Examining the link between depression and Alzheimer's disease

Depression Treatment and Aβ Dynamics: A Study of Alzheimer's Disease Risk (ABD Study)

This study tests if treating depression in older adults with an antidepressant can change markers related to Alzheimer's disease.

Quick facts

• Phase: PHASE4
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 60 Years and up
• Sex: All
• Sponsor: NYU Langone Health (other)
• Locations: 2 sites (New York, New York and 1 other locations)
• Trial ID: NCT05004987 on ClinicalTrials.gov

What this trial studies

This study investigates how treating major depressive disorder may influence the biological markers associated with Alzheimer's disease. It involves administering the SSRI antidepressant escitalopram to participants aged 60 and older who meet specific criteria for depression. The research aims to determine if alleviating depressive symptoms can lead to changes in Alzheimer's biomarkers in cerebrospinal fluid and inflammatory markers. By understanding this relationship, the study seeks to identify potentially modifiable risks for Alzheimer's disease.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 60 and older who have been diagnosed with major depressive disorder and are cognitively unimpaired.

Not a fit: Patients with significant neurological or systemic diseases that could interfere with the study may not benefit from participation.

Why it matters

Potential benefit: If successful, this study could provide insights into how managing depression may reduce the risk or delay the onset of Alzheimer's disease.

How similar studies have performed: While the relationship between depression and Alzheimer's disease has been explored, this specific approach of using an FDA-approved antidepressant to assess its impact on Alzheimer's biomarkers is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. Male and female subjects, age 60+ years inclusive, at the time of signing the informed consent.
2. Meeting Structured Clinical Interview (SCID-5-RV) for DSM-5 criteria for Major depressive disorder.
3. Montgomery-Åsberg Depression Rating Scale (MADRS) ≥18.
4. Have results of a physical examination, neurological examination, vitals, and EKG within normal limits at screening.
5. Cognitively unimpaired at screening visit as defined by Mini-Mental State Examination (MMSE) \>27.
6. Clinical Dementia Rating Scale (CDR) Global of 0\*.
7. A score of 85 or greater on the RBANS delayed memory index score.
8. 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.
9. Medically stable with no significant cerebrovascular, neurological, or systemic disease expected to interfere with the study.
10. Adequate auditory acuity and normal-to-corrected vision.
11. Willing to undergo brain MRI, urine drug screen and blood sampling for routine laboratory testing, lumbar puncture, APOE genotyping and plasma drug levels.
12. 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.

Exclusion Criteria:

1. 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.
2. Mental retardation, or other serious neurological disorder (e.g. Parkinson's disease or other movement disorders).
3. Subjects with a Fazekas scale \>2.
4. 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.).
5. A current significant risk for suicidality based on the Columbia-Suicide-Severity Rating Scale (C-SSRS).
6. Insulin dependent diabetes.
7. Evidence of clinically relevant or unstable cardiac, pulmonary, endocrine or hematological conditions.
8. Any prosthetic devices (e.g., pacemaker or surgical clips) that constitutes a hazard for MRI imaging.
9. Positive urine drug screen for illicit drugs.
10. History of poor tolerance to, poor response to, or ongoing treatment with escitalopram.
11. If taking antidepressants, currently taking fluoxetine, due to the length of time required to washout.
12. 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)

Where this trial is running

New York, New York and 1 other locations

• NYU Langone Health — New York, New York, United States (RECRUITING)
• Nathan S. Kline Institute for Psychiatric Research — Orangeburg, New York, United States (RECRUITING)

Study contacts

• Principal investigator: Nunzio Pomara, MD — NYU Langone Health
• Study coordinator: Antero Sarreal, MD

Conditions: Alzheimer Disease, Major Depressive Disorder