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

June 15, 2026 updated by: Johns Hopkins University

RCT Targeting Cognition in Early Alzheimer's Disease by Improving Sleep With Trazodone (REST)

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The REST trial is a randomized, placebo-controlled, double-blind crossover study of trazodone (50 mg at bedtime) in participants with Amnestic Mild Cognitive impairment (aMCI) and sleep complaints. The investigators will randomize 100 subjects and administer trazodone and placebo for 4 weeks each with a 4-week washout period in between. A 4-week washout period is more than sufficient due to trazodone's elimination half-life of 10-12 hours. The crossover design will facilitate recruitment and enable the use of the subjects as a control without requiring a parallel placebo arm.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
100

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21205
        • Recruiting
        • Johns Hopkins Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Barry Greenberg, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

55 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Mild Cognitive Impairment (MCI) as defined by Albert et al.2 including subjective memory complaint and/or objective evidence of memory problems;
  2. Clinical Dementia Rating (CDR) of 0.5 with a Memory Box score of >=0.5;
  3. Evidence of sleep complaints with Pittsburgh Sleep Quality Index score of >5 (a well-validated cutoff observed in >40% of older persons);
  4. 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;
  5. Visual and auditory acuity adequate for neuropsychological testing;
  6. Good general health with no disease expected to interfere with the study;
  7. Able to have Magnetic Resonance Imaging (MRI) scan;
  8. Availability of knowledgeable informant (KI)
  9. Buschke Selective Reminding Test or more standard deviations below age-education norms

Exclusion Criteria:

  1. Less than 55 years of age to reduce likelihood of including individuals with frontotemporal dementia or non-dementia MCI;
  2. Too frail or medically unstable to undergo study procedures;
  3. 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;
  4. Dementia;
  5. Cognitive complaints and deficits better explained by other medical/neurologic conditions;
  6. Delirium;
  7. Allergic to trazodone;
  8. Taking sleep medications including trazodone;
  9. Current substance abuse;
  10. Current major depressive, manic, or acute psychotic episode;
  11. 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:
  12. Lack of available KI;
  13. Prior diagnosis of Q wave T wave Corrected for heart rate (QTc) > 470 msec (females) or > 450 msec (males);
  14. Inability to provide informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Trazodone First
Trazodone (50 mg at bedtime) and then placebo after a 4-week washout period.
Drug: Trazodone
50mg of trazodone administered for 4 weeks.
Other Names:
  • Desyrel
Drug: Placebo
Placebo administered for 4 weeks.
Placebo Comparator: Placebo First
Placebo and then Trazodone (50 mg at bedtime) after a 4-week washout period.
Drug: Trazodone
50mg of trazodone administered for 4 weeks.
Other Names:
  • Desyrel
Drug: Placebo
Placebo administered for 4 weeks.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in total sleep duration between the treatment arms
Time Frame: Baseline and End of study, up to 12 weeks
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
Time Frame: Baseline and End of study, up to 12 weeks
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
Time Frame: Baseline and End of study, up to 12 weeks
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
Time Frame: Baseline and End of study, up to 12 weeks
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
Time Frame: Baseline and End of study, up to 12 weeks
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
Time Frame: Baseline and End of study, up to 12 weeks
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
Time Frame: Baseline and End of study, up to 12 weeks
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in memory performance between treatment arms
Time Frame: Baseline and End of study, up to 12 weeks
Comparison of means for memory performance from baseline measured in percent correct between trazodone and placebo arm.
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
Time Frame: Baseline and End of study, up to 12 weeks
Comparison of means of hippocampal activation on fMRI measures calculated as a beta weight reflecting relative activation during memory functioning from baseline between trazodone and placebo arm. Higher activation suggests a worse outcome.
Baseline and End of study, up to 12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Johns Hopkins University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute on Aging (NIA)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Barry Greenberg, PhD, Johns Hopkins University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 2, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 30, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 30, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 8, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 8, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 16, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 17, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 15, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB00301426
  • R01AG071522 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The Executive Committee of the study, consisting of the study PIs and the Director of the Data Coordinating Center for this study will oversee the deidentified Individual Participant Data (IPD) sharing. This will include the review of requests for trial data and samples. The Executive Committee will assure that all investigators who receive data and/or specimens are qualified investigators, with research goals consistent with those stated in the consent form. A Material Transfer Agreement (MTA) and/or Data Use Agreement (DUA) will be in place with approved requestors before any transfer of bio-samples or data. Investigators receiving the data and/or samples will be required to cite the grant in any publications generated by the data and to send a copy of all publications to the study team.

IPD Sharing Time Frame

1 year after study completion

IPD Sharing Access Criteria

Upon approval of data analytic strategy by study team

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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