Trazodone Dose Tolerance and APAP Adherence

NCT ID: NCT02945644

Last Updated: 2020-05-11

Basic Information

• Recruitment Status: SUSPENDED
• Clinical Phase: PHASE1
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-02-13
• Study Completion Date: 2020-12-31

Brief Summary

Trazodone may help obstructive sleep apnea patients to stick to their therapy, but optimal dosing is unknown. This study looks at what dose of trazodone has the best balance of potential benefits to side-effects in people with obstructive sleep apnea who are either starting on positive airway pressure therapy or not adherent to it. Participants will be randomly assigned to one of three groups: trazodone 50 mg, trazodone 100 mg, or placebo for 14 days. The investigators will monitor side-effects and adherence to positive airway pressure therapy.

Detailed Description

Clinical Significance: Trazodone is an often-used medication in clinical sleep medicine. However, there is a dearth of information on side-effects with doses typically used for sleep. In addition, a significant proportion of the VA population have obstructive sleep apnea for which the primary treatment is positive airway therapy. However, many patients have difficulty adhering to this treatment long-term. Increased adherence to this modality has been shown to improve risk for cardiovascular and neurologic co-morbidity associated with obstructive sleep apnea. This project explores both the tolerability and safety of common doses of trazodone used in clinical sleep practice as well explores potential effects on positive airway pressure therapy adherence.

Objectives: This project seeks to determine the tolerability and multi-domain effect on sleep and mood of a 14 day course of trazodone at either 50 mg or 100 mg or placebo.

Research Plan: This is a three-group, randomized, double-blind, placebo-controlled trial with prospective data collection of VA outpatient sleep clinic patients with obstructive sleep apnea with who are non-adherent or newly started on auto-titrating positive airway pressure therapy. Evaluation focuses on medication tolerability as measured by number of days before study drug discontinuation by the participant, the Treatment Satisfaction Questionnaire for Medication, the side-effect profile at the two doses (50mg and 100mg) compared to placebo as well as longitudinal collection of adherence data and standardized questionnaires on sleepiness, insomnia, depression, anxiety, and self-efficacy. The investigators also plan to longitudinally monitor coefficient of variation of breath-to-breath tidal volume, a measure of respiratory mechanics which may be affected by trazodone use. Study participants will have 2 visits at baseline and 2 weeks after randomization.

Methodology: This study will be conduced in the Louis Stokes Cleveland Medical Center - Wade Park Sleep Clinic, a tertiary institutional referral facility. Participants must be adults with obstructive sleep apnea prescribed auto-titrating positive airway therapy who are either newly initiated or do not fulfill standard criteria for adherence and do not have allergy to trazodone; current use of trazodone, monoamine oxidase inhibitors, or sedative hypnotics; alcohol or drug abuse; severe psychiatric disease; epilepsy; significant cardiac disease; liver disease; pregnancy; hypotension; or predisposition to priapism. Study staff will interview the potential participant and do a review of the medical record for exclusion criteria before consent is obtained. The investigators expect to recruit 45 participants into the study with a 20% attrition rate before completion. Hypothesis about the tolerability of trazodone and effect on positive airway therapy adherence was prespecified.

Conditions

Sleep Apnea, Obstructive

Study Design

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

Study Groups

Placebo

pill filled with inert material

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

take at bedtime for 14 days

Trazodone 50mg

Group Type: ACTIVE_COMPARATOR

Trazodone

Intervention Type: DRUG

take at bedtime for 14 days

Trazodone 100mg

Group Type: ACTIVE_COMPARATOR

Trazodone

Intervention Type: DRUG

take at bedtime for 14 days

Interventions

Trazodone

take at bedtime for 14 days

Intervention Type: DRUG

Placebo

take at bedtime for 14 days

Intervention Type: DRUG

Other Intervention Names

oleptro; Desyrel

Eligibility Criteria

Inclusion Criteria

• Louis Stokes Cleveland VA Sleep Medicine clinic patient
• AHI greater than or equal to 5
• obstructive sleep apnea
• new initiation or nonadherence to APAP

Exclusion Criteria

• schizophrenia
• bipolar disorder
• current use of trazodone or sedative hypnotics
• allergy to trazodone
• current use of tricyclic antidepressants or monoamine oxidase inhibitors
• current alcohol or drug abuse
• heart failure
• heart attack in past 3 months
• congenital long QT, ventricular arrhythmia (including Torsades de Pointes), bradycardia, or digoxin therapy
• use of amiodarone, sotalol, dofetilide, or dronedarone
• epilepsy
• liver disease
• pregnancy (or planning pregnancy)
• right of priapism: history of priapism, sickle cell disease, Farby disease

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

Sponsors

Louis Stokes VA Medical Center

FED

Sponsor Role: lead

Responsible Party

Kingman Strohl

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kingman P Strohl, MD

Role: PRINCIPAL_INVESTIGATOR

Louis Stokes Cleveland VA Medical Center

Locations

Louis Stokes Cleveland VA Medical Center

Cleveland, Ohio, United States

Countries

United States

Other Identifiers

16025-H17

Identifier Type: -

Identifier Source: org_study_id