D-serine Monotherapy for Schizophrenia

Schizophrenia Clinical Trial

Official title:

D-serine Antipsychotic Monotherapy for Treatment Refractory Schizophrenia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00816894
• Other study ID #: Heresco CTIL147-08
• Secondary ID: 20080201
• Status: Completed
• Phase: Phase 2
• First received: January 1, 2009
• Last updated: December 9, 2013
• Start date: January 2009
• Est. completion date: February 2013

Study information

• Verified date: December 2013
• Source: Herzog Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Israeli Health Ministry Pharmaceutical Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: February 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Schizophrenia

Intervention

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
• 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.

Locations

Country	Name	City	State
Israel	Ezrath Nashim - Herzog Memorial Hospital	Jerusalem

Sponsors (2)

Lead Sponsor	Collaborator
Herzog Hospital	Israel Science Foundation

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PANSS change scores.		~ biweekly throughout the study	No
Primary	side effects		~ biweekly throughout the study	Yes
Secondary	% treatment responders		End of the study	No