Effect of Desipramine on Genioglossus Muscle Activity in Healthy Adults Study A (DESOSA)

Mass General Brigham

Status and phase: Completed; Phase 2

Conditions: Sleep Apnea, Obstructive

Treatments: Drug: Desipramine; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT02428478

BWH-2014P001033A

Details and patient eligibility

About

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.

Full 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).

Enrollment: 17 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Healthy control subjects

Exclusion criteria

• Cardiovascular disease other than well controlled hypertension
• Depression

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

---

17 participants in 2 patient groups

Desipramine First, Placebo Second

Active Comparator group

Description:

Desipramine 200 mg administered 2 hours before normal sleep time on first study night, then a 1-week non-treatment period, then placebo-matching desipramine administered 2 hours before normal sleep time on second study night.

Treatment:

Drug: Placebo

Drug: Desipramine

Placebo First, Desipramine Second

Active Comparator group

Description:

Placebo-matching desipramine administered 2 hours before normal sleep time on first study night, then a 1-week non-treatment period, then desipramine administered 2 hours before normal sleep time on second study night.

Treatment:

Drug: Placebo

Drug: Desipramine