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

NCT ID: NCT02428478

Last Updated: 2017-03-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-03-31
• Study Completion Date: 2016-03-31

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).

Conditions

Sleep Apnea, Obstructive

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Desipramine First, Placebo Second

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.

Group Type: ACTIVE_COMPARATOR

Desipramine

Intervention Type: DRUG

200 mg administered 2 hours before normal sleep time

Placebo

Intervention Type: DRUG

Placebo-matching desipramine administered 2 hours before normal sleep time

Placebo First, Desipramine Second

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.

Group Type: ACTIVE_COMPARATOR

Desipramine

Intervention Type: DRUG

200 mg administered 2 hours before normal sleep time

Placebo

Intervention Type: DRUG

Placebo-matching desipramine administered 2 hours before normal sleep time

Interventions

Desipramine

200 mg administered 2 hours before normal sleep time

Intervention Type: DRUG

Placebo

Placebo-matching desipramine administered 2 hours before normal sleep time

Intervention Type: DRUG

Other Intervention Names

Norpramine

Eligibility Criteria

Inclusion Criteria

• Healthy control subjects

Exclusion Criteria

• Cardiovascular disease other than well controlled hypertension
• Depression

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

David Andrew Wellman

Director, Sleep Disordered Breathing Lab, Brigham and Women's Hospital

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Andrew Wellman, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

Sleep Disorders Research Program Brigham and Women's Hospital

Boston, Massachusetts, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 26967681 (View on PubMed)

Other Identifiers

BWH-2014P001033A

Identifier Type: -

Identifier Source: org_study_id