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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2012 by University of California, San Diego.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Neal R. Swerdlow, M.D., Ph.D., University of California, San Diego
ClinicalTrials.gov Identifier:
NCT01555697
First received: March 13, 2012
Last updated: March 14, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
Schizophrenia
Drug: Memantine
Drug: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Health Services Research
Official Title: Biomarker Strategies for Medication-Enhanced Cognitive Training in Schizophrenia

Resource links provided by NLM:


Further study details as provided by University of California, San Diego:

Primary Outcome Measures:
  • Prepulse inhibition [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Prepulse inhibition of the startle reflex


Secondary Outcome Measures:
  • MATRICS [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    MATRICS Consensus Cognitive Battery Performance


Estimated Enrollment: 60
Study Start Date: July 2011
Estimated Study Completion Date: March 2013
Estimated Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Memantine 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 Name: Namenda
Placebo Comparator: Placebo 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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • A diagnosis of schizophrenia or schizoaffective disorder - depressed type

Exclusion Criteria:

  • Age range,
  • Current alcohol or drug abuse
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01555697

Contacts
Contact: Jo Talledo, B.A. 619-543-3093 atalledo@ucsd.edu
Contact: Sarah N Lamb, B.A. 619-543-7840 snlamb@ucsd.edu

Locations
United States, California
University of California, San Diego Recruiting
San Diego, California, United States, 92103
Contact: Jo Talledo, B.A.    619-543-3093    atalledo@ucsd.edu   
Contact: Sarah N Lamb, B.A.    619-543-7840    snlamb@ucsd.edu   
Principal Investigator: Neal R Swerdlow, M.D., Ph.D.         
Sponsors and Collaborators
University of California, San Diego
  More Information

No publications provided

Responsible Party: Neal R. Swerdlow, M.D., Ph.D., Professor, University of California, San Diego
ClinicalTrials.gov Identifier: NCT01555697     History of Changes
Other Study ID Numbers: NIMH-R34-MH093453-NS
Study First Received: March 13, 2012
Last Updated: March 14, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, San Diego:
Schizophrenia
prepulse inhibition
neurocognition
working memory
memantine
MATRICS Consensus Cognitive Battery

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Memantine
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents

ClinicalTrials.gov processed this record on August 01, 2014