Trazodone on OSA Endotypes

Effect of Trazodone on Obstructive Sleep Apnea Endotypes and Severity

Obstructive sleep apnea (OSA) is common and has major health implications but treatment options are limited. Some OSA patients with low arousal threshold wake up prematurely during an obstructive event and do not have time for spontaneous upper airway (UA) dilator muscle recruitment. As a consequence they are exposed to apnea and hypopnea cycling. In this protocol the investigators will test the effect of trazodone administered before sleep on OSA traits and OSA severity during sleep.

Study Overview

• Status: Recruiting
• Conditions: Obstructive Sleep Apnea
• Intervention / Treatment: Drug: Placebo oral tablet; Drug: Trazodone Hydrochloride

Detailed Description

Two overnight home sleep studies will be performed: a drug night and a placebo night. The patient will breath spontaneously (without CPAP) for both nights. On the study nights, subjects be instrumented with a full polygraphy for monitoring sleep, and respiratory events. Trazodone 100 mg will be given 30 min before lights out. At least four hours of sleep with high quality signal acquisition will be required for a study to be judged adequate. After the first overnight study is completed, there will be a one-week washout period prior to crossing over to the other treatment.

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Ludovico Messineo; Phone Number: (617) 732-4013; Email: lmessineo@bwh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham and Women's Hospital
      • Contact: Nicole Calianese, BS; Phone Number: 617-732-8976; Email: ncalianese@mgb.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Moderate-to-severe OSA (AHI ≥ 15 events/hr)

Exclusion Criteria:

• All participants will be healthy and without major organ system disease that would preclude undergoing the physiological measurements.
• Use of medications expected to stimulate or depress respiration (including opioids, barbiturates, acetazolamide, doxapram, almitrine, theophylline, 4-hydroxybutanoic acid).
• Use of SNRIs/SSRIs.
• Conditions likely to affect OSA physiology: neuromuscular disease or other major neurological disorder, heart failure (also below), or any other unstable major medical condition.
• Sleep disordered breathing or respiratory disorders other than obstructive sleep apnea:
• Other sleep disorders: periodic limb movements (periodic limb movement arousal index > 10/hr), narcolepsy, or parasomnias.
• Hypersensitivity to the study drug (angioedema or urticaria)
• Contraindications to DAW2020
• Use of medications that lengthen QTc interval
• Hypokaliemia, hypomagnesemia, uncontrolled thyroid disease
• Severe claustrophobia.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo capsule 30 min before sleep	Drug: Placebo oral tablet; Placebo capsule taken 30 min before sleep
Experimental: Trazodone; Trazodone capsule 30 min before sleep	Drug: Trazodone Hydrochloride; Trazodone 100 mg 30 min before sleep

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of trazodone on arousal threshold (%eupnea)	Arousal threshold will be calculated non invasively from the home sleep test flow signal	1 night

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of trazodone on apnea hypopnea index (events/h)	Apnea hypopnea index will be calculated from the home sleep test	1 night

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: February 22, 2024
• First Submitted That Met QC Criteria: February 22, 2024
• First Posted (Actual): February 29, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 5, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Wake Disorders; Apnea; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Neurotransmitter Agents; Membrane Transport Modulators; Anti-Anxiety Agents; Tranquilizing Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Antidepressive Agents; Serotonin Agents; Selective Serotonin Reuptake Inhibitors; Antidepressive Agents, Second-Generation; Trazodone
• Other Study ID Numbers: 2020P002760-t

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No