Tiagabine to Enhance Slow Wave Sleep in Patients With Sleep Apnea (TESSA)

Inducing Slow Wave Sleep to Treat Obstructive Sleep Apnea

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.

Study Overview

• Status: Completed
• Conditions: Sleep Apnea, Obstructive
• Intervention / Treatment: Drug: Placebo; Drug: Tiagabine

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).

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Sleep Disorders Research Program Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

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

Exclusion Criteria:

• History of seizures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Tiagabine; Tiagabine PO 12 mg before sleep	Drug: Tiagabine; GABA reuptake inhibitor; Other Names: Gabitril
PLACEBO_COMPARATOR: Placebo; Placebo PO before sleep	Drug: Placebo; Placebo comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Apnea Hypopnea Index (AHI)	Number of apneas + hypopneas per hour of sleep. Hypopnea criteria: reduction in 30% of baseline flow plus 3% desaturation or arousal.	1 night

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Slow Wave Sleep (% Total Sleep Time)	Fraction of sleep spent in stage N3	1 night
Arousal Threshold (Esophageal Pressure Swing)	The arousal threshold was quantified as the mean of all the nadir negative esophageal pressure swings immediately preceding an arousal at the end of an obstructive apnea or hypopnea during both placebo and tiagabine nights.	1 night

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (ACTUAL): June 1, 2016
• Study Completion (ACTUAL): July 1, 2016

Study Registration Dates

• First Submitted: March 9, 2015
• First Submitted That Met QC Criteria: March 12, 2015
• First Posted (ESTIMATE): March 13, 2015

Study Record Updates

• Last Update Posted (ACTUAL): August 15, 2017
• Last Update Submitted That Met QC Criteria: July 14, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: phenotype; slow wave sleep; tiagabine; arousal threshold
• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Apnea; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; GABA Agents; Anticonvulsants; GABA Uptake Inhibitors; Tiagabine
• Other Study ID Numbers: BWH-2012P000956B