Recruiting
Phase 2

Trazodone

Sponsor:

Johns Hopkins University

Code:

NCT05282550

Conditions

AMCI - Amnestic Mild Cognitive Impairment

Sleep Disturbance

Eligibility Criteria

Sex: All

Age: 55+

Healthy Volunteers: Not accepted

Interventions

Trazodone

Placebo

Study Details

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

Study ID

NCT05282550

Start date

Feb 2, 2023

Status verified date

Jun, 2026

Completion date

Jun 30, 2028

Anticipated

Primary completion date

Jul 30, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 55+

Healthy Volunteers: Not accepted

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 Design

Enrollment

100 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: Trazodone First

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

placebo comparator: Placebo First

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

Interventions

Trazodone

50mg of trazodone administered for 4 weeks.

Placebo

Placebo administered for 4 weeks.

Primary outcome measure

  • Change in total sleep duration between the treatment arms [ Time Frame: 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 ]
  • Change in SWS intensity between the treatment arms [ Time Frame: 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 ]
  • Change in sleep fragmentation between the treatment arms [ Time Frame: 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 ]
  • Change in self reported sleep measure Epworth Sleepiness Score (ESS) between treatment arms [ Time Frame: Baseline and End of study, up to 12 weeks ]

Central Contacts and Locations

Central contacts

Locations

Johns Hopkins Hospital

Recruiting

Baltimore, Maryland, United States, 21205

Contacts

Principal Investigator:

Barry Greenberg, PhD

More Information

Sponsor

Johns Hopkins University

Last update posted

Jun 17, 2026

Last verified

Jun, 2026

Keywords

  • AMCI
  • Slow wave sleep
  • Trazodone
  • Cognition

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Johns Hopkins University on 2026-06-17.