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: Recruiting
• 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 (Anticipated): 69
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Gregory A Light, Ph.D.; Phone Number: 619-543-2496; Email: glight@health.ucsd.edu
• Study Contact Backup: Name: Joyce Sprock, B.A.; Phone Number: 619-471-9455; Email: jsprock@health.ucsd.edu

Study Locations

• United States
  • California
    • San Diego, California, United States, 92103
      • Recruiting
      • Clinical Teaching Facility (CTF B-403 at UCSD Medical Center)
      • Contact: Joyce Sprock, B.A.; Phone Number: 619-543-7201; Email: EEGstudy@health.ucsd.edu

Participation Criteria

Eligibility Criteria

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

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; Suppressing active psychosis with antipsychotics benefits cognitive interventions for schizophrenia, but it is possible that drugs with pro-cognitive effects will specifically, and perhaps synergistically, augment the clinical benefits of cognitive therapies. A "proof of concept" for this approach is found in the use of the pro-extinction drugs to selectively enhance the impact of cognitive therapy for anxiety disorders. In this "proof of concept", a learning-based therapy is paired with a medication that enhances a brain mechanism (extinction) that is both 1) critical to that form of learning, and 2) known to be deficient in some anxiety disorders.	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; Suppressing active psychosis with antipsychotics benefits cognitive interventions for schizophrenia, but it is possible that drugs with pro-cognitive effects will specifically, and perhaps synergistically, augment the clinical benefits of cognitive therapies. A "proof of concept" for this approach is found in the use of the pro-extinction drugs to selectively enhance the impact of cognitive therapy for anxiety disorders. In this "proof of concept", a learning-based therapy is paired with a medication that enhances a brain mechanism (extinction) that is both 1) critical to that form of learning, and 2) known to be deficient in some anxiety disorders.	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
Sound Sweeps and perceptual learning	Change from baseline TCT performance	25 weeks
MCCB cognitive test performance	Change from baseline MCCB performance	25 weeks
Clinical symptoms	Change from baseline clinical symptoms	25 weeks

Collaborators and Investigators

• Sponsor: University of California, San Diego

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2021
• Primary Completion (Anticipated): September 30, 2023
• Study Completion (Anticipated): December 30, 2023

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): March 24, 2023
• Last Update Submitted That Met QC Criteria: March 21, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: schizophrenia; EEG; cognitive training
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Psychotic Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; 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