Tiagabine to Enhance Slow Wave Sleep in Patients With Sleep Apnea

NCT ID: NCT02387710

Last Updated: 2017-08-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-03-31
• Study Completion Date: 2016-07-31

Brief 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.

Detailed 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).

Conditions

Sleep Apnea, Obstructive

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Tiagabine

Tiagabine PO 12 mg before sleep

Group Type: ACTIVE_COMPARATOR

Tiagabine

Intervention Type: DRUG

GABA reuptake inhibitor

Placebo

Placebo PO before sleep

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo comparator

Interventions

Tiagabine

GABA reuptake inhibitor

Intervention Type: DRUG

Placebo

Placebo comparator

Intervention Type: DRUG

Other Intervention Names

Gabitril

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• History of seizures

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

David Andrew Wellman

Director, Sleep Disordered Breathing Laboratory

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Sleep Disorders Research Program Brigham and Women's Hospital

Boston, Massachusetts, United States

Countries

United States

References

Taranto-Montemurro L, Sands SA, Edwards BA, Azarbarzin A, Marques M, de Melo C, Eckert DJ, White DP, Wellman A. Effects of Tiagabine on Slow Wave Sleep and Arousal Threshold in Patients With Obstructive Sleep Apnea. Sleep. 2017 Feb 1;40(2):zsw047. doi: 10.1093/sleep/zsw047.

Reference Type: DERIVED

PMID: 28364504 (View on PubMed)

Other Identifiers

BWH-2012P000956B

Identifier Type: -

Identifier Source: org_study_id