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

Sleep Disturbance Clinical Trial

— REST  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05282550
• Other study ID #: IRB00301426
• Secondary ID: R01AG071522
• Status: Recruiting
• Phase: Phase 2
• Start date: January 4, 2023
• Est. completion date: May 2028

Study information

• Verified date: January 2024
• Source: Johns Hopkins University
• Contact: Barry Greenberg, PhD
• Phone: 410-955-1696
• Email: bgreen45[@]jhmi.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: May 2028
• Est. primary completion date: March 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Cognitive Dysfunction
• Dyssomnias
• Parasomnias
• Sleep Disturbance

Intervention

Drug:
• Trazodone
50mg of trazodone administered for 4 weeks.
• Placebo
Placebo administered for 4 weeks.

Locations

Country	Name	City	State
United States	Johns Hopkins Hospital	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Johns Hopkins University	National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in total sleep duration between the treatment arms	Comparison of means of total sleep duration from baseline measured in minutes between trazodone and placebo arm.	Baseline and End of study, up to 12 weeks
Primary	Change in Slow Wave Sleep (SWS) duration between the treatment arms	Comparison of means of SWS from baseline measured in minutes between trazodone and placebo arm.	Baseline and End of study, up to 12 weeks
Primary	Change in SWS intensity between the treatment arms	Comparison of means of SWS intensity measured from baseline in volts squared between trazodone and placebo arm.	Baseline and End of study, up to 12 weeks
Primary	Change in sleep onset latency between the treatment arms	Comparison of means of sleep onset latency from baseline measured in minutes between trazodone and placebo arm.	Baseline and End of study, up to 12 weeks
Primary	Change in sleep fragmentation between the treatment arms	Comparison of means of sleep fragmentation from baseline measured in minutes between trazodone and placebo arm.	Baseline and End of study, up to 12 weeks
Primary	Change in self reported sleep measure Pittsburgh Sleep Quality Index (PSQI) between treatment arms	Comparison of means score for PSQI from baseline between trazodone and placebo arm. A higher score means a worse outcome.	Baseline and End of study, up to 12 weeks
Primary	Change in self reported sleep measure Epworth Sleepiness Score (ESS) between treatment arms	Comparison of means score for ESS from baseline between trazodone and placebo arm. A higher score means a worse outcome.	Baseline and End of study, up to 12 weeks
Secondary	Change in memory performance between treatment arms	Comparison of means for memory performance from baseline measured in percent correct between trazodone and placebo arm.	Baseline and End of study, up to 12 weeks
Secondary	Change in hippocampal activation on Function Magnetic Resonance Imaging (fMRI) measures during memory functioning between treatment arms	Comparison of means of hippocampal activation on fMRI measures calculated as a beta weight reflecting relative activation during memory functioning from baseline between trazodone and placebo arm. Higher activation suggests a worse outcome.	Baseline and End of study, up to 12 weeks