Alzheimer DiseasePhase 4NCT05004987
Aβ Dynamics in LLMD
A Phase 4 study testing Escitalopram Oxalate in people with Alzheimer Disease and Major Depressive Disorder, run by NYU Langone Health at 2 sites in United States.
Trial summary
This study will examine the biological factors that may modulate the relationship between depression and the development of Alzheimer's disease (AD). Since the direction of causation between depression and the biological factors associated with AD is unknown, the only way to understand cause and associated risk is to… Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Alzheimer Disease, Major Depressive Disorder
- What is being tested?
- Escitalopram Oxalate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 2 sitesUnited States
- Study dates
- 4 Feb 2022to 30 Jun 2027
- Phase
- Phase 4
- 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 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female subjects, age 60+ years inclusive, at the time of signing the informed consent.
- Meeting Structured Clinical Interview (SCID-5-RV) for DSM-5 criteria for Major depressive disorder.
- Montgomery-Åsberg Depression Rating Scale (MADRS) ≥18.
- Have results of a physical examination, neurological examination, vitals, and EKG within normal limits at screening.
- Cognitively unimpaired at screening visit as defined by Mini-Mental State Examination (MMSE) >27.
- Clinical Dementia Rating Scale (CDR) Global of 0*.
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- A score of 85 or greater on the RBANS delayed memory index score.
- Fluent in English, because some of the instruments used in this study have not been translated and validated in other languages, and are able to read at a 6th grade level or equivalent, as determined by the PI.
- Medically stable with no significant cerebrovascular, neurological, or systemic disease expected to interfere with the study.
- Adequate auditory acuity and normal-to-corrected vision.
- Willing to undergo brain MRI, urine drug screen and blood sampling for routine laboratory testing, lumbar puncture, APOE genotyping and plasma drug levels.
- Only individuals with normal or non-clinically significant abnormalities on routine laboratory tests, will be included.
- If study partner is not available, the CDR will be skipped.
Who cannot join
- History of brain tumor, MRI evidence of brain damage or brain disease including significant trauma, hydrocephalus, seizures, or confluent (or more extensive) white matter hyperintensities.
- Mental retardation, or other serious neurological disorder (e.g. Parkinson's disease or other movement disorders).
- Subjects with a Fazekas scale >2.
- Significant history of alcoholism or drug abuse in the past 2 years. Fulfilling SCID-5-RV/DSM-5 criteria for current or past diagnosis of any psychiatric disorder (e.g., schizophrenia, bipolar disorder, or any psychotic disorder) other than recurrent MDD or anxiety disorders (e.g., panic disorder, agoraphobia, etc.).
- A current significant risk for suicidality based on the Columbia-Suicide-Severity Rating Scale (C-SSRS).
- Insulin dependent diabetes.
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- Evidence of clinically relevant or unstable cardiac, pulmonary, endocrine or hematological conditions.
- Any prosthetic devices (e.g., pacemaker or surgical clips) that constitutes a hazard for MRI imaging.
- Positive urine drug screen for illicit drugs.
- History of poor tolerance to, poor response to, or ongoing treatment with escitalopram.
- If taking antidepressants, currently taking fluoxetine, due to the length of time required to washout.
- Treatment with following medications will not be permitted. In some cases, medications will be allowed if medically prescribed and dose regimen stable. Note: Some medications (e.g., amphetamines, opiates) may appear on the routine urine drug test in the screening period but can be allowed as per protocol.
- For subjects taking prescribed psychoactive medications and supplements (i.e., opioids, amphetamines, amphetamine-like substances, and cannabinoids), must be on a stable dose for 1 month prior to randomization.
- Anti-Parkinsonian medications (carbidopa/levodopa, amantadine, bromocriptine, pergolide, selegiline).
- Cholinesterase inhibitors and memantine
- Continuous aspirin (any dosage) use which can affect platelet function is prohibited. Exception: If participant is on low dose aspirin for prophylaxis and is willing to temporarily discontinue prior to research blood draw (i.e., 2 days before).
- Continuous use of other medications which are also known to affect platelet function, including nonsteroidal anti-inflammatory drugs (NSAIDs), anti-histamines. Exception: If participant is taking medication continuously and is willing to temporarily discontinue prior to research blood draw (i.e., 2 days before)
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
NYU Langone Health
New York, New York, 10016
Nunzio Pomara, MD
- Recruiting
Nathan S. Kline Institute for Psychiatric Research
Orangeburg, New York, 10962
Antero Sarreal, MD, 845-398-6532, Antero.sarreal@nki.rfmh.org
Nunzio Pomara, MD
About this study
Official title: Depression Treatment and Aβ Dynamics: A Study of Alzheimer's Disease Risk (ABD Study)
This study will examine the biological factors that may modulate the relationship between depression and the development of Alzheimer's disease (AD). Since the direction of causation between depression and the biological factors associated with AD is unknown, the only way to understand cause and associated risk is to treat the depressive symptoms and examine the effects on AD biomarkers. The study involves an FDA-approved treatment for major depressive disorder. It will compare the SSRI antidepressant escitalopram with placebo. The hypothesis is that a reduction in depressive symptoms will be associated with a normalization of CSF AD biomarkers as well as peripheral inflammatory markers. This research would contribute to fundamental knowledge about potentially modifiable risks of Alzheimer's disease (AD).
- Conditions
- Alzheimer Disease, Major Depressive Disorder
- Being tested
- Escitalopram Oxalate, Placebo
- Medical subject headings
- Alzheimer Disease, Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Escitalopram OxalateDrug
Also called Lexapro, ESC
The daily dose of ESC/PBO will be 10 mg for the first 2 weeks, then increase to 20 mg as tolerated, with an option to reduce back to 10 mg if necessary.
PlaceboDrug
Also called PBO
Daily dose of placebo will mimic that of ESC.
| Study group | Role | What they receive |
|---|---|---|
| Escitalopram (ESC) | Active comparator | Not described Receives: Drug: Escitalopram Oxalate |
| Placebo (PBO) | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Cerebrospinal Fluid (CSF) Aβ40 Biomarker Levels
Measured: Baseline, Week 8
Change in Cerebrospinal Fluid (CSF) Aβ42 Biomarker Levels
Measured: Baseline, Week 8
Change in Vascular Dysfunction (VD) Biomarker Levels
Measured: Baseline, Week 8
Change in Scores on Montgomery-Asberg Depression Ration Scale (MADRS)
MADRS consists of 10 items evaluating core symptoms of depression (e.g, apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thought, and suicidal thoughts). Each symptom is rated on a 0-6 scale (0=no abnormality, 6=severe). The total score ranges from 0 to 60; the higher the score, the more severe the symptoms.
Measured: Baseline, Week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2021
- Study start4 Feb 2022
- Primary completion31 Dec 2026 (estimated)
- Study completion30 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor
- Investigators
- Nunzio Pomara, MD, Principal investigator, NYU Langone Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05004987
- Sponsor's protocol ID
- 21-00535
- Status last verified
- May 2026
- First submitted
- 12 Aug 2021
- Last updated
- 6 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices) will be shared upon reasonable request.
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Depression Treatment and Aβ Dynamics: A Study of Alzheimer's Disease Risk (ABD Study)
- ClinicalTrials.gov ID
- NCT05004987
- Acronym / sponsor ID
- 21-00535
- Conditions
- Alzheimer Disease, Major Depressive Disorder
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 4 Feb 2022 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 30 Jun 2027 (estimated)
- First posted
- 13 Aug 2021 (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.
This study will examine the biological factors that may modulate the relationship between depression and the development of Alzheimer's disease (AD). Since the direction of causation between depression and the biological factors associated with AD is unknown, the only way to understand cause and associated risk is to treat the depressive symptoms and examine the effects on AD biomarkers. The study involves an FDA-approved treatment for major depressive disorder. It will compare the SSRI antidepressant escitalopram with placebo. The hypothesis is that a reduction in depressive symptoms will be associated with a normalization of CSF AD biomarkers as well as peripheral inflammatory markers. This research would contribute to fundamental knowledge about potentially modifiable risks of Alzheimer's disease (AD).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Escitalopram (ESC) | Active comparator | Drug: Escitalopram Oxalate |
| Placebo (PBO) | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Male and female subjects, age 60+ years inclusive, at the time of signing the informed consent.
- Meeting Structured Clinical Interview (SCID-5-RV) for DSM-5 criteria for Major depressive disorder.
- Montgomery-Åsberg Depression Rating Scale (MADRS) ≥18.
- Have results of a physical examination, neurological examination, vitals, and EKG within normal limits at screening.
- Cognitively unimpaired at screening visit as defined by Mini-Mental State Examination (MMSE) >27.
Key exclusion criteria (17 listed)
- History of brain tumor, MRI evidence of brain damage or brain disease including significant trauma, hydrocephalus, seizures, or confluent (or more extensive) white matter hyperintensities.
- Mental retardation, or other serious neurological disorder (e.g. Parkinson's disease or other movement disorders).
- Subjects with a Fazekas scale >2.
- Significant history of alcoholism or drug abuse in the past 2 years. Fulfilling SCID-5-RV/DSM-5 criteria for current or past diagnosis of any psychiatric disorder (e.g., schizophrenia, bipolar disorder, or any psychotic disorder) other than recurrent MDD or anxiety disorders (e.g., panic disorder, agoraphobia, etc.).
- A current significant risk for suicidality based on the Columbia-Suicide-Severity Rating Scale (C-SSRS).
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 |
|---|---|---|
| Escitalopram OxalateAlso: Lexapro, ESCThe daily dose of ESC/PBO will be 10 mg for the first 2 weeks, then increase to 20 mg as tolerated, with an option to reduce back to 10 mg if necessary. | Drug | Escitalopram (ESC) |
| PlaceboAlso: PBODaily dose of placebo will mimic that of ESC. | Drug | Placebo (PBO) |
Primary outcome
Change in Cerebrospinal Fluid (CSF) Aβ40 Biomarker Levels
Time frame: Baseline, Week 8
Change in Cerebrospinal Fluid (CSF) Aβ42 Biomarker Levels
Time frame: Baseline, Week 8
Change in Vascular Dysfunction (VD) Biomarker Levels
Time frame: Baseline, Week 8
Change in Scores on Montgomery-Asberg Depression Ration Scale (MADRS)
Time frame: Baseline, Week 8
MADRS consists of 10 items evaluating core symptoms of depression (e.g, apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thought, and suicidal thoughts). Each symptom is rated on a 0-6 scale (0=no abnormality, 6=severe). The total score ranges from 0 to 60; the higher the score, the more severe the symptoms.
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 6 May 2026.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices) will be shared upon reasonable request.
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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.
Nunzio Pomara, MD principal investigator
NYU Langone Health
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Escitalopram Oxalate in people with Alzheimer Disease and Major Depressive Disorder, run by NYU Langone Health at 2 sites 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 13 inclusion and 17 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 6 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 Antero Sarreal, MD (845-398-6532, Antero.sarreal@nki.rfmh.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Cerebrospinal Fluid (CSF) Aβ40 Biomarker Levels (time frame: Baseline, Week 8). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 May 2026.