Effect of Desipramine on Genioglossus Muscle Activity in Healthy Adults Study A

NCT02428478 | Completed Phase 2 Results

• 1 other identifier: BWH-2014P001033A
• Study Type: interventional
• Target: 17
• 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 genioglossus muscle activity (EMG GG) during sleep in healthy control participants.

Conditions

Sleep Apnea, Obstructive

Outcome Measures

Primary Outcomes (1)

• Genioglossus Activity During Non-rapid Eye Movement (NREM) Sleep Measured as Percent of Wakefulness Activity

  Electromyography (EMG) was used to analyze genioglossus (GG) \[EMG GG\] muscle movement. EMG GG activity was recorded via standard needle electrodes inserted into the genioglossus (tongue) muscle. 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). Sleep values were then expressed as %wakefulness value for tonic and phasic EMG GG activity. Tonic activity was defined as the lowest EMG GG value during expiration, phasic activity was calculated as the peak value during inspiration minus the tonic value.

  1 night

Secondary Outcomes (1)

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

  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

ACTIVE COMPARATOR

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 - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy control subjects

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

Related Publications (1)

• Taranto-Montemurro L, Edwards BA, Sands SA, Marques M, Eckert DJ, White DP, Wellman A. Desipramine Increases Genioglossus Activity and Reduces Upper Airway Collapsibility during Non-REM Sleep in Healthy Subjects. Am J Respir Crit Care Med. 2016 Oct 1;194(7):878-885. doi: 10.1164/rccm.201511-2172OC.

  PMID: 26967681 DERIVED

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: Director, Sleep Disordered Breathing Lab, Brigham and Women's Hospital

Study Record Dates

• First Submitted: April 21, 2015
• First Posted: April 28, 2015
• Study Start: March 1, 2015
• Primary Completion: November 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)