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

NCT02436031 | Completed Phase 2 Results

• 1 other identifier: BWH-2014P001033B
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Sleep Apnea, Obstructive

Outcome Measures

Primary Outcomes (1)

• Change in Pharyngeal Critical Collapsing Pressure (Pcrit) as a Measure of Upper Airway Collapsibility

  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.

  1 night

Secondary Outcomes (2)

• Genioglossus Muscle Responsiveness to Progressively Greater Epiglottic Pressure Swings

  1 night

• Number of Apnoea-Hypopnea Index (AHI) Events During Non-Random Eye Movement (NREM) Sleep

  1 night

Study Arms (2)

Desipramine First, Placebo Second

ACTIVE COMPARATOR

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; Drug: Placebo

Placebo First, Desipramine Second

EXPERIMENTAL

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; Drug: Placebo

Interventions

Desipramine DRUG

200 mg administered 2 hours before normal sleep time

Also known as: Norpramine

Desipramine First, Placebo Second; Placebo First, Desipramine Second

Placebo DRUG

Placebo-matching desipramine administered 2 hours before normal sleep time

Desipramine First, Placebo Second; Placebo First, Desipramine Second

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Cardiovascular disease other than well controlled hypertension
• Depression

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (1)

Sleep Disorders Research Program Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Sleep Apnea, Obstructive

Interventions

Desipramine

Condition Hierarchy (Ancestors)

Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Andrew Wellman, MD, PhD
• Organization: Brigham and Women's Hospital

awellman@rics.bwh.harvard.edu

Study Officials

• Andrew Wellman, MD PhD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine, Harvard Medical School | Director, Sleep Disordered Breathing Lab

Study Record Dates

• First Submitted: May 1, 2015
• First Posted: May 6, 2015
• Study Start: April 1, 2015
• Primary Completion: December 1, 2015
• Study Completion: March 1, 2016
• Last Updated: March 30, 2017
• Results First Posted: March 30, 2017

Record last verified: 2017-02

Locations

US (1)