D-Serine Treatment of Negative Symptoms and Cognitive Deficits in Schizophrenia

NCT00237809 | Completed Phase 3 Results

• 2 other identifiers: 23594DF01-015
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 2

Brief Summary

This study is based on the hypothesis that by increasing N-methyl-D-aspartic acid (NMDA) receptor function in the brain and thereby increasing the capacity of the brain to both form new connections and strengthen existing connections, schizophrenic patients may derive both greater and sustained benefit from cognitive retraining.

Conditions

Schizophrenia; Schizoaffective Disorder

Outcome Measures

Primary Outcomes (4)

• Wisconsin Card Sorting Test (WCST)

  The WCST allows the clinician to speculate to the following "frontal" lobe functions: strategic planning, organized searching, utilizing environmental feedback to shift cognitive sets, directing behavior toward achieving a goal, and modulating impulsive responding. The test can be administered to those from 6.5 years to 89 years of age.The test takes approximately 12-20 minutes to carry out and generates a number of psychometric scores, including numbers, percentages, and percentiles of: categories achieved, trials, errors, and perseverative errors. Can be interpreted as: the greater the percentage, the greater the measured ability.

  12 weeks

• Hopkins Verbal Learning Test

  The Hopkins Verbal Learning Test is designed to assess verbal learning and memory (immediate recall, delayed recall, delayed recognition). The assessment takes approximately 5-10 minutes with a 25-minute delay to complete and 2 minutes to score. The greater the score, the greater the measured recall. The score ranges from 0 to 24.

  12 weeks

• Spatial Span- Total Score

  The Spatial Span subtest of the Wechsler Memory Scale can be used as an indicator of working memory and visuospatial processing. An increase in severity of impairment results in a decrease in Spatial Span Total Score. The range is 1 to 28.

  12 weeks

• Positive and Negative Syndrome Scale (PANSS)

  The PANSS is a handscored instrument. It uses 25 PANSS items organized into five scales: Negative, Positive, Dysphoric Mood, Activation, and Autistic Preoccupation. The PANSS is based on findings that schizophrenia comprises at least two distinct syndromes. The positive syndrome consists of productive symptoms, while the negative syndrome consists of deficit features. This distinction is useful when developing treatment plans because you can focus on the type of symptoms the patient is experiencing. It is also useful when studying the effects of medication (e.g., in clinical drug trials) because it allows you to determine which type of symptoms are being affected. PANSS Total score minimum = 30, maximum = 210. The greater the score, the greater the symptoms.

  12 weeks

Secondary Outcomes (3)

• Heinrichs-Carpenter Quality of Life Scale

  12 weeks

• Simpson-Angus Neurological Rating Scale

  12 weeks

• UCSD Performance-Based Skills Assessment (UPSA)

  12 weeks

Study Arms (4)

Drug and control CRT

EXPERIMENTAL

D-serine/control

Drug: D-serine; Behavioral: Cognitive Retraining Placebo

Drug and CRT

EXPERIMENTAL

D-serine/cog rehab

Drug: D-serine; Behavioral: Cognitive Retraining (CRT)

Placebo Drug and Placebo CRT

EXPERIMENTAL

Placebo/control

Drug: Placebo; Behavioral: Cognitive Retraining Placebo

Placebo Drug and CRT

EXPERIMENTAL

Placebo/cog rehab

Behavioral: Cognitive Retraining (CRT); Drug: Placebo

Interventions

D-serine DRUG

D-serine (30 mg/kg)

Drug and CRT; Drug and control CRT

Cognitive Retraining (CRT) BEHAVIORAL

Cognitive retraining therapy (CRT)

Drug and CRT; Placebo Drug and CRT

Placebo DRUG

Placebo D-serine Drug

Placebo Drug and CRT; Placebo Drug and Placebo CRT

Cognitive Retraining Placebo BEHAVIORAL

Cognitive retraining therapy (CRT) control

Drug and control CRT; Placebo Drug and Placebo CRT

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of schizophrenia or schizoaffective disorder

You may not qualify if:

• Pregnant or lactating

Sponsors & Collaborators

• Yale University: lead
• National Alliance for Research on Schizophrenia and Depression: collaborator
• Donaghue Medical Research Foundation: collaborator

Study Sites (2)

Connecticut Mental Health Center

New Haven, Connecticut, 06508, United States

Location

VA Connecticut Healthcare System

West Haven, Connecticut, 06516, United States

Location

Related Publications (3)

• Tsai GE, Yang P, Chung LC, Tsai IC, Tsai CW, Coyle JT. D-serine added to clozapine for the treatment of schizophrenia. Am J Psychiatry. 1999 Nov;156(11):1822-5. doi: 10.1176/ajp.156.11.1822.

  PMID: 10553752 BACKGROUND

• Tsai G, Yang P, Chung LC, Lange N, Coyle JT. D-serine added to antipsychotics for the treatment of schizophrenia. Biol Psychiatry. 1998 Dec 1;44(11):1081-9. doi: 10.1016/s0006-3223(98)00279-0.

  PMID: 9836012 BACKGROUND

• Heresco-Levy U, Javitt DC, Ebstein R, Vass A, Lichtenberg P, Bar G, Catinari S, Ermilov M. D-serine efficacy as add-on pharmacotherapy to risperidone and olanzapine for treatment-refractory schizophrenia. Biol Psychiatry. 2005 Mar 15;57(6):577-85. doi: 10.1016/j.biopsych.2004.12.037.

  PMID: 15780844 BACKGROUND

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Results Point of Contact

• Title: Dr. Deepak Cyril D'Souza
• Organization: Yale University

deepak.dsouza@yale.edu

203-932-5711

Study Officials

• Deepak C D'Souza, M.D.

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: September 13, 2005
• First Posted: October 12, 2005
• Study Start: September 1, 2002
• Primary Completion: December 1, 2010
• Study Completion: September 1, 2012
• Last Updated: May 10, 2017
• Results First Posted: May 10, 2017

Record last verified: 2017-03

Locations

US (2)