The Effects of Trazodone on Sleep Apnea Severity

Sleep Apnea, Obstructive Clinical Trial

Official title:

The Effects of Trazodone on the Severity of Obstructive Sleep Apnea

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01817907
• Other study ID #: BWH-2009P001862
• Secondary ID: P01HL095491-01A1
• Status: Completed
• Phase: N/A
• First received: November 22, 2012
• Last updated: October 26, 2016
• Start date: March 2013
• Est. completion date: December 2014

Study information

• Verified date: October 2016
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

In Obstructive sleep apnea (OSA), the upper airway closes over and over again during sleep. This leads to disrupted sleep (waking up during the night), daytime sleepiness, and an increased risk for developing high blood pressure. Currently, the best treatment for obstructive sleep apnea is sleeping with a mask that continuously blows air into the nose (i.e. Continuous positive airway pressure [CPAP] treatment). While CPAP treatment stops the upper airway from closing in most people, many people have difficulty sleeping with the mask in place and therefore do not use the CPAP treatment. This research study is being conducted to learn whether using a sedative will improve OSA severity by altering some of the traits that are responsible for the disorder.

Description:

Obstructive sleep apnea (OSA) is characterized by repetitive collapse or 'obstruction' of the pharyngeal airway during sleep. These obstructions result in repetitive hypopneas/apneas and intermittent hypoxia/hypercapnia, as well as surges in sympathetic activity. Such processes disturb normal sleep and impair neurocognitive function, often resulting in excessive daytime sleepiness and decreased quality of life. Furthermore, OSA is associated with cardiovascular morbidity and mortality, making OSA a major health concern.

Current evidence suggests that OSA pathogenesis involves the interactions of at least four physiological traits comprising: 1) the pharyngeal anatomy and its propensity towards collapse. This collapsibility of the upper airway is measured as the critical closing pressure or PCRIT. 2) the ability of the upper airway dilator muscles to activate and reopen the airway during sleep (i.e. neuromuscular compensation) measured as the increase in upper airway electromyography (EMG) activity above the baseline level. 3) the arousal threshold from sleep (i.e. the propensity for hypopneas/apneas to lead to arousal and fragmented sleep) measured as the epiglottic pressure occurring just at the time of arousal and 4) the stability of the ventilatory feedback loop (i.e. loop gain). Continuous positive airway pressure (CPAP) is the most common treatment for OSA but it is often poorly tolerated; only ~50% of patients diagnosed with OSA continue therapy beyond 3 months. Given this limitation, alternative approaches have been tested and have generally focused on the use of oral appliances and upper airway surgery.

In addition to these alternative therapies, the use of pharmacological agents for the treatment of OSA has been gaining widespread interest. Previous data have shown that the non-myorelaxant hypnotic trazodone increases the arousal threshold however its effects on sleep apnea severity remain unclear. Based on studies showing that increasing the arousal threshold with a different hypnotic improves sleep apnea severity, we hypothesize that trazodone will increase the arousal threshold and this will be associated with an improvement in sleep apnea severity.

Therefore the overall aim of this study is to examine the effects that trazodone has on OSA severity.

STUDY DESIGN:

A double-blinded randomized control design will be used. Initially, participants will be randomized to the trazodone or placebo arm where they will have both a clinical polysomnography (PSG) with the addition of an epiglottic pressure cathether. The purpose of the clinical PSG is to determine the severity of OSA (i.e. AHI) and the epiglottic catheter allows the calculation of the arousal threshold to be completed.

During the trazodone arm, participants will be given trazodone (100mg by mouth) to take before bed. During the placebo arm, subjects will be given a placebo to take before bed.

Participants will have at least a 1-week washout period before cross over to the next arm of the study whereby the clinical PSG will be repeated. In total each subject will be studied for 2 nights.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: December 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria for OSA Patients:

• OSA (elevated AHI).

• Age range 18-70 years.

Exclusion Criteria:

• Any known cardiac (apart from treated hypertension), pulmonary (including asthma), renal, neurologic (including epilepsy), neuromuscular, or hepatic disease.

• Susceptible to stomach ulcers.

• Pregnant women.

• History of hypersensitivity to Afrin, Lidocaine, trazodone and/or donepezil.

• History of bleeding diathesis and/or gastrointestinal bleeding.

• Use of any medications that may affect sleep or breathing.

• A psychiatric disorder, other than mild depression; e.g. schizophrenia, bipolar disorder, major depression, panic or anxiety disorders.

• Substantial cigarette (>5/day), alcohol (>3oz/day) or use of illicit drugs.

• More than 10 cups of beverages with caffeine (coffee, tea, soda/pop) per day.

• Desaturations to below 70% lasting greater than 10 seconds in duration per event on polysomnography.

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Apnea
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive

Intervention

Drug:
• Placebo pill
Subjects will receive a sugar pill during the placebo arm
• Trazodone
Subjects will receive trazodone during one of their treatment arm studies

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Brigham and Women's Hospital	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Apnea-Hypopnea Index	The Apnea-Hypopnea Index (AHI) is an index of sleep apnea severity that encompasses the frequency of apneas (cessations in breathing) and hypopneas (reductions in airflow).	Participants will be assessed on 2 nights over an average period of 2 weeks.	No
Secondary	Arousal threshold	Subjects will have an epiglottic pressure catheter placed during their sleep studies. We will use the swing in the pressure trace just prior to arousal to calculate the respiratory drive stimulus that is associated with an a respiratory induced arousal.	Participants will be assessed on 2 nights over an average period of 2 weeks.	No