D-serine Monotherapy for Schizophrenia

NCT ID: NCT00816894

Last Updated: 2013-12-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-01-31
• Study Completion Date: 2013-02-28

Brief Summary

A first generation of clinical studies, performed during the last decade, demonstrates that adjuvant treatment with compounds that enhance NMDAR-mediated neurotransmission due to their agonistic activity at the NMDAR-associated glycine (GLY) site (e.g. GLY, D-serine (DSR)) leads to significant symptom reductions in chronic schizophrenia patients.Furthermore, preliminary findings suggest that treatment with NMDAR-GLY site modulators may also be beneficial as antipsychotic monotherapy In the proposed project, during a three year period, 60 schizophrenia patients that fulfill treatment resistance criteria will be randomly entered in a 10 week, two phase (fixed/flexible dose), parallel group, double blind controlled study assessing the efficacy of olanzapine (OLA) (up to 40 mg/day) vs. DSR (up to 4000 mg/day) as antipsychotic monotherapy.Clinical, neurocognitive, electrophysiological, and amino acids (i.e. GLY, DSR) levels assessments will be performed during the study. The specific aims of the proposed project are: 1) to assess the efficacy and safety of DSR as a new medication for treatment refractory schizophrenia, and 2) to assess DSR effects in terms of relevant amino acids serum levels, neurocognitive performance, and relevant brain electrophysiological parameters. The overall importance of the proposed project consists of its potential to lay the foundations for an innovative type of intervention for treatment resistant schizophrenia patients.

Conditions

Schizophrenia

Keywords

schizophrenia; treatment resistance; D-serine; Olanzapine; treatment refractory schizophrenia

Study Design

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

Study Groups

D-serine arm

6 week fixed dose phase with D-serine 1500 mg/day to be increased starting from week two to 3000 mg/day followed by a 4 week flexible dose phase allowing for two 500 mg/day dose changes.

Group Type: EXPERIMENTAL

D-serine

Intervention Type: DRUG

6 week fixed dose phase with D-serine 1500 mg/day to be increased starting from week two to 3000 mg/day followed by a 4 week flexible dose phase allowing for two 500 mg/day dose changes

Olanzapine arm

6 week fixed dose phase with Olanzapine 15 mg/day to be increased starting from week two to 30 mg/day followed by a 4 week flexible dose phase allowing for two 5 mg/day dose changes.

Group Type: ACTIVE_COMPARATOR

Olanzapine

Intervention Type: DRUG

6 week fixed dose phase with Olanzapine 15 mg/day to be increased starting from week two to 30 mg/day followed by a 4 week flexible dose phase allowing for two 5 mg/day dose changes.

Interventions

D-serine

6 week fixed dose phase with D-serine 1500 mg/day to be increased starting from week two to 3000 mg/day followed by a 4 week flexible dose phase allowing for two 500 mg/day dose changes

Intervention Type: DRUG

Olanzapine

6 week fixed dose phase with Olanzapine 15 mg/day to be increased starting from week two to 30 mg/day followed by a 4 week flexible dose phase allowing for two 5 mg/day dose changes.

Intervention Type: DRUG

Other Intervention Names

DSR; Zyprexa

Eligibility Criteria

Inclusion Criteria

1. Age 18-70;

2. Diagnosis of schizophrenia/schizoaffective disorder according to DSM-IV criteria.

3. Stable dose antipsychotic treatment for at least 4 weeks;

4. Treatment refractoriness according to Kane et al.(1988) criteria.

Exclusion Criteria

1. Meeting criteria for other DSM-IV Axis I diagnoses ;

2. Substance abuse or alcoholism during entire lifetime;

3. Are judged clinically to be at suicidal or homicidal risk;

4. Female patients who are pregnant or lactating; female patients who are not pregnant or lactating, if sexually active, must be using medically accepted means of contraception;

5. Patients with known intolerance to OLA treatment or who have failed an adequate trial of OLA (at least 6 weeks) at high doses (20 mg/day or higher);

6. Patients treated with depot antipsychotics or ECT within the eight weeks prior to study entry.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Israel Science Foundation

OTHER

Sponsor Role: collaborator

Herzog Hospital

OTHER

Sponsor Role: lead

Responsible Party

Heresco-Levi Uriel

Princepal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Ezrath Nashim - Herzog Memorial Hospital

Jerusalem, , Israel

Countries

Israel

Other Identifiers

20080201

Identifier Type: -

Identifier Source: secondary_id

Heresco CTIL147-08

Identifier Type: -

Identifier Source: org_study_id