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

NCT ID: NCT05282550

Last Updated: 2025-09-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-02-02
• Study Completion Date: 2028-06-30

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).

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.

Conditions

AMCI - Amnestic Mild Cognitive Impairment; Sleep Disturbance

Study Design

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

Study Groups

Trazodone First

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

Group Type: ACTIVE_COMPARATOR

Trazodone

Intervention Type: DRUG

50mg of trazodone administered for 4 weeks.

Placebo

Intervention Type: DRUG

Placebo administered for 4 weeks.

Placebo First

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

Group Type: PLACEBO_COMPARATOR

Trazodone

Intervention Type: DRUG

50mg of trazodone administered for 4 weeks.

Placebo

Intervention Type: DRUG

Placebo administered for 4 weeks.

Interventions

Trazodone

50mg of trazodone administered for 4 weeks.

Intervention Type: DRUG

Placebo

Placebo administered for 4 weeks.

Intervention Type: DRUG

Other Intervention Names

Desyrel

Eligibility Criteria

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)

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

• Minimum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Aging (NIA)

NIH

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Barry Greenberg, PhD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Johns Hopkins Hospital

Baltimore, Maryland, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Barry Greenberg, PhD

Role: CONTACT

bgreen45@jhmi.edu

410-955-1696

Paul Rosenberg, MD

Role: CONTACT

prosenb9@jhmi.edu

410-550-9883

Facility Contacts

Barry Greenberg, PhD

Role: primary

bgreen45@jhmi.edu

410-955-1696

Paul Rosenberg, MD

Role: backup

prosenb9@jhmi.edu

410-550-9883

Other Identifiers

R01AG071522

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB00301426

Identifier Type: -

Identifier Source: org_study_id