Trazodone for Early Alzheimer's Disease

(REST Trial)

Overseen By Paul Rosenberg, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Johns Hopkins University

Must not be taking: Sleep medications

Disqualifiers: Under 55, Sleep apnea, Dementia, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether trazodone, a medication often used for sleep issues, can improve sleep and memory in individuals with early signs of Alzheimer's disease. Researchers aim to determine if it increases total sleep time and the amount of deep sleep (Slow Wave Sleep) a person gets. Participants will receive either trazodone or a placebo at different times during the study. Suitable candidates have mild memory problems and trouble sleeping but are generally healthy and can undergo an MRI scan. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop taking sleep medications, including trazodone, before participating.

Is there any evidence suggesting that trazodone is likely to be safe for humans?

Research has shown that trazodone is generally safe and often used, particularly by older adults. Many studies have found that trazodone can significantly improve sleep by increasing total sleep time and enhancing deep, restorative sleep, making it a promising option for those with sleep issues.

Although trazodone is commonly used, all medications can have side effects. However, many people tolerate trazodone well. For those considering joining a clinical trial involving trazodone, research supports its safety in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Alzheimer's?

Researchers are excited about trazodone for early Alzheimer's disease because it offers a potential new approach to managing this condition. Unlike most current treatments that focus on modifying neurotransmitter activity, trazodone is primarily known as an antidepressant but has shown promise in protecting brain cells and enhancing sleep quality, which can be beneficial for Alzheimer's patients. This dual action—neuroprotection and sleep improvement—sets trazodone apart, potentially addressing some symptoms and underlying disease mechanisms simultaneously.

What evidence suggests that trazodone might be an effective treatment for early Alzheimer's disease?

Research has shown that trazodone, which participants in this trial may receive, might help individuals with early Alzheimer's disease, particularly by improving sleep. In a study with 30 Alzheimer's patients, those who took trazodone slept about 42.5 minutes longer on average. This is significant because more deep sleep could enhance memory and brain function. Although older adults already use trazodone safely for other health issues, further research is needed to confirm its effects on memory and sleep in people with Alzheimer's. ^{2 3 6 7 8}

Who Is on the Research Team?

Barry Greenberg, PhD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

This trial is for adults with mild cognitive impairment, memory problems, and sleep complaints. They must be in good health, able to undergo MRI scans, and have a caregiver who can provide information. Excluded are those under 55, with severe sleep apnea or dementia, allergic to trazodone, using sleep meds or substances, having major psychiatric episodes or unstable medical conditions.

Inclusion Criteria

Are you older than 55?

Are you willing to wear a sleep monitor for four nights during the study? And are you willing to wear an actiwatch (like a fitbit) during the study?

Are you willing and able to undergo MRI brain imaging?

Exclusion Criteria

Are you currently taking Trazadone?

Are you currently taking any sleep medications that you're not willing or able to stop for two weeks prior to the study?

Do you need to use a CPAP?

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive trazodone or placebo for 4 weeks each, with a 4-week washout period in between

12 weeks

Multiple visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Trazodone

Trial Overview The study tests if Trazodone improves sleep and memory in early Alzheimer's by increasing total sleep time and Slow Wave Sleep (SWS). Participants will either receive Trazodone or a placebo without knowing which one they're taking.

How Is the Trial Designed?

Group I: Trazodone First Active Control 2 Interventions

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

Group II: Placebo First Placebo Group 2 Interventions

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

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

In a randomized controlled trial involving 30 patients with Alzheimer's disease, trazodone significantly improved sleep duration by an average of 42.5 minutes per night compared to placebo, indicating its efficacy in treating sleep disturbances.

Trazodone did not cause significant daytime sleepiness or cognitive impairment, suggesting it is a safe option for managing sleep issues in Alzheimer's patients without negatively affecting their cognitive function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trazodone improves sleep parameters in Alzheimer disease patients: a randomized, double-blind, and placebo-controlled study. Camargos, EF., Louzada, LL., Quintas, JL., et al.[2022]

In a study of 396 patients with Alzheimer's disease, trazodone was prescribed to 6.1% of patients, primarily for symptoms like irritability and agitation, and it effectively reduced irritability without increasing behavioral symptoms or caregiver burden over 6 months.

Patients treated with trazodone showed no worsening in overall behavioral and psychological symptoms of dementia (BPSD) or caregiver burden, indicating its safety and potential efficacy in managing specific symptoms in Alzheimer's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trazodone for Alzheimer's disease: a naturalistic follow-up study. López-Pousa, S., Garre-Olmo, J., Vilalta-Franch, J., et al.[2022]

In a study of 178 elderly patients with dementia, 38.2% experienced sleep disorders, with trazodone being the most commonly prescribed treatment, used by 35 patients.

Trazodone demonstrated an effectiveness rate of 65.7% in improving sleep disorders among these patients, indicating it is a viable treatment option for elderly individuals with dementia-related sleep issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trazodone for the treatment of sleep disorders in dementia: an open-label, observational and review study. Camargos, EF., Pandolfi, MB., Freitas, MP., et al.[2019]

In a study of 9,463 older adults with dementia, trazodone was found to have similar rates of falls and major osteoporotic fractures compared to atypical antipsychotics, indicating it is not necessarily a safer option for this population.

However, trazodone was associated with a lower rate of all-cause mortality, suggesting it may have some advantages in terms of overall survival compared to atypical antipsychotics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative risk of harm associated with trazodone or atypical antipsychotic use in older adults with dementia: a retrospective cohort study. Watt, JA., Gomes, T., Bronskill, SE., et al.[2022]

In a study of 25 participants with Alzheimer's disease or mild cognitive impairment, those taking trazodone for sleep experienced a significantly slower cognitive decline compared to non-users, with a decline rate 2.4 times greater in non-users over four years.

Trazodone not only improves sleep quality, particularly enhancing deep slow-wave sleep, but also has a unique mechanism of action affecting serotonin and adrenergic receptors, suggesting it may have potential benefits for cognitive health in the elderly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Alzheimer's Disease: Trazodone, Sleep, Serotonin, Norepinephrine, and Future Directions. Ashford, JW.[2020]

In a review of two studies involving 104 participants with dementia, trazodone did not show statistically significant benefits over placebo for managing behavioral and psychological symptoms associated with dementia.

Despite its sedative and antidepressant properties, the evidence is insufficient to recommend trazodone for dementia-related behavioral disturbances, highlighting the need for longer and larger trials to better assess its efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trazodone for agitation in dementia. Martinon-Torres, G., Fioravanti, M., Grimley, EJ.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12279255/

A Randomized-Controlled Trial Targeting Cognition in Early ... Trazodone, a safe and widely used drug in the older adult population, has shown promise in inducing slow wave sleep in older adults, but requires more rigorous ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05282550

NCT05282550 | Targeting Cognition in Early Alzheimer's ... The investigators hypothesize that trazodone will improve total sleep time and proportion of time in Slow Wave Sleep (SWS). Detailed Description. The REST trial ...

3. alzdiscovery.org alzdiscovery.org/uploads/cognitive_vitality_media/Trazodone-Cognitive-Vitality-For-Researchers.pdf

Trazodone Trazodone effects on MMSE remained significant within participants with probable Alzheimer's disease, with a 2.4-fold faster decline in non ...

4. withpower.com withpower.com/trial/phase-2-alzheimer-disease-5-2022-7d57e

Trazodone for Early Alzheimer's Disease (REST Trial) In a randomized controlled trial involving 30 patients with Alzheimer's disease, trazodone significantly improved sleep duration by an average of 42.5 minutes ...

5. alzheimers.gov alzheimers.gov/clinical-trials/trazodone-improve-sleep-and-memory-people-early-alzheimers-disease

Trazodone To Improve Sleep and Memory in People With ... This Phase 2 study, named REST, will examine the effectiveness of the FDA-approved drug trazodone to improve sleep and memory in people with mild cognitive ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39422935/

A Randomized-Controlled Trial Targeting Cognition in Early ... Trazodone, a safe and widely used drug in the older adult population, has shown promise in inducing slow wave sleep in older adults, but requires more rigorous ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6363148/

Trazodone use and risk of dementia: A population-based ... Crude results showed that trazodone users were more likely to be diagnosed with dementia earlier (median = 1.7 years; IQR = 0.4–4.7 years) ...

8. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/gps.5625

Effect of trazodone on cognitive decline in people ... There was no evidence of cognitive benefit from trazodone compared to other antidepressants in people with dementia in three naturalistic cohort studies.