Pattern Separation in Major Depressive Disorder

NCT07139834 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 00081503
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study seeks to examine the effects of treatment with a selective serotonin reuptake inhibitor (SSRI), escitalopram, a first-line treatment for depression, in combination with placebo or with extended-release memantine, on neuropsychological function, regional brain activity assessed by functional magnetic resonance imaging, and depressive symptoms, in participants with Major Depressive Disorder. Escitalopram is administered in an open-label fashion in this study; extended release memantine is administered in a double-blind, randomized, placebo-controlled manner.

Conditions

Major Depressive Disorder (MDD)

Keywords

Depression; Major depressive disorder; MDD; Pattern separation; Memantine

Outcome Measures

Primary Outcomes (1)

• Pattern Separation Performance

  Participants will complete a pattern separation task

  At baseline (week 0) and after completing the medication trial (week 11)

Secondary Outcomes (1)

• Depression Severity

  At screening, baseline (week 0) and after completing the medication trial (week 11)

Study Arms (2)

SSRI + Memantine

EXPERIMENTAL

Drug: SSRI (escitalopram or sertraline); Drug: Extended-Release Memantine

SSRI + Placebo

PLACEBO COMPARATOR

Drug: SSRI (escitalopram or sertraline); Drug: Placebo

Interventions

SSRI (escitalopram or sertraline) DRUG

11 weeks of open-label treatment with an SSRI, of which the last 6 weeks are augmented with memantine vs placebo. Primary SSRI for the study is escitalopram. In cases of prior intolerance or non-response to escitalopram, individuals will be treated with sertraline instead of escitalopram.

SSRI + Memantine; SSRI + Placebo

Extended-Release Memantine DRUG

6 weeks of treatment with extended-release memantine as augmentation to ongoing escitalopram treatment

SSRI + Memantine

Placebo DRUG

6 weeks of treatment with placebo as augmentation to ongoing escitalopram treatment

SSRI + Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-50
• Current diagnosis of MDD without psychotic features assessed within three weeks of study enrollment
• item Hamilton Depression Rating Scale score ≥17 assessed within 3 weeks of study enrollment
• Using an effective form of contraception at study enrollment and agrees to continue throughout study participation for individuals of child-bearing potential
• Capacity to provide informed consent
• Proficient in English
• Willing to provide emergency contact

You may not qualify if:

• Currently taking an antidepressant medication at study enrollment
• Pregnant or breastfeeding at time of enrollment
• Evidence of current unstable medical illness, including liver or renal impairment, or unstable cardiovascular or respiratory illness
• QTc interval greater than 500 ms
• Current genitourinary conditions that raise urine pH such as a) renal tubular acidosis or b) severe infection of the urinary tract.
• Lifetime diagnosis of a) bipolar disorder, b) psychotic disorder, or c) dementia
• Current active suicidal ideation
• Current substance use disorder other than tobacco use disorder
• Current or recent (past 6 months) treatment with antipsychotics; current or recent (past 1 month) treatment with benzodiazepines; current use of prescribed stimulant medication; current use of other NMDA antagonists (amantadine, ketamine, dextromethorphan)
• Current use of disulfiram with oral concentrate, MAOIs (including linezolid or IV methylene blue), or pimozide
• History of hypersensitivity or allergic reaction to a) memantine hydrochloride or any of its components/excipients, b) citalopram, escitalopram, or any other component of the product, or c) sertraline or any other component of the product
• Concurrent or recent (past 6 months) participation in another clinical trial for mental illness involving an investigational product or device
• Lack of response to or intolerable side-effects from trials of two or more selective serotonin reuptake inhibitors of adequate dose and duration at study enrollment
• Electroconvulsive therapy (ECT) in the past 6 months
• Any condition or material in the body that is a contraindication for MRI procedures

Sponsors & Collaborators

• Jeffrey Miller: lead

Study Sites (1)

New York State Psychiatric Institute (NYSPI)

New York, New York, 10032, United States

Location

Related Publications (2)

• Beevers CG, Mullarkey MC, Dainer-Best J, Stewart RA, Labrada J, Allen JJB, McGeary JE, Shumake J. Association between negative cognitive bias and depression: A symptom-level approach. J Abnorm Psychol. 2019 Apr;128(3):212-227. doi: 10.1037/abn0000405. Epub 2019 Jan 17.

  PMID: 30652884 BACKGROUND

• Phillips TO, Castro M, Vas RK, Ferguson LA, Harikumar A, Leal SL. Perceived antidepressant efficacy associated with reduced negative and enhanced neutral mnemonic discrimination. Front Hum Neurosci. 2023 Aug 28;17:1225836. doi: 10.3389/fnhum.2023.1225836. eCollection 2023.

  PMID: 37701502 BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Interventions

Selective Serotonin Reuptake Inhibitors; Escitalopram; Sertraline

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Neurotransmitter Agents; Serotonin Agents; Physiological Effects of Drugs; Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; 1-Naphthylamine; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• Jeffrey M Miller, MD

  New York State Psychiatric Institute (NYSPI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jeffrey M Miller, MD

CONTACT

646-774-7613; jeffrey.miller@nyspi.columbia.edu

Gabriella F Restifo-Bernstein, BA

CONTACT

646-774-8138; gabriella.restifo@nyspi.columbia.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Study coordinator
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Research Scientist

Study Record Dates

• First Submitted: August 15, 2025
• First Posted: August 24, 2025
• Study Start: April 1, 2026
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2028
• Last Updated: March 3, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: IPD and supporting information will be made available within one year following the conclusion of study recruitment, with no specified end point.
• Access Criteria: Sharing of the IPD described above with investigators outside the study team will occur through institutionally approved mechanisms that may require a data use agreement. Requests for sharing of IPD can be made to the study's principal investigator, who will confirm that all institutional requirements are met prior to data sharing.

Locations

US (1)