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

Johns Hopkins University

Status and phase: Enrolling; Phase 2

Conditions: AMCI - Amnestic Mild Cognitive Impairment; Sleep Disturbance

Treatments: Drug: Trazodone; Drug: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05282550

R01AG071522 (U.S. NIH Grant/Contract)

IRB00301426

Details and patient eligibility

About

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).

Full 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.

Enrollment: 100 estimated patients

Sex: All

Ages: 55+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

---

100 participants in 2 patient groups, including a placebo group

Trazodone First

Active Comparator group

Description:

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

Treatment:

Drug: Placebo

Drug: Trazodone

Placebo First

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

Drug: Trazodone