Biomarker Study of Acamprosate in Schizophrenia

This study has been completed.
Sponsor:
Collaborators:
National Alliance for Research on Schizophrenia and Depression
Information provided by (Responsible Party):
Bernard Fischer, MD, University of Maryland
ClinicalTrials.gov Identifier:
NCT00688324
First received: May 28, 2008
Last updated: September 10, 2012
Last verified: September 2012
  Purpose

NMDA receptors are brain receptors that are stimulated by glutamate. Poorly functioning NMDA receptors are thought to be involved in the pathology of schizophrenia. This hypothesis is based on the observation that PCP, which blocks the NMDA receptor, produces symptoms and cognitive impairments similar to schizophrenia. Efforts to enhance the function of the NMDA receptor with glycine and D-cycloserine have met with limited success. An alternative approach would be to use the drug acamprosate.

Acamprosate, FDA-approved for maintenance of sobriety after detoxification from alcohol, seems to act through modulation of the NMDA receptor. In the lab, acamprosate has been noted to act as an antagonist when the NMDA receptors are maximally stimulated but as an agonist when NMDA receptor stimulation is minimal. This "smart drug" action makes acamprosate appealing for use in schizophrenia. If acamprosate works as a smart drug in patients, then we would predict that it would enhance the function of NMDA receptors in schizophrenia and improve cognition and the symptoms of the illness. Additionally, acamprosate seems to modulate the NMDA receptor in novel ways distinct from glycine and D-cycloserine.

We will also see if the response to acamprosate differs based on whether participants do or do not have a past history of alcohol use disorders.


Condition Intervention Phase
Schizophrenia
Schizoaffective Disorder
Drug: Acamprosate
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Biomarker Study of Acamprosate in Schizophrenia

Resource links provided by NLM:


Further study details as provided by University of Maryland:

Primary Outcome Measures:
  • Levels of Glu&Gln, GABA, NAA in select brain regions [ Time Frame: Baseline and after 2 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Cognitive Test Performance [ Time Frame: Baseline and after 2 weeks ] [ Designated as safety issue: Yes ]
  • Symptom measures [ Time Frame: Baseline and after 2 weeks ] [ Designated as safety issue: Yes ]
  • Side-Effect Measures (Including Movement Side-Effects) [ Time Frame: Baseline and after 2 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 39
Study Start Date: June 2008
Study Completion Date: February 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single Arm
All subjects will have baseline measures, receive acamprosate for 2 weeks, then have measures repeated.
Drug: Acamprosate
Acamprosate 333mg, ii tablets PO tid x 2 weeks
Other Name: Campral

Detailed Description:

We propose to measure the response of symptoms and cognition in people schizophrenia given acamprosate or placebo. We hypothesize that symptoms and cognition will improve following two weeks of acamprosate. We will also use proton magnetic resonance spectroscopy (MRS) to examine the effect of acamprosate on glutamate & glutamine (Glu&Gln) brain levels in people with schizophrenia. We hypothesize that Glu&Gln concentrations in people with chronic schizophrenia will increase following two weeks of treatment with acamprosate.

The proposed study will consist of 50 individuals with chronic schizophrenia/schizoaffective disorder, 18-55 years old, from in/outpatient programs at the Maryland Psychiatric Research Center (MPRC). The dose of acamprosate will follow manufacturer recommendations with two 333mg tablets given three times per day. MRS will be acquired from areas involved in schizophrenia [dorsolateral-prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC)] at baseline and week two. Symptom ratings and cognitive testing will occur at baseline and be repeated at week two.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • DSM-IV diagnosis of schizophrenia/schizoaffective disorder
  • Age 18-55 years
  • Male or female
  • Any Race/ethnicity
  • Participants will be analyzed separately depending on whether they do or do not have a history of an alcohol use disorder

Exclusion Criteria:

  • Pregnant/nursing females or females not using adequate birth control
  • Documented history of mental retardation/severe neurological disorder/head injury with loss of consciousness
  • DSM-IV diagnosis of substance dependence in previous six months/abuse in the previous three months (except nicotine)
  • Serious suicidal risk in the previous six months
  • History of renal failure/creatinine clearance of less than 50mL/min
  • Current treatment with clozapine
  • Contraindication to MRI scanning.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00688324

Locations
United States, Maryland
Maryland Psychiatric Research Center
Baltimore, Maryland, United States, 21228
Keypoint Community Mental Health Centers- Catonsville
Baltimore, Maryland, United States, 21228
Keypoint Community Mental Health Centers- Dundalk
Baltimore, Maryland, United States, 21222
VA Maryland Health Care System
Baltimore, Maryland, United States, 21201
Sponsors and Collaborators
University of Maryland
National Alliance for Research on Schizophrenia and Depression
Investigators
Principal Investigator: Bernard A Fischer, M.D. University of Maryland
  More Information

Additional Information:
No publications provided

Responsible Party: Bernard Fischer, MD, Physician, Maryland Psychiatric Research Center, Outpatient Research Program, University of Maryland
ClinicalTrials.gov Identifier: NCT00688324     History of Changes
Other Study ID Numbers: HP-00043248, R03AA019571
Study First Received: May 28, 2008
Last Updated: September 10, 2012
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by University of Maryland:
schizophrenia
schizoaffective disorder
glutamate
NMDA receptor
magnetic resonance spectroscopy
acamprosate

Additional relevant MeSH terms:
Psychotic Disorders
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Acamprosate
Alcohol Deterrents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014