Memantine Augmentation of Targeted Cognitive Training in Schizophrenia

NCT04857983 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 201502
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

Treatment of schizophrenia currently includes antipsychotic medications and cognitive therapies which improve some symptoms, but do not sufficiently restore cognitive functioning or reduce psychosocial disability. We hypothesize that medications that specifically target sensory information processing deficits, rather than psychotic symptoms per se, will significantly enhance the benefits of a sensory-based targeted cognitive training (TCT) intervention in patients with schizophrenia. We will complete a randomized, double-blind clinical trial to: 1) confirm that the drug memantine augments TCT learning; 2) determine whether memantine enhances the clinical benefits from a full 30 session course of TCT vs. TCT plus placebo in antipsychotic- medicated schizophrenia patients, and 3) determine if memantine's enhancement of TCT is most effective in biomarker-defined subgroups of patients.

Conditions

Schizophrenia; Schizoaffective Disorder

Keywords

schizophrenia; cognitive training; EEG

Outcome Measures

Primary Outcomes (3)

• Positive & Negative Symptom Scale Total (PANSSt)

  PANSS Total Score is the primary clinical outcome measured at baseline vs. post TCT session 10, 20 and 30 (approximately 16 weeks). The PANSS total score has a range 30-210, with higher scores indicating worse outcome.

  Baseline (at study enrollment), post-10 TCT sessions (approximately week 10), post-20 TCT sessions (approximately week 13) and post-30 TCT sessions (approximately week 16).

• World Health Organization Disability Schedule (WHODAS 2.0)

  Function will be assessed via the World Health Organization Disability Schedule 2.0 (WHODAS 2.0) at baseline vs. post-TCT session 10, 20 and 30 (approximately 16 weeks). The World Health Organization Disability Schedule (WHODAS 2.0) has a range 12-60, with higher scores indicating worse outcome.

  Baseline (at study enrollment), post-10 TCT sessions (approximately week 10), post-20 TCT sessions (approximately week 13) and post-30 TCT sessions (approximately week 16).

• MATRICS Consensus Cognitive Battery Global Composite T-score (MCCB-C)

  The MCCB Global Composite T-score (MCCB-C) is the primary neurocognitive outcome measured at baseline vs. post-TCT session 10, 20 and 30 (approximately 16 weeks). The MATRICS Consensus Cognitive Battery (MCCB) composite T-score has no minimum or maximum score because it uses T-scores (e.g., 50 indicates the population mean with a standard deviation of 10), which are standardized based on a community sample. A normal range MCCB composite T-score is between 40 and 60 and higher scores indicate better neurocognitive outcome.

  Baseline (at study enrollment), post-10 TCT sessions (approximately week 10), post-20 TCT sessions (approximately week 13) and post-30 TCT sessions (approximately week 16).

Secondary Outcomes (5)

• Positive & Negative Symptom Scale (PANSS) - Positive Symptom Subscale

  Baseline (at study enrollment), post-10 TCT sessions (approximately week 10), post-20 TCT sessions (approximately week 13) and post-30 TCT sessions (approximately week 16).

• Positive & Negative Symptom Scale (PANSS) - Negative Symptom Subscale

  Baseline (at study enrollment), post-10 TCT sessions (approximately week 10), post-20 TCT sessions (approximately week 13) and post-30 TCT sessions (approximately week 16).

• Psychotic Symptoms - PSYRATS Hallucination Subscale

  Baseline (at study enrollment), post-10 TCT sessions (approximately week 10), post-20 TCT sessions (approximately week 13) and post-30 TCT sessions (approximately week 16).

• Manic Symptoms - Young Mania Rating Scale

  Baseline (at study enrollment), post-10 TCT sessions (approximately week 10), post-20 TCT sessions (approximately week 13) and post-30 TCT sessions (approximately week 16).

• Current Depressive Symptoms - PHQ-9

  Baseline (at study enrollment), post-10 TCT sessions (approximately week 10), post-20 TCT sessions (approximately week 13) and post-30 TCT sessions (approximately week 16).

Study Arms (2)

TCT + PBO

PLACEBO COMPARATOR

Subjects will be assigned to take placebo and will complete 30 hours of targeted cognitive training in order to assess whether memantine enhances cognitive training performance

Drug: Placebo

TCT + MEM

ACTIVE COMPARATOR

Subjects will be assigned to take memantine and will complete 30 hours of targeted cognitive training in order to assess whether memantine enhances cognitive training performance

Drug: Memantine

Interventions

Memantine DRUG

Subjects will be assigned to take memantine or placebo and will complete 30 hours of targeted cognitive training in order to assess whether memantine enhances cognitive training performance

Also known as: targeted cognitive training (TCT)

TCT + MEM

Placebo DRUG

Subjects will be assigned to take memantine or placebo and will complete 30 hours of targeted cognitive training in order to assess whether memantine enhances cognitive training performance

Also known as: targeted cognitive training (TCT)

TCT + PBO

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• DSM-IV diagnosis of schizophrenia or schizoaffective disorder
• Written informed consent to participate in the study
• Age 18-65
• Absence of dementia or mental retardation
• Urine toxicology negative for recreational drugs
• Fluent and literate in English

You may not qualify if:

• Meets DSM-IV criteria for current substance abuse or dependence and has been substance abstinent for less than 30 days
• A history of traumatic brain injury
• Auditory or visual impairments severe enough to prevent study participation
• Under conservatorship (determined by Anasazi)
• Pregnancy

Sponsors & Collaborators

• University of California, San Diego: lead

Study Sites (1)

Clinical Teaching Facility (CTF B-403 at UCSD Medical Center)

San Diego, California, 92103, United States

Location

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Interventions

Memantine

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Amantadine; Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Gregory A. Light, Ph.D.
• Organization: University of California San Diego, Department of Psychiatry

glight@health.ucsd.edu

619-316-6242

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Subjects will be randomized to TCT and memantine or TCT and placebo. The research will be provided with a randomization scheme to follow and will dispense the pills identified only by a code.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Subjects will be randomized to targeted cognitive training (TCT) and memantine (MEM) or targeted cognitive training (TCT) and placebo (PBO)

Study Record Dates

• First Submitted: April 21, 2021
• First Posted: April 23, 2021
• Study Start: July 6, 2021
• Primary Completion: March 30, 2025
• Study Completion: March 30, 2025
• Last Updated: May 18, 2026
• Results First Posted: May 18, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)