D-serine Monotherapy for Schizophrenia

This study has been completed.
Sponsor:
Collaborator:
Israel Science Foundation
Information provided by (Responsible Party):
Heresco-Levi Uriel, Herzog Hospital
ClinicalTrials.gov Identifier:
NCT00816894
First received: January 1, 2009
Last updated: December 9, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Schizophrenia
Drug: D-serine
Drug: Olanzapine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: D-serine Antipsychotic Monotherapy for Treatment Refractory Schizophrenia

Resource links provided by NLM:


Further study details as provided by Herzog Hospital:

Primary Outcome Measures:
  • PANSS change scores. [ Time Frame: ~ biweekly throughout the study ] [ Designated as safety issue: No ]
  • side effects [ Time Frame: ~ biweekly throughout the study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • % treatment responders [ Time Frame: End of the study ] [ Designated as safety issue: No ]

Enrollment: 18
Study Start Date: January 2009
Study Completion Date: February 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: 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
Other Name: DSR
Active Comparator: 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.
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.
Other Name: Zyprexa

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00816894

Locations
Israel
Ezrath Nashim - Herzog Memorial Hospital
Jerusalem, Israel, 91035
Sponsors and Collaborators
Herzog Hospital
Israel Science Foundation
  More Information

No publications provided

Responsible Party: Heresco-Levi Uriel, Princepal Investigator, Herzog Hospital
ClinicalTrials.gov Identifier: NCT00816894     History of Changes
Other Study ID Numbers: Heresco CTIL147-08, 20080201
Study First Received: January 1, 2009
Last Updated: December 9, 2013
Health Authority: Israel: Israeli Health Ministry Pharmaceutical Administration

Keywords provided by Herzog Hospital:
schizophrenia
treatment resistance
D-serine
Olanzapine
treatment refractory schizophrenia

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Olanzapine
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Gastrointestinal Agents
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin Agents

ClinicalTrials.gov processed this record on September 22, 2014