D-serine Monotherapy for Schizophrenia

NCT00816894 | Completed Phase 2 DMC

• 2 other identifiers: Heresco CTIL147-0820080201
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (2)

• PANSS change scores.

  ~ biweekly throughout the study

• side effects

  ~ biweekly throughout the study

Secondary Outcomes (1)

• % treatment responders

  End of the study

Study Arms (2)

D-serine arm

EXPERIMENTAL

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.

Drug: D-serine

Olanzapine arm

ACTIVE COMPARATOR

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.

Drug: Olanzapine

Interventions

D-serine 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

Also known as: DSR

D-serine arm

Olanzapine 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.

Also known as: Zyprexa

Olanzapine arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-70;
• Diagnosis of schizophrenia/schizoaffective disorder according to DSM-IV criteria.
• Stable dose antipsychotic treatment for at least 4 weeks;
• Treatment refractoriness according to Kane et al.(1988) criteria.

You may not qualify if:

• Meeting criteria for other DSM-IV Axis I diagnoses ;
• Substance abuse or alcoholism during entire lifetime;
• Are judged clinically to be at suicidal or homicidal risk;
• 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;
• 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);
• Patients treated with depot antipsychotics or ECT within the eight weeks prior to study entry.

Sponsors & Collaborators

• Herzog Hospital: lead
• Israel Science Foundation: collaborator

Study Sites (1)

Ezrath Nashim - Herzog Memorial Hospital

Jerusalem, 91035, Israel

Location

MeSH Terms

Conditions

Schizophrenia

Interventions

Olanzapine

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Princepal Investigator

Study Record Dates

• First Submitted: January 1, 2009
• First Posted: January 5, 2009
• Study Start: January 1, 2009
• Primary Completion: February 1, 2013
• Study Completion: February 1, 2013
• Last Updated: December 10, 2013

Record last verified: 2013-12

Locations

IL (1)