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Trial record 6 of 47 for:    DESIPRAMINE

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

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ClinicalTrials.gov Identifier: NCT02436031
Recruitment Status : Completed
First Posted : May 6, 2015
Results First Posted : March 30, 2017
Last Update Posted : March 30, 2017
Sponsor:
Information provided by (Responsible Party):
David Andrew Wellman, Brigham and Women's Hospital

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.

Condition or disease Intervention/treatment Phase
Sleep Apnea, Obstructive Drug: Desipramine Drug: Placebo Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: The Effect of Desipramine on Upper Airway Collapsibility and Genioglossus Muscle Activity During Sleep in Patients With Obstructive Sleep Apnea - Study B
Actual Study Start Date : April 2015
Actual Primary Completion Date : December 2015
Actual Study Completion Date : March 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sleep Apnea

Arm Intervention/treatment
Active Comparator: 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.
Drug: Desipramine
200 mg administered 2 hours before normal sleep time
Other Name: Norpramine

Drug: Placebo
Placebo-matching desipramine administered 2 hours before normal sleep time

Experimental: 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.
Drug: Desipramine
200 mg administered 2 hours before normal sleep time
Other Name: Norpramine

Drug: Placebo
Placebo-matching desipramine administered 2 hours before normal sleep time




Primary Outcome Measures :
  1. Change in Pharyngeal Critical Collapsing Pressure (Pcrit) as a Measure of Upper Airway Collapsibility [ Time Frame: 1 night ]
    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.


Secondary Outcome Measures :
  1. Genioglossus Muscle Responsiveness to Progressively Greater Epiglottic Pressure Swings [ Time Frame: 1 night ]
    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).

  2. Number of Apnoea-Hypopnea Index (AHI) Events During Non-Random Eye Movement (NREM) Sleep [ Time Frame: 1 night ]
    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).



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • Cardiovascular disease other than well controlled hypertension
  • Depression

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02436031


Locations
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United States, Massachusetts
Sleep Disorders Research Program Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Brigham and Women's Hospital
Investigators
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Principal Investigator: Andrew Wellman, MD PhD Brigham and Women's Hospital

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Responsible Party: David Andrew Wellman, Assistant Professor of Medicine, Harvard Medical School | Director, Sleep Disordered Breathing Lab, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT02436031     History of Changes
Other Study ID Numbers: BWH-2014P001033B
First Posted: May 6, 2015    Key Record Dates
Results First Posted: March 30, 2017
Last Update Posted: March 30, 2017
Last Verified: February 2017
Additional relevant MeSH terms:
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Desipramine
Apnea
Sleep Apnea Syndromes
Sleep Apnea, Obstructive
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Nervous System Diseases
Antidepressive Agents, Tricyclic
Antidepressive Agents
Psychotropic Drugs
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Adrenergic Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Adrenergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs