Targeting Cognition in Early Alzheimer's Disease by Improving Sleep With Trazodone

NCT05282550 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: IRB00301426R01AG071522
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

To investigate the effect of trazodone on sleep, hippocampal-dependent memory and hippocampal excitability. The investigators hypothesize that trazodone will improve total sleep time and proportion of time in Slow Wave Sleep (SWS).

Conditions

AMCI - Amnestic Mild Cognitive Impairment; Sleep Disturbance

Keywords

AMCI; Slow wave sleep; Trazodone; Cognition

Outcome Measures

Primary Outcomes (7)

• Change in total sleep duration between the treatment arms

  Comparison of means of total sleep duration from baseline measured in minutes between trazodone and placebo arm.

  Baseline and End of study, up to 12 weeks

• Change in Slow Wave Sleep (SWS) duration between the treatment arms

  Comparison of means of SWS from baseline measured in minutes between trazodone and placebo arm.

  Baseline and End of study, up to 12 weeks

• Change in SWS intensity between the treatment arms

  Comparison of means of SWS intensity measured from baseline in volts squared between trazodone and placebo arm.

  Baseline and End of study, up to 12 weeks

• Change in sleep onset latency between the treatment arms

  Comparison of means of sleep onset latency from baseline measured in minutes between trazodone and placebo arm.

  Baseline and End of study, up to 12 weeks

• Change in sleep fragmentation between the treatment arms

  Comparison of means of sleep fragmentation from baseline measured in minutes between trazodone and placebo arm.

  Baseline and End of study, up to 12 weeks

• Change in self reported sleep measure Pittsburgh Sleep Quality Index (PSQI) between treatment arms

  Comparison of means score for PSQI from baseline between trazodone and placebo arm. A higher score means a worse outcome.

  Baseline and End of study, up to 12 weeks

• Change in self reported sleep measure Epworth Sleepiness Score (ESS) between treatment arms

  Comparison of means score for ESS from baseline between trazodone and placebo arm. A higher score means a worse outcome.

  Baseline and End of study, up to 12 weeks

Secondary Outcomes (2)

• Change in memory performance between treatment arms

  Baseline and End of study, up to 12 weeks

• Change in hippocampal activation on Function Magnetic Resonance Imaging (fMRI) measures during memory functioning between treatment arms

  Baseline and End of study, up to 12 weeks

Study Arms (2)

Trazodone First

ACTIVE COMPARATOR

Trazodone (50 mg at bedtime) and then placebo after a 4-week washout period.

Drug: Trazodone; Drug: Placebo

Placebo First

PLACEBO COMPARATOR

Placebo and then Trazodone (50 mg at bedtime) after a 4-week washout period.

Drug: Trazodone; Drug: Placebo

Interventions

Trazodone DRUG

50mg of trazodone administered for 4 weeks.

Also known as: Desyrel

Placebo First; Trazodone First

Placebo DRUG

Placebo administered for 4 weeks.

Placebo First; Trazodone First

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Mild Cognitive Impairment (MCI) as defined by Albert et al.2 including subjective memory complaint and/or objective evidence of memory problems;
• Clinical Dementia Rating (CDR) of 0.5 with a Memory Box score of \>=0.5;
• Evidence of sleep complaints with Pittsburgh Sleep Quality Index score of \>5 (a well-validated cutoff observed in \>40% of older persons);
• Memory performance \> 1.5 Standard Deviation (SD) below age-and education-matched control subjects on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) List Recall;
• Visual and auditory acuity adequate for neuropsychological testing;
• Good general health with no disease expected to interfere with the study;
• Able to have Magnetic Resonance Imaging (MRI) scan;
• Availability of knowledgeable informant (KI)

You may not qualify if:

• Less than 55 years of age to reduce likelihood of including individuals with frontotemporal dementia or non-dementia MCI;
• Too frail or medically unstable to undergo study procedures;
• Prior diagnosis of Obstructive Sleep Apnea (OSA) or evidence of moderate-to-severe OSA on baseline Home Sleep Test (HST) as evidenced by an apnea/hypopnea index of \>15;
• Dementia;
• Cognitive complaints and deficits better explained by other medical/neurologic conditions;
• Delirium;
• Allergic to trazodone;
• Taking sleep medications including trazodone;
• Current substance abuse;
• Current major depressive, manic, or acute psychotic episode;
• Prior diagnosis of significant systemic illness or unstable medical condition which could lead to difficulty complying with the study protocol or represent alternate primary cause of memory problems beyond Alzheimer's Disease (AD) pathology:
• Lack of available KI;
• Prior diagnosis of Q wave T wave Corrected for heart rate (QTc) \> 470 msec (females) or \> 450 msec (males);
• Inability to provide informed consent

Sponsors & Collaborators

• Johns Hopkins University: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Johns Hopkins Hospital

Baltimore, Maryland, 21205, United States

RECRUITING

MeSH Terms

Conditions

Parasomnias

Interventions

Trazodone

Condition Hierarchy (Ancestors)

Sleep Wake Disorders; Nervous System Diseases; Mental Disorders

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyridones; Pyridines

Study Officials

• Barry Greenberg, PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Barry Greenberg, PhD

CONTACT

410-955-1696; bgreen45@jhmi.edu

Paul Rosenberg, MD

CONTACT

410-550-9883; prosenb9@jhmi.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Study drug will be compounded by the Investigational Drug Service (IDS) at Johns Hopkins Bayview Medical Center. The IDS will prepare blind medication using opaque capsules and randomly assign eligible participants to treatment order (ie, starting with trazodone vs. placebo treatment).
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: We will administer trazodone and placebo for 4 weeks each with a 4-week washout.

Study Record Dates

• First Submitted: March 8, 2022
• First Posted: March 16, 2022
• Study Start: February 2, 2023
• Primary Completion (Estimated): July 30, 2027
• Study Completion (Estimated): June 30, 2028
• Last Updated: September 18, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 1 year after study completion
• Access Criteria: Upon approval of data analytic strategy by study team

Locations

US (1)