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The Effects of Trazodone on Sleep Apnea Severity

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ClinicalTrials.gov Identifier: NCT01817907
Recruitment Status : Completed
First Posted : March 26, 2013
Results First Posted : February 24, 2017
Last Update Posted : February 24, 2017
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
David Andrew Wellman, Brigham and Women's Hospital

Brief 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.

Condition or disease Intervention/treatment Phase
Sleep Apnea, Obstructive Drug: Placebo pill Drug: Trazodone Not Applicable

Detailed 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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: The Effects of Trazodone on the Severity of Obstructive Sleep Apnea
Study Start Date : March 2013
Actual Primary Completion Date : April 2014
Actual Study Completion Date : December 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sleep Apnea

Arm Intervention/treatment
Placebo Comparator: Placebo
Subjects will receive a sugar pill during their placebo night sleep study.
Drug: Placebo pill
Subjects will receive a sugar pill during the placebo arm
Other Name: Sugar pill

Active Comparator: Trazodone
Subjects will receive trazodone during their treatment night sleep study
Drug: Trazodone
Subjects will receive trazodone during one of their treatment arm studies




Primary Outcome Measures :
  1. Apnea-Hypopnea Index [ Time Frame: Participants will be assessed on 2 nights over an average period of 2 weeks. ]
    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).


Secondary Outcome Measures :
  1. Arousal Threshold (cmH2O) [ Time Frame: Participants will be assessed on 2 nights over an average period of 2 weeks. ]
    Subjects will have an epiglottic pressure catheter placed during their sleep studies. We will use the swing in the epiglottic pressure trace just prior to arousal to calculate the respiratory drive stimulus that is associated with an a respiratory induced arousal.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01817907


Locations
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United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Brigham and Women's Hospital
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Principal Investigator: David A Wellman, MD, PhD Brigham and Women's Hospital

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: David Andrew Wellman, Principal Investigator, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT01817907     History of Changes
Other Study ID Numbers: BWH-2009P001862
P01HL095491-01A1 ( U.S. NIH Grant/Contract )
First Posted: March 26, 2013    Key Record Dates
Results First Posted: February 24, 2017
Last Update Posted: February 24, 2017
Last Verified: January 2017

Keywords provided by David Andrew Wellman, Brigham and Women's Hospital:
Apnea- Hypopnea index
Arousal Threshold

Additional relevant MeSH terms:
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Apnea
Sleep Apnea Syndromes
Sleep Apnea, Obstructive
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Nervous System Diseases
Trazodone
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Antidepressive Agents, Second-Generation
Antidepressive Agents