Memantine for the Prevention of Cognitive Dysfunction and Negative Symptoms in Patients With Acute Schizophrenia

Sponsor

M. Schaefer, MD (Other)

Overall Status

Terminated

CT.gov ID

NCT00148590

Collaborator

Stanley Medical Research Institute (Other)

Enrollment

Location

Arms

Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of a 6 weeks memantine add-on to risperidon treatment for the prevention of cognitive dysfunction and negative symptomatology in patients with acute schizophrenia.

Psychopathological changes were assessed with the Positive and Negative Syndrome Scale (PANSS) at baseline and after 2, 4, 6, 12, and 24 weeks. Cognitive function were measured at baseline and week 6, and 24 by the California Verbal Learning Test, Benton Learning Test, Digit Span Forward and Backward Test, Continuous Performance Test, Stroop Test, Trail-Making Test, Verbal Fluency Test, and Wisconsin Card Sorting Test.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: Memantine Drug: Placebo	Phase 3

Detailed Description

This study examines the efficacy and safety of a 6 weeks memantine add-on to risperidon treatment for the prevention of cognitive dysfunction and negative symptomatology in patients with acute schizophrenia. The trail is double-blind, prospective, randomized, placebo-controlled, parallel-group and consisting of a 'placebo-run-in' period, treatment, and follow-up periods. Study personnel and participants were blinded to group assignment. In the 'run-in' period, patients received Lorazepam for the treatment of anxiety and tension states for two weeks before starting antipsychotic therapy. After the 'run-in' period treatment, patients began receiving antipsychotic therapy with Risperidon with continuous concomitant administration of Memantine, 20 mg/d, or placebo for six weeks. Adherence was assessed at each clinic visit by pill count. In cases of anxiety and tension states, an experienced psychiatrist decided whether patients should receive Lorazepam, 5 mg/d, as rescue medication in addition to the study medication (Memantine or placebo), to which the patients remained blinded. In cases of pseudo parkinsonism patients were allowed to receive Biperiden, up to 8 mg/d, and for the treatment of patients suffering from sleep disorders Zopiclon (15 mg/d) was allowed. The consumption of alcohol and drugs were not allowed during the trial. In both study parts, psychiatric assessments were performed at baseline as well as after 2; 4; 6; 12 and 24 weeks after treatment (that is, during the follow-up period). The neuropsychological examination was performed at baseline, and after 6 and 24 weeks. Psychiatric changes, adverse events, laboratory values, dose adjustments of the antipsychotic therapy, and possible pharmacologic adverse effects were systematically monitored throughout the study.

Study Design

Study Type:

Interventional

Actual Enrollment :

24 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Prevention

Official Title:

Memantine add-on to Risperidon for Treatment of Negative Symptoms and Cognitive Dysfunction in Patients With Acute Schizophrenia: Results of a Proof of Concept Study

Study Start Date :

Nov 1, 2005

Actual Primary Completion Date :

Jun 1, 2008

Actual Study Completion Date :

Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Memantine plus Risperidone 6 weeks 20 mg Memantine as add-on treatment to Risperidone	Drug: Memantine Daily dose of 20 mg Memantine add-on to Risperidone vs Placebo add-on to Risperidone Other Names: Akatinol
Placebo Comparator: Placebo plus Risperidone 6 weeks 20 mg Placebo as add-on treatment to Risperidone	Drug: Placebo Daily dose of 20 mg Memantine add-on to Risperidone vs Placebo add-on to Risperidone

Arm

Intervention/Treatment

Active Comparator: Memantine plus Risperidone

6 weeks 20 mg Memantine as add-on treatment to Risperidone

Drug: Memantine

Daily dose of 20 mg Memantine add-on to Risperidone vs Placebo add-on to Risperidone

Other Names:

Akatinol

Placebo Comparator: Placebo plus Risperidone

6 weeks 20 mg Placebo as add-on treatment to Risperidone

Drug: Placebo

Daily dose of 20 mg Memantine add-on to Risperidone vs Placebo add-on to Risperidone

Outcome Measures

Primary Outcome Measures

Changes in PANSS negative subscore between memantine and placebo treatment [during trial]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 40 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosis of schizophrenia (DSM-IV)
Age 18 to 40
Exacerbation of an acute schizophrenic episode (PANSS positive score > 20)
At least one previous schizophrenic episode
Informed consent
Subjects must be considered by the investigator to be compliant
Subjects must have an educational level and a degree of understanding such that they can meaningfully communicate with the investigator

Exclusion Criteria:

Axis I disorder other than schizophrenia within 12 months, e.g. schizoaffective disorder
Severe negative symptomatology (PANNS negative score >20 points)
Duration of schizophrenia > 5 years
Dependency on alcohol or addictive drugs within 6 months of the baseline evaluation
Contraindication of risperidone
Significant neurological, cardiovascular, hepatic, renal, metabolic, or other medical diseases or any clinically relevant abnormalities in laboratory tests
Prior ECT-treatment, metal implantations
Female subjects during pregnancy and breastfeeding
Female subjects within childbearing years who were not using adequate birth control
Patients who are judged by the investigator to be at serious suicide risk

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Charité Universitaetsmedizin Berlin; Campus Charité Mitte; Dept. for Psychiatry and Psychotherapy	Berlin		Germany	10117

Sponsors and Collaborators

M. Schaefer, MD
Stanley Medical Research Institute

Investigators

Principal Investigator: Martin Schaefer, MD, Charite Campus Mitte; Dept. of Psychiatry and Psychotherapy and Department of Psychiatry, Kliniken Essen-Mitte, Essen