Clinical trial NCT03472612: OSA Recurrence in CPAP Withdrawal
Official title: Pathophysiology of Obstructive Sleep Apnoea Recurrence During Continuous Positive Airway Pressure Therapy Withdrawal
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: OSA
Keywords: OSA
CPAP
upper airway collapse
neural respiratory drive
Lead sponsor: Guy's and St Thomas' NHS Foundation Trust
Sponsor class: OTHER
First posted: 2018-03-21
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: Continuous positive airway pressure (CPAP) therapy is the most effective Treatment for obstructive sleep apnoea (OSA ). However, adherence to CPAP is often limited. There are established and emerging treatment alternatives to CPAP available, however, they are usually less effective than CPAP. To develop novel treatment methods and to predict who will respond to which treatment, the mechanism underlying obstructive sleep apnoea and different patient types should be described. Especially the contribution of the upper airway function and central respiratory control should be studied for this purpose. In a prospective interventional study, patients with OSA effectively treated with CPAP will undergo physiologic measurements during a two week period off CPAP to define the pathophysiological mechanisms associated with OSA recurrence. This knowledge could facilitate individually tailored treatment and improve therapy adherence and patient outcomes.

Detailed description: Obstructive sleep apnoea (OSA) is a highly prevalent sleep-related breathing disorder characterised by a repetitive collapse of the pharynx during sleep, which results in apnoea or hypopnoea associated with oxygen desaturations and arousal from sleep. Continuous positive airway pressure (CPAP) is the gold standard treatment. Treatment success depends on regular CPAP usage. However, low adherence to CPAP is a frequent problem. It has recently been shown that OSA does not re-occur immediately in all OSA patients upon CPAP therapy withdrawal and that there are different patterns of recurrence of OSA as indicated by repeated sleep studies. So far, the mechanisms of OSA recurrence upon CPAP therapy withdrawal are incompletely understood. Upper airway collapsibility and neuromuscular tone, pharyngeal oedema and inflammation, neural respiratory drive, sleep stage and position may play a role.

In a prospective interventional study, patients with OSA effectively treated with CPAP will undergo physiologic measurements during a two week period off CPAP to define the pathophysiological mechanisms associated with OSA recurrence. In particular, we will investigate the effects of CPAP withdrawal on neural respiratory drive and upper airway function. Inpatient sleep studies and assessments will be performed at baseline (day 0) on CPAP and at follow-up upon CPAP withdrawal (day 14). At the end of the trial patients will return to their established CPAP therapy.

We hypothesise that CPAP withdrawal results in different patterns of OSA recurrence defined by neural respiratory drive and upper airway function. The aim of the proposed project is to study the mechanisms of OSA recurrence by using a validated CPAP withdrawal model. Knowledge on recurrence patterns and different phenotypes of OSA could facilitate individually tailored treatment of OSA and improved therapy adherence and patient outcomes.

Eligibility criteria: Inclusion criteria:

* Age ≥18-80 years. Objectively confirmed OSA with an apnoea-hypopnoea- index (AHI) or an oxygen desaturation index (ODI) of ≥20/h at the time of diagnosis (obstructive events).
* Effectively treated with CPAP for \> 6 months (AHI on CPAP \< 5/h, CPAP usage \> 4 hours/night \> 70% of the days).

Exclusion criteria:

* Moderate to severe obstructive (FEV1/FVC \< lower limit of normal and FEV1 \< 70% predicted) or restrictive lung disease (FVC \< 60% predicted).
* Daytime pCO2 \> 6 kPa (45 mmHg).
* Central Sleep Apnoea/Cheyne Stokes Respiration. Unstable heart failure, untreated coronary artery disease, severe arterial hypertension (resting blood pressure \>180/110 mmHg).
* Co-existing non-respiratory sleep disorder (by history).
* Opioid or sedative use. Alcohol abuse.
* Current professional driver or comparable profession.

Primary outcomes:
measure: Change in neural respiratory drive (NRD) during sleep upon CPAP therapy withdrawal
timeFrame: 2 weeks
Secondary outcomes:
measure: Pharyngeal critical occlusion pressure during sleep (Pcrit)
timeFrame: 2 weeks
measure: Forced oscillation technique (FOT)
timeFrame: 2 weeks
measure: Negative expiratory pressure (NEP)
timeFrame: 2 weeks
measure: Pharyngeal oedema
timeFrame: 2 weeks
measure: Forced expiratory volume in 1 second
timeFrame: 2 weeks
measure: Forced vital capacity
timeFrame: 2 weeks
measure: Recurrence pattern of OSA defined by the nightly obstructive respiratory events (apnoea-hypopnoea-index)
timeFrame: 2 weeks
measure: Recurrence pattern of OSA defined by the nightly obstructive respiratory events (oxygen desaturation index)
timeFrame: 2 weeks
measure: Home and office blood pressure
timeFrame: 2 weeks
measure: Home and office heart rate
timeFrame: 2 weeks
measure: Epworth Sleepiness Scale Score (ESS)
timeFrame: 2 weeks
measure: Fatigue Severity Sclae (FSS)
timeFrame: 2 weeks
measure: Stanford Sleepiness Scale (SSS)
timeFrame: 2 weeks
measure: Functional Outcomes of Sleep Questionnaire (FOSQ)
timeFrame: 2 weeks
measure: Association between ODI (recurrence pattern of OSA) and neural respiratory drive (NRD)
timeFrame: 2 weeks
Other outcomes:
measure: Association between different measures of (upper) airway function, namely Pcrit, FOT, NEP and FEV1/FVC
timeFrame: 2 weeks
Locations:
city: London
country: United Kingdom
facility: Guys and St Thomas NHS Foundation Trust
Study officials:
affiliation: Guy's and St Thomas' NHS Foundation Trust
name: Joerg Steier, MD Ph
role: PRINCIPAL_INVESTIGATOR
References: