Trial Outcomes & Findings for Effect of Desipramine on Upper Airway Collapsibility and Genioglossus Muscle Activity in Patients With Obstructive Sleep Apnea - Study B (NCT NCT02436031)

NCT ID: NCT02436031

Last Updated: 2017-03-30

Results Overview

Participants were connected to a modified continuous positive airway pressure (CPAP) machine (Pcrit3000, Respironics) which provided a wide range of pressures between 20 and -20 cm H2O in order to modify upper airway pressure. Following a baseline recording period of 5 minutes, the CPAP level was reduced to varying suboptimal pressures. Change in Pcrit was used to determine the collapsibility of the upper airway under both passive and active conditions, and is expressed as Passive Pcrit: ventilation at a nasal pressure of 0 cm H2O when pharyngeal muscles are passive; Active Pcrit: ventilation at a nasal pressure of 0 cm H2O when pharyngeal muscles are active. Improved=more negative Pcrit.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

16 participants

Primary outcome timeframe

1 night

Results posted on

2017-03-30

Participant Flow

Participant milestones

Participant milestones
Measure
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.
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.
First Study Night
STARTED
8
8
First Study Night
COMPLETED
8
8
First Study Night
NOT COMPLETED
0
0
Second Study Night
STARTED
7
8
Second Study Night
COMPLETED
7
8
Second Study Night
NOT COMPLETED
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
All Analyzed Participants
n=14 Participants
All participants who were randomized, completed both study nights, and were included in the analysis. 1 participant was excluded due to insufficient sleep time.
Age, Continuous
55 years
n=5 Participants
Sex: Female, Male
Female
4 Participants
n=5 Participants
Sex: Female, Male
Male
10 Participants
n=5 Participants

PRIMARY outcome

Timeframe: 1 night

Population: All participants who were randomized, completed both study nights, and were included in the analysis. 1 participant was excluded due to insufficient sleep time.

Participants were connected to a modified continuous positive airway pressure (CPAP) machine (Pcrit3000, Respironics) which provided a wide range of pressures between 20 and -20 cm H2O in order to modify upper airway pressure. Following a baseline recording period of 5 minutes, the CPAP level was reduced to varying suboptimal pressures. Change in Pcrit was used to determine the collapsibility of the upper airway under both passive and active conditions, and is expressed as Passive Pcrit: ventilation at a nasal pressure of 0 cm H2O when pharyngeal muscles are passive; Active Pcrit: ventilation at a nasal pressure of 0 cm H2O when pharyngeal muscles are active. Improved=more negative Pcrit.

Outcome measures

Outcome measures
Measure
Desipramine
n=14 Participants
Desipramine 200 mg administered 2 hours before normal sleep time on the first study night or second study night.
Placebo
n=14 Participants
Placebo-matching desipramine administered 2 hours before normal sleep time on the first study night or second study night.
Change in Pharyngeal Critical Collapsing Pressure (Pcrit) as a Measure of Upper Airway Collapsibility
Active Pcrit
-5.2 cm H2O
Interval -7.0 to -2.8
-1.9 cm H2O
Interval -3.3 to -0.7
Change in Pharyngeal Critical Collapsing Pressure (Pcrit) as a Measure of Upper Airway Collapsibility
Passive Pcrit
-2.2 cm H2O
Interval -3.2 to 0.2
-0.7 cm H2O
Interval -1.7 to -0.4

SECONDARY outcome

Timeframe: 1 night

Population: All participants who were randomized, completed both study nights, and were included in the analysis. 1 participant was excluded due to insufficient sleep time.

Electromyography (EMG) was used to analyze genioglossus (GG) \[EMG GG\] muscle activity. EMG GG activity was recorded via standard needle electrodes inserted into the genioglossus muscle (tongue). Activity of EMG GG was measured during wakefulness and sleep as % of maximum activation obtained pushing the tongue against closed teeth during wakefulness (GG%max). Participants were connected to a modified continuous positive airway pressure (CPAP) machine (Pcrit3000, Respironics) which provided 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) (%max/cmH2O).

Outcome measures

Outcome measures
Measure
Desipramine
n=14 Participants
Desipramine 200 mg administered 2 hours before normal sleep time on the first study night or second study night.
Placebo
n=14 Participants
Placebo-matching desipramine administered 2 hours before normal sleep time on the first study night or second study night.
Genioglossus Muscle Responsiveness to Progressively Greater Epiglottic Pressure Swings
-0.24 %max/cmH2O
Interval -0.5 to -0.2
-0.25 %max/cmH2O
Interval -0.4 to -0.1

SECONDARY outcome

Timeframe: 1 night

Population: All participants who were randomized, completed both study nights, and were included in the analysis. 1 participant was excluded due to insufficient sleep time.

The AHI is the number of apneas (pauses in breathing) or hypopneas (shallow breathing) recorded during the study per hour of sleep. Data for the calculation of the AHI was collected while the participant was in NREM sleep in the supine position and off CPAP (breathing spontaneously).

Outcome measures

Outcome measures
Measure
Desipramine
n=13 Participants
Desipramine 200 mg administered 2 hours before normal sleep time on the first study night or second study night.
Placebo
n=13 Participants
Placebo-matching desipramine administered 2 hours before normal sleep time on the first study night or second study night.
Number of Apnoea-Hypopnea Index (AHI) Events During Non-Random Eye Movement (NREM) Sleep
34.3 events per hour
Interval 14.7 to 62.0
42.0 events per hour
Interval 20.5 to 53.3

Adverse Events

Desipramine

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

Placebo

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Desipramine
n=16 participants at risk
Desipramine 200 mg administered 2 hours before normal sleep time on the first study night or second study night.
Placebo
n=15 participants at risk
Placebo-matching desipramine administered 2 hours before normal sleep time on the first study night or second study night.
Nervous system disorders
Dizziness
6.2%
1/16
All randomized participants who received at least one dose of desipramine or placebo.
0.00%
0/15
All randomized participants who received at least one dose of desipramine or placebo.

Additional Information

Andrew Wellman, MD, PhD

Brigham and Women's Hospital

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place