Effect of Desipramine on Upper Airway Collapsibility and Genioglossus Muscle Activity in Patients With Obstructive Sleep Apnea - Study B
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Insomnia Sleep Studies, Pulmonary, Pulmonary |
| Therapuetic Areas: | Psychiatry / Psychology, Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | 18 - 60 |
| Updated: | 4/21/2016 |
| Start Date: | April 2015 |
| End Date: | June 2016 |
The Effect of Desipramine on Upper Airway Collapsibility and Genioglossus Muscle Activity During Sleep in Patients With Obstructive Sleep Apnea - Study B
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.
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.
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.
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.
Inclusion Criteria:
- Diagnosed OSA (moderate-to-severe; apnea hypopnea index >15 events/hr)
Exclusion Criteria:
- Cardiovascular disease other than well controlled hypertension
- Depression
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