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

NCT ID: NCT02436031

Last Updated: 2017-03-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-30
• 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 upper airway collapsibility and genioglossus muscle activity (EMG GG) during sleep in OSA patients.

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 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.

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: EXPERIMENTAL

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

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

Exclusion Criteria

• Cardiovascular disease other than well controlled hypertension
• Depression

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

David Andrew Wellman

Assistant Professor of Medicine, Harvard Medical School | Director, Sleep Disordered Breathing Lab

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

Other Identifiers

BWH-2014P001033B

Identifier Type: -

Identifier Source: org_study_id