High Dose D-Serine as Adjuvant Treatment for Recent Onset Schizophrenia

Schizophrenia Clinical Trial

— SATROS  

Official title:

High Dose D-Serine as Adjuvant Treatment for Recent Onset Schizophrenia : A Randomized, Double-Blind, Placebo-Controlled Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01459029
• Other study ID #: 043211- HMO-CTIL
• Status: Not yet recruiting
• Phase: Phase 2
• First received: October 9, 2011
• Last updated: October 24, 2011
• Start date: November 2011
• Est. completion date: October 2014

Study information

• Verified date: October 2011
• Source: Hadassah Medical Organization
• Contact: Amit Lotan, MD
• Phone: 00 972 2 6777184
• Email: amitlo[@]hadassah.org.il
• Is FDA regulated: No
• Health authority: Israel: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare efficacy and safety of add-on treatment with a moderately high dose of D-serine, an NMDA-glycine site agonist, in young, recent onset schizophrenia patients who suffer from significant symptoms despite treatment with antipsychotics.

Description:

Background: Recent advances in understanding the neurobiology underlying schizophrenia have underscored a pivotal role for a specific receptor for the neurotransmitter glutamate, the NMDA receptor, whose function may be impaired in the disorder. Enhancing transmission at the NMDA receptor may therefore provide a novel mechanism for treating schizophrenia. Over the past decade clinical trials that included supplementation with different compounds enhancing transmission at the NMDA receptor have provided positive results, particularly with D-serine. However, none of these trials focused specifically on young patients with recent onset schizophrenia. In addition, the optimal D-serine dose was not determined, although a preliminary report suggested that higher doses than those used in most studies may provide additional benefit, without significant safety concerns or side effects. Also, the pro-cognitive effects of D-serine were not systematically analyzed, although preliminary data supports a potential role for D-serine in ameliorating the cognitive deficits found in schizophrenia.

Research Design: Over a two year period, 54 patients, male or female, aged 18-30 years who fulfill DSM-IV criteria for schizophrenia or schizoaffective disorder, will be entered into a 12 week, parallel group, double blind, randomized controlled trial assessing the efficacy of placebo vs. DSR (up to 6000 mg/day) augmentation to standard antipsychotic therapy. First episode patients, and patients treated with clozapine, will be randomized separately. Patients will be entered into the trial in accordance with strict inclusion and exclusion criteria after the nature of the study has been explained to them and they have given written informed consent. Clinical evaluations will be performed at baseline and then at regular intervals during the trial. In addition, neurocognitive evaluations, electrophysiological assessments and determination of amino acids levels will be conducted at the beginning and end of the study. Treatment emergent adverse effects will be monitored.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 54
• Est. completion date: October 2014
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 30 Years

Eligibility

Inclusion Criteria:

• Age 18-30

• Diagnosis of schizophrenia/schizoaffective disorder

• Recent onset (up to five years since onset of positive symptoms)

• Stable dose antipsychotic treatment for at least 4 weeks

• Baseline PANSS total score of at least 70

• Baseline PANSS negative subscale score of at least 20

• Clinically stable (stable CGI score for two consecutive weeks)

Exclusion Criteria:

• Criteria for other DSM-IV Axis I diagnoses are met

• Lifetime history of alcohol or substance dependence

• Alcohol or substance abuse within the past year

• Judged clinically to be at suicidal or homicidal risk

• Female patients who are pregnant or lactating.

• Patients with known intolerance to D-serine treatment

• Patients treated with ECT within 12 weeks prior to study entry

• Patients treated with TMS within 4 weeks prior to study entry

• Patients suffering from an unstable and/or untreated medical disorder

• Patients suffering from renal or hepatic dysfunction

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
Adjuvant treatment with D-serine up to 6000 mg/day vs. placebo

Locations

Country	Name	City	State
Israel	Ezrath Nashim - Herzog Memorial Hospital & Community Clinics	Jerusalem
Israel	Hadassah Medical Organization	Jerusalem

Sponsors (2)

Lead Sponsor	Collaborator
Hadassah Medical Organization	Herzog Hospital

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline in the Total Score of the Positive and Negative Syndrome Scale (PANSS)		Biweekly for 12 weeks	No
Secondary	Change from Baseline in the Composite T-score of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Battery		12 weeks	No
Secondary	Change from Baseline in the Subscales of PANSS		Biweekly for 12 weeks	No
Secondary	Change from Baseline in the Clinical Global Impressions (CGI)		Biweekly for 12 weeks	No
Secondary	Change from Baseline in the Scale for the Assessment of Negative Symptoms (SANS)		Biweekly for 12 weeks	No
Secondary	Change from Baseline in the Calgary Depression Scale for Schizophrenia (CDSS		Biweekly for 12 weeks	No
Secondary	Change from Baseline in the Quality of Life Scale (QOL)		Biweekly for 12 weeks	No
Secondary	Change from Baseline in the Simpson-Angus Extrapyramidal Rating Scale (SAS)		Biweekly for 12 weeks	Yes
Secondary	Change from Baseline in the Abnormal Involuntary Movement Scale (AIMS)		Biweekly for 12 weeks	Yes
Secondary	Change from Baseline in the Udvalg for Kliniske Undersgelser (UKU) Side Effect Rating Scale		Biweekly for 12 weeks	Yes
Secondary	Change from Baseline in the Prepulse Inhibition (PPI) of Startle	Patients with schizophrenia and their relatives may exhibit deficits in this operational measure of sensorimotor gating	12 weeks	No
Secondary	Amino Acid Serum Levels	Glutamate, Glycine, D-serine	12 weeks	No