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NCT Number: NCT02436031

Effect of Desipramine on Upper Airway Collapsibility and Genioglossus Muscle Activity in Patients With Obstructive Sleep Apnea - Study B

Obstructive sleep apnea (OSA) is common and has major health implications but treatment options are limited. OSA patients show a marked reduction in upper airway (UA) dilator muscle activity at sleep onset and this phenomenon leads to increased collapsibility of UA compared to normal participants. Until recently, the search for medicines to activate pharyngeal muscles in sleeping humans has been discouraging. However, exciting new animal research has shown that drugs with noradrenergic and antimuscarinic effects can restore pharyngeal muscle activity to waking levels. In this protocol the investigators will test the effect of desipramine (a tricyclic antidepressant with strong noradrenergic and antimuscarinic effects) on upper airway collapsibility and genioglossus muscle activity (EMG GG) during sleep in OSA patients.

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Key information

Conditions

Sleep Apnea, Obstructive Apnea Dyssomnias Nervous System Diseases Respiration Disorders Respiratory Tract Diseases Sleep Apnea Syndromes Sleep Disorders, Intrinsic Sleep Wake Disorders

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Sleep Disorders Research Program Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

About this study

Two overnight sleep studies, a placebo night and a drug night, will be performed approximately one week apart in random order. The placebo or drug will be administered 2 hours before lights out. At least 15 minutes of quiet wakefulness will be recorded to quantify the participant's EMG GG activity while awake and at sleep onset (alpha-theta transition at the electroencephalogram).

During the second part of the night, the participants will be connected to a modified continuous positive airway pressure (CPAP) machine (Pcrit3000, Respironics) which can provide a wide range of pressures between 20 and -20 cmH2O in order to modify upper airway pressure and measure pharyngeal critical collapsing pressure (Pcrit), ventilation at 0 cmH2O when UA muscle are passive and active as well as change in EMG GG as a function of epiglottic pressure (muscle responsiveness).

Apnea-hypopnea index (AHI) will be calculated in each night from the part of the study off CPAP.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Diagnosed OSA (moderate-to-severe; apnea hypopnea index >15 events/hr)

Exclusion criteria

  • Cardiovascular disease other than well controlled hypertension
  • Depression

Treatment and study plan

Desipramine

Drug

200 mg administered 2 hours before normal sleep time

Other names: Norpramine

Placebo

Drug

Placebo-matching desipramine administered 2 hours before normal sleep time

Primary outcomes

  1. Change in Pharyngeal Critical Collapsing Pressure (Pcrit) as a Measure of Upper Airway Collapsibility

    Time frame: 1 night

    Participants were connected to a modified continuous positive airway pressure (CPAP) machine (Pcrit3000, Respironics) which provided a wide range of pressures between 20 and -20 cm H2O in order to modify upper airway pressure. Following a baseline recording period of 5 minutes, the CPAP level was reduced to varying suboptimal pressures. Change in Pcrit was used to determine the collapsibility of the upper airway under both passive and active conditions, and is expressed as Passive Pcrit: ventilation at a nasal pressure of 0 cm H2O when pharyngeal muscles are passive; Active Pcrit: ventilation at a nasal pressure of 0 cm H2O when pharyngeal muscles are active. Improved=more negative Pcrit.

Secondary outcomes

  1. Genioglossus Muscle Responsiveness to Progressively Greater Epiglottic Pressure Swings

    Time frame: 1 night

    Electromyography (EMG) was used to analyze genioglossus (GG) [EMG GG] muscle activity. EMG GG activity was recorded via standard needle electrodes inserted into the genioglossus muscle (tongue). Activity of EMG GG was measured during wakefulness and sleep as % of maximum activation obtained pushing the tongue against closed teeth during wakefulness (GG%max). Participants were connected to a modified continuous positive airway pressure (CPAP) machine (Pcrit3000, Respironics) which provided a wide range of pressures between 20 and -20 cm H2O in order to modify upper airway pressure and measure change in EMG GG as a function of epiglottic pressure (muscle responsiveness) (%max/cmH2O).

  2. Number of Apnoea-Hypopnea Index (AHI) Events During Non-Random Eye Movement (NREM) Sleep

    Time frame: 1 night

    The AHI is the number of apneas (pauses in breathing) or hypopneas (shallow breathing) recorded during the study per hour of sleep. Data for the calculation of the AHI was collected while the participant was in NREM sleep in the supine position and off CPAP (breathing spontaneously).

Sponsors and collaborators

Lead sponsor

Brigham and Women's Hospital

Other

Registry information

Official study title

The Effect of Desipramine on Upper Airway Collapsibility and Genioglossus Muscle Activity During Sleep in Patients With Obstructive Sleep Apnea - Study B

Acronym: DESOSA

Important dates

Study start
2015
Primary completion
2015
Study completion
2016
First posted
May 6, 2015
Registry last updated
Mar 30, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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