Improving sleep to enhance cognition in early Alzheimer's disease using trazodone

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

This study is testing if the sleep medication trazodone can help improve sleep and memory in people with early Alzheimer's disease who have trouble sleeping.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 55 Years and up
• Sex: All
• Sponsor: Johns Hopkins University (Academic / other)
• Locations: 1 site (Baltimore, Maryland)
• Trial ID: NCT05282550 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effects of trazodone on sleep quality and cognitive function in individuals with Amnestic Mild Cognitive Impairment (aMCI) who experience sleep disturbances. It is a randomized, placebo-controlled, double-blind crossover study involving 100 participants, where each participant will receive trazodone and placebo for four weeks each, separated by a four-week washout period. The primary focus is to determine if trazodone can increase total sleep time and enhance slow wave sleep, which may positively impact memory and cognitive performance.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 55 and older with Amnestic Mild Cognitive Impairment and sleep complaints.

Not a fit: Patients with significant frailty or other health conditions that could interfere with the study may not benefit.

Why it matters

Potential benefit: If successful, this study could lead to improved sleep and cognitive function in patients with early Alzheimer's disease.

How similar studies have performed: Other studies have shown promise in using sleep interventions to improve cognitive outcomes, but this specific approach with trazodone is relatively novel.

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

Where this trial is running

Baltimore, Maryland

• Johns Hopkins Hospital — Baltimore, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Barry Greenberg, PhD — Johns Hopkins University
• Study coordinator: Barry Greenberg, PhD

Conditions AMCI - Amnestic Mild Cognitive Impairment; Sleep Disturbance; AMCI; Slow wave sleep; Trazodone; Cognition