Clinical trial NCT02428478: Effect of Desipramine on Genioglossus Muscle Activity in Healthy Adults Study A
Official title: The Effect of Desipramine on Genioglossus Muscle Activity During Sleep in Healthy Control Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sleep Apnea, Obstructive
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2015-04-28
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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 genioglossus muscle activity (EMG GG) during sleep in healthy control participants.

Detailed description: 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 awake EMG GG activity. Participants will then sleep in the lateral position to minimize pharyngeal resistance similar to previous studies of this kind.

The same will be done for stable non-rapid eye movement (NREM) and rapid eye movement (REM) sleep (free of arousals and other artifacts). Both NREM and REM sleep will be analyzed, recognizing that REM is less frequent on these drugs.

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 cm H2O in order to modify upper airway pressure and measure change in EMG GG as a function of epiglottic pressure (muscle responsiveness).

Eligibility criteria: Inclusion Criteria:

* Healthy control subjects

Exclusion Criteria:

* Cardiovascular disease other than well controlled hypertension
* Depression

Primary outcomes:
measure: Genioglossus Activity During Non-rapid Eye Movement (NREM) Sleep Measured as Percent of Wakefulness Activity
timeFrame: 1 night
Secondary outcomes:
measure: Change in Pharyngeal Critical Collapsing Pressure (Pcrit) as a Measure of Upper Airway Collapsibility
timeFrame: 1 night
Other outcomes:
Locations:
city: Boston
country: United States
facility: Sleep Disorders Research Program Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Andrew Wellman, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Taranto-Montemurro L, Edwards BA, Sands SA, Marques M, Eckert DJ, White DP, Wellman A. Desipramine Increases Genioglossus Activity and Reduces Upper Airway Collapsibility during Non-REM Sleep in Healthy Subjects. Am J Respir Crit Care Med. 2016 Oct 1;194(7):878-885. doi: 10.1164/rccm.201511-2172OC.