The Effects of Trazodone on Sleep Apnea Severity

Sponsor
Brigham and Women's Hospital (Other)
Overall Status
Completed
CT.gov ID
NCT01817907
Collaborator
National Heart, Lung, and Blood Institute (NHLBI) (NIH)
15
1
2
21
0.7

Study Details

Study Description

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
N/A

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.

Study Design

Study Type:
Interventional
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 :
Mar 1, 2013
Actual Primary Completion Date :
Apr 1, 2014
Actual Study Completion Date :
Dec 1, 2014

Arms and Interventions

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 Names:
  • 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

    Outcome Measures

    Primary Outcome Measures

    1. Apnea-Hypopnea Index [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) [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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 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

    • Principal Investigator: David A Wellman, MD, PhD, Brigham and Women's Hospital

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    David Andrew Wellman, Principal Investigator, Brigham and Women's Hospital
    ClinicalTrials.gov Identifier:
    NCT01817907
    Other Study ID Numbers:
    • BWH-2009P001862
    • P01HL095491-01A1
    First Posted:
    Mar 26, 2013
    Last Update Posted:
    Feb 24, 2017
    Last Verified:
    Jan 1, 2017
    Keywords provided by David Andrew Wellman, Principal Investigator, Brigham and Women's Hospital
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Placebo First Trazodone First
    Arm/Group Description Subjects will receive a sugar pill (placebo) during their first sleep study night and will receive a pill of trazodone (100 mg) during their second sleep study night. Subjects will receive a pill of trazodone (100 mg) during their first sleep study night and will receive a sugar pill (placebo) during their second sleep study night.
    Period Title: First Intervention
    STARTED 8 7
    COMPLETED 8 7
    NOT COMPLETED 0 0
    Period Title: First Intervention
    STARTED 8 7
    COMPLETED 8 7
    NOT COMPLETED 0 0
    Period Title: First Intervention
    STARTED 8 7
    COMPLETED 8 7
    NOT COMPLETED 0 0

    Baseline Characteristics

    Arm/Group Title Placebo First Trazodone First Total
    Arm/Group Description Subjects will receive a sugar pill during their placebo night sleep study. Placebo pill: Subjects will receive a sugar pill during the placebo arm Subjects will receive trazodone during their treatment night sleep study Trazodone: Subjects will receive trazodone during one of their treatment arm studies Total of all reporting groups
    Overall Participants 8 7 15
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    53
    (7)
    53
    (14)
    53
    (10)
    Gender (Count of Participants)
    Female
    4
    50%
    5
    71.4%
    9
    60%
    Male
    4
    50%
    2
    28.6%
    6
    40%
    Region of Enrollment (participants) [Number]
    United States
    8
    100%
    7
    100%
    15
    100%

    Outcome Measures

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

    Outcome Measure Data

    Analysis Population Description
    two subjects were excluded from analysis because of excessive number of artifacts
    Arm/Group Title Placebo Trazodone
    Arm/Group Description Subjects will receive a sugar pill during their placebo night sleep study. Placebo pill: Subjects will receive a sugar pill during the placebo arm Subjects will receive trazodone during their treatment night sleep study Trazodone: Subjects will receive trazodone during one of their treatment arm studies
    Measure Participants 13 13
    Mean (Standard Error) [events/hour]
    38.7
    (6.2)
    28.5
    (5.6)
    2. Secondary Outcome
    Title Arousal Threshold (cmH2O)
    Description 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.
    Time Frame Participants will be assessed on 2 nights over an average period of 2 weeks.

    Outcome Measure Data

    Analysis Population Description
    two subjects were excluded from analysis because of excessive number of artifacts
    Arm/Group Title Placebo Trazodone
    Arm/Group Description Subjects will receive a sugar pill during their placebo night sleep study. Placebo pill: Subjects will receive a sugar pill during the placebo arm Subjects will receive trazodone during their treatment night sleep study Trazodone: Subjects will receive trazodone during one of their treatment arm studies
    Measure Participants 13 13
    Mean (Standard Deviation) [cmH2O]
    -19.3
    (3.9)
    -20.3
    (3.7)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Trazodone
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.52
    Comments
    Method t-test, 2 sided
    Comments

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Placebo Trazodone
    Arm/Group Description Subjects will receive a sugar pill during their placebo night sleep study. Placebo pill: Subjects will receive a sugar pill during the placebo arm Subjects will receive trazodone during their treatment night sleep study Trazodone: Subjects will receive trazodone during one of their treatment arm studies
    All Cause Mortality
    Placebo Trazodone
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Placebo Trazodone
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/15 (0%) 0/15 (0%)
    Other (Not Including Serious) Adverse Events
    Placebo Trazodone
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/15 (0%) 0/15 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title D. Andrew Wellman
    Organization Brigham and women's Hospital
    Phone 617-732-8483
    Email awellman@rics.bwh.harvard.edu
    Responsible Party:
    David Andrew Wellman, Principal Investigator, Brigham and Women's Hospital
    ClinicalTrials.gov Identifier:
    NCT01817907
    Other Study ID Numbers:
    • BWH-2009P001862
    • P01HL095491-01A1
    First Posted:
    Mar 26, 2013
    Last Update Posted:
    Feb 24, 2017
    Last Verified:
    Jan 1, 2017