D-serine Monotherapy for Schizophrenia
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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 |
- 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 ]
- % treatment responders [ Time Frame: End of the study ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 60 |
| Study Start Date: | January 2009 |
| Estimated Study Completion Date: | December 2013 |
| Estimated Primary Completion Date: | December 2012 (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 |
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Contacts and Locations| Contact: Uriel Heresco-Levy, M.D. | 972-2-5316906 | heresco@md.huji.ac.il |
| Israel | |
| Ezrath Nashim - Herzog Memorial Hospital | Recruiting |
| Jerusalem, Israel, 91035 | |
| Contact: Uriel Heresco-Levy 972-2-5316906 heresco@md.huji.ac.il | |
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: | July 5, 2012 |
| 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 Antipsychotic Agents Tranquilizing Agents Central Nervous System Depressants Physiological Effects of Drugs Pharmacologic Actions Central Nervous System Agents Therapeutic Uses |
Psychotropic Drugs Serotonin Uptake Inhibitors Neurotransmitter Uptake Inhibitors Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Serotonin Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Gastrointestinal Agents |
ClinicalTrials.gov processed this record on May 19, 2013