Clinical trial NCT05282550: Targeting Cognition in Early Alzheimer's Disease by Improving Sleep With Trazodone
Official title: RCT Targeting Cognition in Early Alzheimer's Disease by Improving Sleep With Trazodone (REST)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: AMCI - Amnestic Mild Cognitive Impairment
Sleep Disturbance
Keywords: AMCI
Slow wave sleep
Trazodone
Cognition
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2022-03-16
Enrollment: 100
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: We will administer trazodone and placebo for 4 weeks each with a 4-week washout.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in total sleep duration between the treatment arms
timeFrame: Baseline and End of study, up to 12 weeks
measure: Change in Slow Wave Sleep (SWS) duration between the treatment arms
timeFrame: Baseline and End of study, up to 12 weeks
measure: Change in SWS intensity between the treatment arms
timeFrame: Baseline and End of study, up to 12 weeks
measure: Change in sleep onset latency between the treatment arms
timeFrame: Baseline and End of study, up to 12 weeks
measure: Change in sleep fragmentation between the treatment arms
timeFrame: Baseline and End of study, up to 12 weeks
measure: Change in self reported sleep measure Pittsburgh Sleep Quality Index (PSQI) between treatment arms
timeFrame: Baseline and End of study, up to 12 weeks
measure: Change in self reported sleep measure Epworth Sleepiness Score (ESS) between treatment arms
timeFrame: Baseline and End of study, up to 12 weeks
Secondary outcomes:
measure: Change in memory performance between treatment arms
timeFrame: Baseline and End of study, up to 12 weeks
measure: Change in hippocampal activation on Function Magnetic Resonance Imaging (fMRI) measures during memory functioning between treatment arms
timeFrame: Baseline and End of study, up to 12 weeks
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Barry Greenberg, PhD
role: PRINCIPAL_INVESTIGATOR
References: