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

Primary Purpose

AMCI - Amnestic Mild Cognitive Impairment, Sleep Disturbance

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Trazodone

Placebo

About this trial

This is an interventional treatment trial for AMCI - Amnestic Mild Cognitive Impairment focused on measuring AMCI, Slow wave sleep, Trazodone, Cognition

Eligibility Criteria

55 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Mild Cognitive Impairment (MCI) as defined by Albert et al.2 including subjective memory complaint and/or objective evidence of memory problems;
Clinical Dementia Rating (CDR) of 0.5 with a Memory Box score of >=0.5;
Evidence of sleep complaints with Pittsburgh Sleep Quality Index score of >5 (a well-validated cutoff observed in >40% of older persons);
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;
Visual and auditory acuity adequate for neuropsychological testing;
Good general health with no disease expected to interfere with the study;
Able to have Magnetic Resonance Imaging (MRI) scan;
Availability of knowledgeable informant (KI)

Exclusion Criteria:

Less than 55 years of age to reduce likelihood of including individuals with frontotemporal dementia or non-dementia MCI;
Too frail or medically unstable to undergo study procedures;
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;
Dementia;
Cognitive complaints and deficits better explained by other medical/neurologic conditions;
Delirium;
Allergic to trazodone;
Taking sleep medications including trazodone;
Current substance abuse;
Current major depressive, manic, or acute psychotic episode;
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:
Lack of available KI;
Prior diagnosis of Q wave T wave Corrected for heart rate (QTc) > 470 msec (females) or > 450 msec (males);
Inability to provide informed consent

Sites / Locations

Johns Hopkins HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Trazodone First

Placebo First

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

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.

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.

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.

Change in sleep fragmentation between the treatment arms

Comparison of means of sleep fragmentation from baseline measured in minutes between trazodone and placebo arm.

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.

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.

Secondary Outcome Measures

Change in memory performance between treatment arms

Comparison of means for memory performance from baseline measured in percent correct between trazodone and placebo arm.

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.

Full Information

NCT ID

NCT05282550

First Posted

March 8, 2022

Last Updated

January 5, 2023

Sponsor

Johns Hopkins University

Collaborators

National Institute on Aging (NIA)

1. Study Identification

Unique Protocol Identification Number

NCT05282550

Brief Title

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

Acronym

REST

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Recruiting

Study Start Date

January 4, 2023 (Actual)

Primary Completion Date

March 2027 (Anticipated)

Study Completion Date

May 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Johns Hopkins University

Collaborators

National Institute on Aging (NIA)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

AMCI - Amnestic Mild Cognitive Impairment, Sleep Disturbance

Keywords

AMCI, Slow wave sleep, Trazodone, Cognition

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Crossover Assignment

Model Description

We will administer trazodone and placebo for 4 weeks each with a 4-week washout.

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

Study drug will be compounded by the Investigational Drug Service (IDS) at Johns Hopkins Bayview Medical Center. The IDS will prepare blind medication using opaque capsules and randomly assign eligible participants to treatment order (ie, starting with trazodone vs. placebo treatment).

Allocation

Randomized

Enrollment

100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Trazodone First

Arm Type

Active Comparator

Arm Description

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

Arm Title

Placebo First

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Trazodone

Other Intervention Name(s)

Desyrel

Intervention Description

50mg of trazodone administered for 4 weeks.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo administered for 4 weeks.

Primary Outcome Measure Information:

Title

Change in total sleep duration between the treatment arms

Description

Comparison of means of total sleep duration from baseline measured in minutes between trazodone and placebo arm.

Time Frame

Baseline and End of study, up to 12 weeks

Title

Change in Slow Wave Sleep (SWS) duration between the treatment arms

Description

Comparison of means of SWS from baseline measured in minutes between trazodone and placebo arm.

Time Frame

Baseline and End of study, up to 12 weeks

Title

Change in SWS intensity between the treatment arms

Description

Comparison of means of SWS intensity measured from baseline in volts squared between trazodone and placebo arm.

Time Frame

Baseline and End of study, up to 12 weeks

Title

Change in sleep onset latency between the treatment arms

Description

Comparison of means of sleep onset latency from baseline measured in minutes between trazodone and placebo arm.

Time Frame

Baseline and End of study, up to 12 weeks

Title

Change in sleep fragmentation between the treatment arms

Description

Comparison of means of sleep fragmentation from baseline measured in minutes between trazodone and placebo arm.

Time Frame

Baseline and End of study, up to 12 weeks

Title

Change in self reported sleep measure Pittsburgh Sleep Quality Index (PSQI) between treatment arms

Description

Comparison of means score for PSQI from baseline between trazodone and placebo arm. A higher score means a worse outcome.

Time Frame

Baseline and End of study, up to 12 weeks

Title

Change in self reported sleep measure Epworth Sleepiness Score (ESS) between treatment arms

Description

Comparison of means score for ESS from baseline between trazodone and placebo arm. A higher score means a worse outcome.

Time Frame

Baseline and End of study, up to 12 weeks

Secondary Outcome Measure Information:

Title

Change in memory performance between treatment arms

Description

Comparison of means for memory performance from baseline measured in percent correct between trazodone and placebo arm.

Time Frame

Baseline and End of study, up to 12 weeks

Title

Change in hippocampal activation on Function Magnetic Resonance Imaging (fMRI) measures during memory functioning between treatment arms

Description

Time Frame

Baseline and End of study, up to 12 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Mild Cognitive Impairment (MCI) as defined by Albert et al.2 including subjective memory complaint and/or objective evidence of memory problems; Clinical Dementia Rating (CDR) of 0.5 with a Memory Box score of >=0.5; Evidence of sleep complaints with Pittsburgh Sleep Quality Index score of >5 (a well-validated cutoff observed in >40% of older persons); 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; Visual and auditory acuity adequate for neuropsychological testing; Good general health with no disease expected to interfere with the study; Able to have Magnetic Resonance Imaging (MRI) scan; Availability of knowledgeable informant (KI) Exclusion Criteria: Less than 55 years of age to reduce likelihood of including individuals with frontotemporal dementia or non-dementia MCI; Too frail or medically unstable to undergo study procedures; 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; Dementia; Cognitive complaints and deficits better explained by other medical/neurologic conditions; Delirium; Allergic to trazodone; Taking sleep medications including trazodone; Current substance abuse; Current major depressive, manic, or acute psychotic episode; 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: Lack of available KI; Prior diagnosis of Q wave T wave Corrected for heart rate (QTc) > 470 msec (females) or > 450 msec (males); Inability to provide informed consent

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Barry Greenberg, PhD

Phone

410-955-1696

bgreen45@jhmi.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Paul Rosenberg, MD

Phone

410-550-9883

prosenb9@jhmi.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Barry Greenberg, PhD

Organizational Affiliation

Johns Hopkins University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Johns Hopkins Hospital

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21205

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Barry Greenberg, PhD

Phone

410-955-1696

bgreen45@jhmi.edu

First Name & Middle Initial & Last Name & Degree

Paul Rosenberg, MD

Phone

410-550-9883

prosenb9@jhmi.edu

First Name & Middle Initial & Last Name & Degree

Barry Greenberg, PhD

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

The Executive Committee of the study, consisting of the study PIs and the Director of the Data Coordinating Center for this study will oversee the deidentified Individual Participant Data (IPD) sharing. This will include the review of requests for trial data and samples. The Executive Committee will assure that all investigators who receive data and/or specimens are qualified investigators, with research goals consistent with those stated in the consent form. A Material Transfer Agreement (MTA) and/or Data Use Agreement (DUA) will be in place with approved requestors before any transfer of bio-samples or data. Investigators receiving the data and/or samples will be required to cite the grant in any publications generated by the data and to send a copy of all publications to the study team.

IPD Sharing Time Frame

1 year after study completion

IPD Sharing Access Criteria

Upon approval of data analytic strategy by study team

Learn more about this trial

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

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