Biomarker Strategies for Medication-Enhanced Cognitive Training in Schizophrenia (Swerdlow-R34)

September 30, 2022 updated by: Neal R. Swerdlow, M.D., Ph.D., University of California, San Diego
Cognitive training is moderately effective at reducing symptoms and improving life function in schizophrenia patients. The present application develops a strategy for increasing the effectiveness of cognitive training through the use of pro-cognitive medications. Specific biomarkers will be studied that identify patients most sensitive to these pro-cognitive medications, to test the feasibility of using these biomarkers in a large clinical trial of medication-enhanced cognitive training in schizophrenia.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This R34 application responds to PAR-09-173, to achieve the first goal of this FOA by supporting: "the development and/or pilot testing of new or adapted interventions." The two overarching goals of this application are: 1) to test the effects of the acute administration of the NMDA antagonist, memantine (MEM), on sensorimotor gating and working memory (WM) in schizophrenia (SZ) patients, and 2) to assess the feasibility of using MEM to predictably enhance the therapeutic benefits of cognitive training in SZ.

The pharmacotherapy of SZ has been dominated by antidopaminergic drugs with limited clinical impact. Some forms of psychosocial rehabilitation, such as cognitive training (CT), appear to effectively reduce symptoms and improve function in SZ. The premise of this application is that the benefits of CT in SZ might be enhanced by drugs that increase specific cognitive abilities, including WM, even if these pro-cognitive drugs lack clinical impact when administered without CT. The main goal of this application is to develop an innovative intervention strategy that enhances the clinical benefits of CT in SZ through administration of a pro-cognitive agent to biomarker-identified sensitive patients.

The investigators reported that a single dose of the widely used Alzheimer's disease medication, MEM (20 mg p.o.), significantly increased prepulse inhibition (PPI) of the startle reflex in healthy subjects. PPI-enhancing effects of MEM in healthy subjects are associated with: 1) increased WM; and 2) phenotypes linked to the high activity Val158Met COMT polymorphism. PPI is consistently impaired in SZ patients; lowest levels of PPI in patients are associated with: 1) poor functional outcome; and 2) the Val/Val COMT genotype. If our MEM findings in healthy subjects are reproduced in SZ patients, the investigators will detect MEM-associated improvements in PPI and WM, particularly among Val/Val patients. The investigators will then be positioned to test the hypothesis that acute PPI and WM-enhancing effects of MEM predict therapeutic benefit of MEM in SZ patients undergoing CT.

This application has two aims: Aim 1 will assess the acute effects of MEM (0 vs. 10 or 0 vs. 20 mg p.o.) in 60 SZ patients, to test the prediction that MEM will increase PPI and enhance WM in SZ patients, particularly in those characterized by low basal PPI levels and/or the Val/Val COMT genotype. Mismatch negativity and gamma band synchronization will also be assessed as potentially informative MEM-sensitive and functionally relevant biomarkers. Aim 2 will assess the feasibility of testing the therapeutic benefit of MEM as an adjunct to CT in SZ patients, and the feasibility of testing the primary hypothesis that such benefit will be predicted by increased PPI and/or WM in SZ patients after the Aim 1 single dose MEM challenge. It is predicted that subject recruitment and completion in both arms of a controlled 12-week CT trial in SZ out-patients among subjects completing Aim 1 will be appropriate for testing both the overall effectiveness of MEM as an adjunct to CT and the ability to predict this effectiveness among biomarker-identified patient subgroups.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
80

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Diego, California, United States, 92103
        • University of California, San Diego

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • A diagnosis of schizophrenia or schizoaffective disorder - depressed type

Exclusion Criteria:

  • Age range,
  • Current alcohol or drug abuse

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Health Services Research
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Memantine/high
memantine 20 mg
Drug: Memantine
Each participant receives a single pill of placebo or active drug (memantine, 10 or 20 mg) and completes about 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week.
Other Names:
  • Namenda
Placebo Comparator: Placebo/high
placebo comparator for memantine 20 mg
Drug: Placebo
Each participant receives a single pill of placebo or active drug (memantine, 10 or 20 mg) and completes about 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week.
Active Comparator: Memantine/low
memantine 10 mg
Drug: Memantine
Each participant receives a single pill of placebo or active drug (memantine, 10 or 20 mg) and completes about 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week.
Other Names:
  • Namenda
Placebo Comparator: Placebo/low
placebo comparator for memantine 10 mg
Drug: Placebo
Each participant receives a single pill of placebo or active drug (memantine, 10 or 20 mg) and completes about 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Prepulse Inhibition
Time Frame: approx 45 minutes
Prepulse inhibition of the startle reflex is the automatic reduction in startle magnitude (assessed here by EMG of orbicularis oculi) when a startling stimulus (here a 40 ms 118 dB(A) noise burst; "PULSE") is preceded (here 10 - 120 msec) by a weak stimulus (here a 20 msec burst 16 dB over background "PREPULSE"). A %PPI metric is calculated based on the relative startle magnitude on (PREPULSE + PULSE) trials vs. PULSE alone trials. Possible maximal inhibition is 100%; there is no maximal "negative" value of inhibition. There is no clear "advantage" or "disadvantage" for lower or higher %PPI values, though on average, schizophrenia patients demonstrate lower % values compared to matched healthy subjects.
approx 45 minutes

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
MATRICS
Time Frame: approx 1 hour
MATRICS Consensus Cognitive Battery Performance: This is a standardized neurocognitive battery that assesses performance in 7 domains of neurocognition. Primary data are recorded based on normalized T-scores; a separate score is provided for each domain, and a Comprehensive score (Primary measure here) is also calculated across domains. Possible T-score range is 0 - 100; higher score reflects better performance.
approx 1 hour

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of California, San Diego

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 13, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 14, 2012

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 15, 2012

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 4, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 30, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NIMH-R34-MH093453-NS

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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