise IOP.

This study aims to establish whether a short-term application of CPAP in awake subjects leads to an increase in IOP. Patients with treated POAG, patients with newly diagnosed untreated POAG and control subjects without glaucoma will be included. CPAP will be applied at several different pressure levels for a total of 2 hours during which IOP and ocular perfusion pressure (OPP) will be measured. If CPAP is shown to raise IOP or alter OPP it could be necessary to assess available alternative treatment options for OSA.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Primary open-angle glaucoma (POAG) is a progressive optic neuropathy characterized by specific optic disc changes and associated visual field defects. Estimated prevalence is 3.0%, making it the leading cause of irreversible blindness worldwide. Intraocular pressure (IOP) is the only proven modifiable risk factor for the development and progression of POAG, but even effective reduction of IOP by pharmacological or surgical means does not always change the course of the disease or prevent some people from developing glaucoma.

OSA is a sleep-related breathing disorder (SBD) caused by complete (apnoea) or partial (hypopnoea) narrowing of the upper airway, resulting in disturbed sleep and intermittent oxygen desaturations. These in turn have negative impact on cardiovascular system and potentially other organs. OSA is treated by continuous positive airway pressure (CPAP) applied by a nasal or a full face mask which maintains patency of the upper airway. CPAP is the first line treatment for moderately severe and severe OSA and, among currently used treatment modalities, it is also the most effective one. The prevalence of OSA continues to increase linked with the rising global incidence of obesity, though many remain undiagnosed. A recent study from the United States estimated that 35% of people between the ages of 50 and 70 years suffer from OSA, and approximately 12% may require treatment.

OSA and OAG are, therefore, two common conditions which may coexist in a significant proportion of patients. In fact, some studies indicate increased prevalence of OAG in patients with OSA, which is in line with a suspected causative role of OSA in glaucoma.

People with OAG and concomitant OSA associated with the relevant symptoms, particularly daytime sleepiness, currently receive standard treatment with CPAP. However, the impact of CPAP on their glaucoma is unknown. There are concerns that CPAP increases IOP, currently the only modifiable factor in glaucoma, though the evidence for this is limited. The exact mechanisms of the possible IOP-raising effect of CPAP are not clear. The favoured hypothesis is CPAP leads to increases in intrathoracic pressure, which in turn raises pressure in the venous circulation and a reduction in the aqueous humour outflow through the episcleral veins and ultimately IOP increase. A similar mechanism is believed to be responsible for IOP elevation in the transition from an upright to supine position in which venous drainage is reduced.

The relationship between the level of pressure used in CPAP treatment and IOP has not been studied. It is unknown if IOP increases in correlated way to CPAP or whether there is no straightforward correlation. If the first is true, application of CPAP only up to a certain pressure level would be safe and perhaps the threshold to use bi-level PAP should be lower in patients with glaucoma. If, however, IOP changes are a matter of individual response to CPAP, perhaps dependent on the severity of OSA or BMI, a routine measurement of the pressure should be performed once CPAP is started. This is currently not a part of standard clinical practice. It is also possible that CPAP set within the usual pressure range does not influence IOP or its effect is not mediated by simple mechanical pressure transmission.

Therefore understanding the influence of CPAP on IOP is important as it may inform the management of people with OSA and concomitant glaucoma. If CPAP is shown to raise IOP or alter ocular perfusion pressure (OPP) to levels that pose clinical risk it will be necessary to assess available alternative treatment options for OSA.

This is a prospective physiological controlled study which will assess IOP response to several different CPAP levels applied for short periods in wakefulness in three groups of people: POAG patients established on treatment (treated glaucoma group), newly diagnosed treatment naïve POAG patients (untreated glaucoma group) and control subjects without glaucoma (control subjects).

Study Type

Interventional

Enrollment (Actual)

46

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Cambridgeshire
      • Huntingdon, Cambridgeshire, United Kingdom, PE29 6NT
        • Hinchingbrooke Hospital NHS Foundation Trust

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

38 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age >40 years
  • Able to give informed consent and attend for the study visit.

Exclusion Criteria:

  • Previous surgical treatment for glaucoma
  • Current or recent (within 4 weeks) CPAP or non-invasive ventilation (NIV) use
  • History of face mask intolerance
  • Any facial lesion preventing safe CPAP mask application
  • Allergy to silicone
  • Any contraindications to rebound tonometry, including: corneal scarring, microphthalmos, buphthalmos, nystagmus, keratoconus, abnormal central corneal thickness, corneal ectasia, active corneal infection, , and corneal dystrophies.
  • Concomitant eye diseases known to affect IOP, including: treated wet age related macular degeneration (ARMD), central retinal vein occlusion (CRVO), branch retinal vein occlusion (BRVO), uveitis and diabetic retinopathy.
  • Significant lung disease (including previous pneumothorax, previous or current respiratory failure, severe Chronic Obstructive Pulmonary Disease (COPD), bullous lung disease, difficult to control asthma, acute chest infection)
  • Significant heart disease (including heart failure, unstable arrhythmias, pulmonary hypertension)
  • Untreated upper gastro-intestinal obstruction
  • Acute infectious diseases
  • Known or suspected pregnancy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treated glaucoma
POAG patients established on treatment
Other: Application of continuous positive airway pressure (CPAP)
CPAP will be delivered at 4 different pressure levels (6, 10, 13 and 16cmH2O) in a randomly allocated order
Experimental: Untreated
Newly diagnosed treatment naïve POAG patients
Other: Application of continuous positive airway pressure (CPAP)
CPAP will be delivered at 4 different pressure levels (6, 10, 13 and 16cmH2O) in a randomly allocated order
Active Comparator: Control
Control subjects without glaucoma
Other: Application of continuous positive airway pressure (CPAP)
CPAP will be delivered at 4 different pressure levels (6, 10, 13 and 16cmH2O) in a randomly allocated order

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Intraocular pressure (IOP)
Time Frame: On completion of study visit- 3 hours
Difference between baseline IOP and IOP on each CPAP level
On completion of study visit- 3 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Relationship between Continuous Positive Airway Pressure (CPAP) level and IOP
Time Frame: On completion of study visit - 3hours
Correlation between level of CPAP applied and IOP
On completion of study visit - 3hours
Minimum CPAP level required to increase IOP
Time Frame: On completion of study visit- 3 hours
Minimum CPAP level required to increase IOP
On completion of study visit- 3 hours
Differences in change in IOP between each study group
Time Frame: On completion of study visit - 3 hours
Differences in IOP change (ΔIOP; IOPCPAP -IOPbaseline) at each CPAP level between the study groups
On completion of study visit - 3 hours
Relationship between changes in IOP after CPAP with BMI
Time Frame: On completion of study visit - 3 hours
Correlation between IOP change (ΔIOP; IOPCPAP -IOPbaseline) in response to CPAP with BMI
On completion of study visit - 3 hours
Relationship between changes in IOP after CPAP with lung volume (Vital Capacity-VC)
Time Frame: On completion of study visit - 3 hours
Correlation between IOP change (ΔIOP; IOPCPAP -IOPbaseline) in response to CPAP with Vital Capacity
On completion of study visit - 3 hours
Relationship between changes in IOP after CPAP with glaucoma severity.
Time Frame: On completion of study visit - 3 hours
Correlation between IOP change (ΔIOP; IOPCPAP -IOPbaseline) in response to CPAP with glaucoma severity
On completion of study visit - 3 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Papworth Hospital NHS Foundation Trust

Collaborators

Hinchingbrooke Hospital NHS Trust

Investigators

  • Principal Investigator: Dariusz Wozniak, Papworth Hospital NHS Foundation Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 15, 2017

Primary Completion (Actual)

January 5, 2018

Study Completion (Actual)

January 5, 2018

Study Registration Dates

First Submitted

April 13, 2017

First Submitted That Met QC Criteria

April 20, 2017

First Posted (Actual)

April 25, 2017

Study Record Updates

Last Update Posted (Actual)

June 7, 2018

Last Update Submitted That Met QC Criteria

June 5, 2018

Last Verified

June 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P02133

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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