Aβ Dynamics in LLMD

Major Depressive Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05004987
• Other study ID #: 21-00535
• Status: Recruiting
• Phase: Phase 4
• Start date: February 4, 2022
• Est. completion date: June 2026

Study information

• Verified date: October 2023
• Source: NYU Langone Health
• Contact: Antero Sarreal, MD
• Phone: 845-398-6532
• Email: Antero.sarreal[@]nki.rfmh.org
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: June 2026
• Est. primary completion date: April 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

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 hepatic and renal function including normal creatinine clearance will be included.

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)

Related Conditions & MeSH terms

• Alzheimer Disease
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Drug:
• Escitalopram Oxalate
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.
• Placebo
Daily dose of placebo will mimic that of ESC.

Locations

Country	Name	City	State
United States	NYU Langone Health	New York	New York
United States	Nathan S. Kline Institute for Psychiatric Research	Orangeburg	New York

Sponsors (2)

Lead Sponsor	Collaborator
NYU Langone Health	National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in Plasma Aß Biomarker Levels		Baseline, Week 8
Other	Change in Cerebrospinal Fluid (CSF) P-tau Biomarker Levels		Baseline, Week 8
Other	Change in Cerebrospinal Fluid (CSF) T-tau Biomarker Levels		Baseline, Week 8
Primary	Change in Cerebrospinal Fluid (CSF) Aß40 Biomarker Levels		Baseline, Week 8
Primary	Change in Cerebrospinal Fluid (CSF) Aß42 Biomarker Levels		Baseline, Week 8
Primary	Change in Vascular Dysfunction (VD) Biomarker Levels		Baseline, Week 8
Primary	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.	Baseline, Week 8