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

Sleep Apnea, Obstructive Clinical Trial

— DESOSA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02436031
• Other study ID #: BWH-2014P001033B
• Status: Completed
• Phase: Phase 2
• First received: May 1, 2015
• Last updated: July 14, 2016
• Start date: April 2015
• Est. completion date: March 2016

Study information

• Verified date: July 2016
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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 subjects. 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.

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 subject's EMG GG activity while awake and at sleep onset (alpha-theta transition at the electroencephalogram).

During the second part of the night, the subjects 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 critical closing 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: March 2016
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

• Cardiovascular disease other than well controlled hypertension

• Depression

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Apnea
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive

Intervention

Drug:
• Desipramine
200 mg administered 2 hour before normal sleep time
• Placebo

Locations

Country	Name	City	State
United States	Sleep Disorders Research Program Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Brigham and Women's Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Collapsibility of the UA during sleep when the pharyngeal muscles are passive and active: Pcrit (cmH2O), Passive and Active V0 (L/min) genioglossus muscle responsiveness to increased UA resistance (GG%max/cmH2O).	Epiglottic pressure will be altered using a modified CPAP machine (Pcrit3000, Respironics) which can provide a range of pressure between 20 and -20 cmH2O For genioglossus muscle responsiveness, data will be expressed as change in GG EMG for cmH2O change in epiglottic pressure.; Pcrit: critical closing pressure. Passive V0: ventilation at a nasal pressure of 0 cmH2O when pharyngeal muscles are passive. Active V0 ventilation at a nasal pressure of 0 cmH2O when pharyngeal muscles are active	1 night	No
Secondary	Genioglossus activity at sleep onset (GG%wakefulness)	Activity of GG EMG will be measured during wakefulness and sleep onset (alpha-tetha transition) as % of maximum activation obtained pushing the tongue against closed teeth during wakefulness (GG%max). Sleep values will then be expressed as %wakefulness value.	1 night	No
Secondary	Apnea hypopnea index (AHI)	AHI will be calculated in drug and placebo night when patients are off CPAP	1 night	No