AMCI - Amnestic Mild Cognitive ImpairmentPhase 2RESTNCT05282550
Targeting Cognition in Early Alzheimer's Disease by Improving Sleep With Trazodone
A Phase 2 study testing Trazodone in people with AMCI - Amnestic Mild Cognitive Impairment and Sleep Disturbance, run by Johns Hopkins University at 1 site in United States.
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). Read more about this study
- Who is it for?
- Ages 55 years and older
- Conditions the study is for
- AMCI - Amnestic Mild Cognitive Impairment, Sleep Disturbance
- What is being tested?
- Trazodone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Feb 2023to 30 Jun 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- Able to have Magnetic Resonance Imaging (MRI) scan;
- Availability of knowledgeable informant (KI)
- Buschke Selective Reminding Test or more standard deviations below age-education norms
Who cannot join
- 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;
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Johns Hopkins Hospital
Baltimore, Maryland, 21205
Barry Greenberg, PhD, 410-955-1696, bgreen45@jhmi.edu
Paul Rosenberg, MD, 410-550-9883, prosenb9@jhmi.edu
About this study
Official title: RCT Targeting Cognition in Early Alzheimer's Disease by Improving Sleep With Trazodone (REST)
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).
Read the 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.
- Being tested
- Trazodone, Placebo
- Keywords
- AMCI, Slow wave sleep, Trazodone, Cognition
- Medical subject headings
- Parasomnias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TrazodoneDrug
Also called Desyrel
50mg of trazodone administered for 4 weeks.
PlaceboDrug
Placebo administered for 4 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Trazodone First | Active comparator | Trazodone (50 mg at bedtime) and then placebo after a 4-week washout period. Receives: Drug: Trazodone; Drug: Placebo |
| Placebo First | Placebo comparator | Placebo and then Trazodone (50 mg at bedtime) after a 4-week washout period. Receives: Drug: Trazodone; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and End of study, up to 12 weeks
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.
Measured: Baseline and End of study, up to 12 weeks
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.
Measured: Baseline and End of study, up to 12 weeks
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.
Measured: Baseline and End of study, up to 12 weeks
Change in sleep fragmentation between the treatment arms
Comparison of means of sleep fragmentation from baseline measured in minutes between trazodone and placebo arm.
Measured: Baseline and End of study, up to 12 weeks
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.
Measured: Baseline and End of study, up to 12 weeks
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.
Measured: Baseline and End of study, up to 12 weeks
Secondary outcomes (2)
Change in memory performance between treatment arms
Comparison of means for memory performance from baseline measured in percent correct between trazodone and placebo arm.
Measured: Baseline and End of study, up to 12 weeks
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.
Measured: Baseline and End of study, up to 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2022
- Study start2 Feb 2023
- Primary completion30 Jul 2027 (estimated)
- Study completion30 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AMCI - Amnestic Mild Cognitive ImpairmentStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- We will administer trazodone and placebo for 4 weeks each with a 4-week washout.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor
- Investigators
- Barry Greenberg, PhD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05282550
- Sponsor's protocol ID
- IRB00301426
- Other IDs
- R01AG071522
- Acronym
- REST
- Status last verified
- Jun 2026
- First submitted
- 8 Mar 2022
- Last updated
- 17 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Eyob E, Shaw JS, Bakker A, Munro C, Spira A, Wu M, Rabinowitz JA, Peters M, Wanigatunga S, Zipunnikov V, Thompson R, Burhanullah MH, Leoutsakos JM, Rosenberg P, Greenberg B. A Randomized-Controlled Trial Targeting Cognition in Early Alzheimer's Disease by Improving Sleep with Trazodone (REST). J Alzheimers Dis. 2024;101(s1):S205-S215. doi: 10.3233/JAD-230635.
PubMed 39422935
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- RCT Targeting Cognition in Early Alzheimer's Disease by Improving Sleep With Trazodone (REST)
- ClinicalTrials.gov ID
- NCT05282550
- Acronym / sponsor ID
- REST / IRB00301426
- Keywords
- AMCI, Slow wave sleep, Trazodone, Cognition
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 2 Feb 2023 (actual)
- Primary completion
- 30 Jul 2027 (estimated)
- Study completion
- 30 Jun 2028 (estimated)
- First posted
- 16 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- We will administer trazodone and placebo for 4 weeks each with a 4-week washout.
| Arm | Type | Receives |
|---|---|---|
| Trazodone First | Active comparator | Drug: Trazodone, Drug: PlaceboTrazodone (50 mg at bedtime) and then placebo after a 4-week washout period. |
| Placebo First | Placebo comparator | Drug: Trazodone, Drug: PlaceboPlacebo and then Trazodone (50 mg at bedtime) after a 4-week washout period. |
Who may qualify
- Ages
- 55 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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;
Key exclusion criteria (14 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TrazodoneAlso: Desyrel50mg of trazodone administered for 4 weeks. | Drug | Placebo First, Trazodone First |
| PlaceboPlacebo administered for 4 weeks. | Drug | Placebo First, Trazodone First |
Primary outcome
Change in total sleep duration between the treatment arms
Time frame: Baseline and End of study, up to 12 weeks
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
Time frame: Baseline and End of study, up to 12 weeks
Comparison of means of SWS from baseline measured in minutes between trazodone and placebo arm.
Change in SWS intensity between the treatment arms
Time frame: Baseline and End of study, up to 12 weeks
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
Time frame: Baseline and End of study, up to 12 weeks
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
Time frame: Baseline and End of study, up to 12 weeks
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
Time frame: Baseline and End of study, up to 12 weeks
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
Time frame: Baseline and End of study, up to 12 weeks
Comparison of means score for ESS from baseline between trazodone and placebo arm. A higher score means a worse outcome.
2 secondary outcomes
Change in memory performance between treatment arms
Time frame: Baseline and End of study, up to 12 weeks
Change in hippocampal activation on Function Magnetic Resonance Imaging (fMRI) measures during memory functioning between treatment arms
Time frame: Baseline and End of study, up to 12 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jun 2026.
- Derived from this study: PubMed 39422935Eyob E, Shaw JS, Bakker A, Munro C, Spira A, Wu M, Rabinowitz JA, Peters M, Wanigatunga S, Zipunnikov V, Thompson R, Burhanullah MH, Leoutsakos JM, Rosenberg P, Greenberg B. A Randomized-Controlled Trial Targeting Cognition in Early Alzheimer's Disease by Improving Sleep with Trazodone (REST). J Alzheimers Dis. 2024;101(s1):S205-S215. doi: 10.3233/JAD-230635.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Barry Greenberg, PhD principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Trazodone in people with AMCI - Amnestic Mild Cognitive Impairment and Sleep Disturbance, run by Johns Hopkins University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Barry Greenberg, PhD (410-955-1696, bgreen45@jhmi.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in total sleep duration between the treatment arms (time frame: Baseline and End of study, up to 12 weeks). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05282550, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jun 2026.