Clinical trial NCT00816894: D-serine Monotherapy for Schizophrenia
Official title: D-serine Antipsychotic Monotherapy for Treatment Refractory Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Schizophrenia
Keywords: schizophrenia
treatment resistance
D-serine
Olanzapine
treatment refractory schizophrenia
Lead sponsor: Herzog Hospital
Sponsor class: OTHER
Collaborators: name: Israel Science Foundation
First posted: 2009-01-05
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: PANSS change scores.
timeFrame: ~ biweekly throughout the study
measure: side effects
timeFrame: ~ biweekly throughout the study
Secondary outcomes:
measure: % treatment responders
timeFrame: End of the study
Other outcomes:
Locations:
city: Jerusalem
country: Israel
facility: Ezrath Nashim - Herzog Memorial Hospital
Study officials:
References: