Memantine Augmentation of Targeted Cognitive Training in Schizophrenia

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.

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Schizoaffective Disorder
• Intervention / Treatment: Drug: Placebo; Drug: Memantine

Detailed Description

Treatment of schizophrenia (SZ) currently includes antipsychotic medications and cognitive therapies which improve some symptoms, but do not sufficiently restore cognitive functioning or reduce psychosocial disability. We propose and will test a novel "augmentation strategy" for using medications to specifically enhance the benefits of targeted cognitive training (TCT) in schizophrenia. This project tests a rational and empirically supported platform for augmenting the benefits of TCT in antipsychotic medicated SZ patients by adjunctive daily treatment of 20 mg memantine, an FDA approved medication for the treatment of cognitive dysfunction in Alzheimer's Disease. 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.

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92103
      • Clinical Teaching Facility (CTF B-403 at UCSD Medical Center)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: TCT + PBO; 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; 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; Other Names: targeted cognitive training (TCT)
Active Comparator: TCT + MEM; 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; 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; Other Names: targeted cognitive training (TCT)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Positive & Negative Symptom Scale (PANSS) - Positive Symptom Subscale	Positive & Negative Symptom Scale (PANSS) positive symptom subscale measured at baseline vs. post-TCT session 10, 20 and 30 (approximately 16 weeks). The PANSS positive symptom subscale is rated from 1 to 7 points ranging from absent to extreme. The range for the Positive Symptom subscale is 7-49 and higher scores indicate 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).
Positive & Negative Symptom Scale (PANSS) - Negative Symptom Subscale	Positive & Negative Symptom Scale (PANSS) negative symptom subscale measured at baseline vs. post-TCT session 10, 20 and 30 (approximately 16 weeks). The PANSS negative symptom subscale is rated from 1 to 7 points ranging from absent to extreme. The range for the negative symptom subscale is 7-49 and higher scores indicate 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).
Psychotic Symptoms - PSYRATS Hallucination Subscale	Psychotic Symptom Rating Scales (PSYRATS hallucination subscale) measured at baseline vs. post-TCT session 10, 20 and 30 (approximately 16 weeks). The PSYRATS auditory hallucinations subscale (AHS) consisting of 11 items, with each item being rated from 0 (absent) to 4 (severe), range 0-44, with higher scores indicating more severe auditory hallucinations or 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).
Manic Symptoms - Young Mania Rating Scale	Young Mania Rating Scale total score measured at baseline vs. post-TCT session 10, 20 and 30 (approximately 16 weeks). The range for the YMRS total score is 0-60, with higher scores indicating more severe manic symptoms or 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).
Current Depressive Symptoms - PHQ-9	Patient Health Questionnaire-9 (PHQ-9) total score measured at baseline vs. post-TCT session 10, 20 and 30 (approximately 16 weeks). The PHQ-9 has a range from 0 to 27 with higher scores indicating more severe depression or 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).

Collaborators and Investigators

• Sponsor: University of California, San Diego

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2021
• Primary Completion (Actual): March 30, 2025
• Study Completion (Actual): March 30, 2025

Study Registration Dates

• First Submitted: April 21, 2021
• First Submitted That Met QC Criteria: April 21, 2021
• First Posted (Actual): April 23, 2021

Study Record Updates

• Last Update Posted (Actual): May 18, 2026
• Last Update Submitted That Met QC Criteria: April 24, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: schizophrenia; EEG; cognitive training
• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Schizophrenia; Psychotic Disorders; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Adamantane; Bridged-Ring Compounds; Amantadine; Memantine
• Other Study ID Numbers: 201502

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to share individual participant data with other researchers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes