High Dose D-Serine as Adjuvant Treatment for Recent Onset Schizophrenia

NCT ID: NCT01459029

Last Updated: 2011-10-25

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2014-10-31

Brief Summary

The purpose of this study is to compare efficacy and safety of add-on treatment with a moderately high dose of D-serine, an NMDA-glycine site agonist, in young, recent onset schizophrenia patients who suffer from significant symptoms despite treatment with antipsychotics.

Detailed Description

Background: Recent advances in understanding the neurobiology underlying schizophrenia have underscored a pivotal role for a specific receptor for the neurotransmitter glutamate, the NMDA receptor, whose function may be impaired in the disorder. Enhancing transmission at the NMDA receptor may therefore provide a novel mechanism for treating schizophrenia. Over the past decade clinical trials that included supplementation with different compounds enhancing transmission at the NMDA receptor have provided positive results, particularly with D-serine. However, none of these trials focused specifically on young patients with recent onset schizophrenia. In addition, the optimal D-serine dose was not determined, although a preliminary report suggested that higher doses than those used in most studies may provide additional benefit, without significant safety concerns or side effects. Also, the pro-cognitive effects of D-serine were not systematically analyzed, although preliminary data supports a potential role for D-serine in ameliorating the cognitive deficits found in schizophrenia.

Research Design: Over a two year period, 54 patients, male or female, aged 18-30 years who fulfill DSM-IV criteria for schizophrenia or schizoaffective disorder, will be entered into a 12 week, parallel group, double blind, randomized controlled trial assessing the efficacy of placebo vs. DSR (up to 6000 mg/day) augmentation to standard antipsychotic therapy. First episode patients, and patients treated with clozapine, will be randomized separately. Patients will be entered into the trial in accordance with strict inclusion and exclusion criteria after the nature of the study has been explained to them and they have given written informed consent. Clinical evaluations will be performed at baseline and then at regular intervals during the trial. In addition, neurocognitive evaluations, electrophysiological assessments and determination of amino acids levels will be conducted at the beginning and end of the study. Treatment emergent adverse effects will be monitored.

Conditions

Schizophrenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

D-serine

D-serine up to 6000 mg/day subject to tolerability

Group Type: ACTIVE_COMPARATOR

D-serine

Intervention Type: DRUG

Adjuvant treatment with D-serine up to 6000 mg/day vs. placebo

Control

Treatment with inert capsules (placebo)

Group Type: PLACEBO_COMPARATOR

D-serine

Intervention Type: DRUG

Adjuvant treatment with D-serine up to 6000 mg/day vs. placebo

Interventions

D-serine

Adjuvant treatment with D-serine up to 6000 mg/day vs. placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age 18-30
• Diagnosis of schizophrenia/schizoaffective disorder
• Recent onset (up to five years since onset of positive symptoms)
• Stable dose antipsychotic treatment for at least 4 weeks
• Baseline PANSS total score of at least 70
• Baseline PANSS negative subscale score of at least 20
• Clinically stable (stable CGI score for two consecutive weeks)

Exclusion Criteria

• Criteria for other DSM-IV Axis I diagnoses are met
• Lifetime history of alcohol or substance dependence
• Alcohol or substance abuse within the past year
• Judged clinically to be at suicidal or homicidal risk
• Female patients who are pregnant or lactating.
• Patients with known intolerance to D-serine treatment
• Patients treated with ECT within 12 weeks prior to study entry
• Patients treated with TMS within 4 weeks prior to study entry
• Patients suffering from an unstable and/or untreated medical disorder
• Patients suffering from renal or hepatic dysfunction

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Herzog Hospital

OTHER

Sponsor Role: collaborator

Hadassah Medical Organization

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Amit Lotan, MD

Role: PRINCIPAL_INVESTIGATOR

Hadassah Medical Organization

Bernard Lerer, MD

Role: STUDY_DIRECTOR

Hadassah Medical Organization

Uriel Heresco-Levy, MD

Role: STUDY_DIRECTOR

Ezrath Nashim - Herzog Memorial Hospital

Locations

Ezrath Nashim - Herzog Memorial Hospital & Community Clinics

Jerusalem, , Israel

Hadassah Medical Organization

Jerusalem, , Israel

Countries

Israel

Central Contacts

Amit Lotan, MD

Role: CONTACT

amitlo@hadassah.org.il

00 972 2 6777184

Bernard Lerer, MD

Role: CONTACT

lerer@cc.huji.ac.il

00 972 2 6777185

Facility Contacts

Uriel Heresco-Levy, MD

Role: primary

heresco@md.huji.ac.il

00 972 2 5316906

Arik Tzukert, DMD

Role: primary

arik@hadassah.org.il

00 972 2 6776095

Hadas Lemberg, PhD

Role: backup

lhadas@hadassah.org.il

00 972 2 6777572

Other Identifiers

043211- HMO-CTIL

Identifier Type: -

Identifier Source: org_study_id