TrazoDose: Trazodone Dose Tolerance and APAP Adherence

Sponsor

Louis Stokes VA Medical Center (U.S. Fed)

Overall Status

Suspended

CT.gov ID

NCT02945644

Collaborator

(none)

Enrollment

Location

Arms

45.6

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Sleep Apnea, Obstructive	Drug: Trazodone Drug: Placebo	Phase 1

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

45 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Randomized Controlled Trial of Trazodone Dose Tolerance and APAP Adherence

Actual Study Start Date :

Feb 13, 2017

Anticipated Primary Completion Date :

Sep 1, 2020

Anticipated Study Completion Date :

Dec 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo pill filled with inert material	Drug: Placebo take at bedtime for 14 days
Active Comparator: Trazodone 50mg	Drug: Trazodone take at bedtime for 14 days Other Names: oleptro Desyrel
Active Comparator: Trazodone 100mg	Drug: Trazodone take at bedtime for 14 days Other Names: oleptro Desyrel

Arm

Intervention/Treatment

Placebo Comparator: Placebo

pill filled with inert material

Drug: Placebo

take at bedtime for 14 days

Active Comparator: Trazodone 50mg

Drug: Trazodone

take at bedtime for 14 days

Other Names:

oleptro

Desyrel

Active Comparator: Trazodone 100mg

Drug: Trazodone

take at bedtime for 14 days

Other Names:

oleptro

Desyrel

Outcome Measures

Primary Outcome Measures

Discontinuation rate by participant [14-16 days post-randomization]
Did the participant discontinue trazodone at a higher rate than placebo?

Secondary Outcome Measures

3 month APAP adherence [3 months post-randomization assessing 30 days before this 3 month period]
APAP use in last 30 days (of the 3 month period) as measured by (1) average hours/day and (2) percent days with 4 or more hours use
Respiratory patterning [14-16 days post-randomization]
Variation of breath to breath tidal volume obtained from plethysmography (a stretchy band around the chest x 20 minutes while wearing APAP)
Medication Satisfaction [14-16 days post-randomization]
Treatment Satisfaction Questionnaire for Medications version II overall and subscale scores
side-effect profile [14-16 days post-randomization]
participant-reported side effects of study drug
sleepiness [14-16 days post-randomization]
Epworth Sleepiness Scale
insomnia [14-16 days post-randomization]
Insomnia Severity Index
general self-efficacy [14-16 days post-randomization]
General Self-Efficacy Scale
depression [14-16 days post-randomization]
Clinically Useful Depression Outcome Scale (CUDOS)
anxiety [14-16 days post-randomization]
Clinically Useful Anxiety Outcome Scale (CUXOS)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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