Tiagabine to Enhance Slow Wave Sleep in Patients With Sleep Apnea

Sleep Apnea, Obstructive Clinical Trial

— TESSA  

Official title:

Inducing Slow Wave Sleep to Treat Obstructive Sleep Apnea

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02387710
• Other study ID #: BWH-2012P000956B
• Status: Completed
• Phase: Phase 2
• First received: March 9, 2015
• Last updated: July 14, 2016
• Start date: March 2015
• Est. completion date: July 2016

Study information

• Verified date: July 2016
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Obstructive sleep apnea (OSA) is common and has major health implications but treatment options are limited. Interestingly, the severity of OSA is profoundly reduced in deep sleep (called "slow wave sleep"), potentially via an increase in the stimulus required to arouse from sleep. Here the investigators test the idea that the medication called "tiagabine" improves slow wave sleep and reduces OSA severity. The investigators will also test whether tiagabine raises the arousal threshold (more negative esophageal pressure), and whether detailed OSA "phenotyping" characteristics can predict the improvement in OSA severity with this intervention.

Description:

The current study tests the primary hypothesis that tiagabine improves sleep apnea severity in patients with moderate-to-severe sleep apnea (apnea hypopnea index measured in supine non-REM sleep; hypopneas defined by 3% desaturation or arousal). The investigators test three secondary hypotheses that tiagabine:

1. increases the proportion of total sleep time in slow wave sleep

2. raises the non-REM arousal threshold (more negative esophageal pressure) via (1).

3. is preferentially effective in patients whose OSA phenotype predicts that an increase in the arousal threshold is sufficient to resolve OSA versus those without such favorable physiology. Favorable physiology is defined here as having a low ventilatory drive at which stable breathing is theoretically feasible ("stable Vdrive" is <100% above eupneic ventilatory drive) due to any combination of a "high" upper airway muscle response, "good" passive anatomy (high Vpassive), and "low" steady-state loop gain (see Owens RL et al SLEEP 2014; Wellman A et al J Appl Physiol 2011, 2013; Eckert DJ et al 2013 AJRCCM).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: July 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 79 Years

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

• History of seizures

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Apnea
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive

Intervention

Drug:
• Tiagabine
GABA reuptake inhibitor
• Placebo
Placebo comparator

Locations

Country	Name	City	State
United States	Sleep Disorders Research Program Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Brigham and Women's Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	change in apnea hypopnea index (hypopnea criteria: 3% desaturation or arousal)		1 night	No
Secondary	change in slow wave sleep (% total sleep time)		1 night	No
Secondary	increase in arousal threshold (esophageal pressure swing)		1 night	No