Clinical trial NCT01459029: High Dose D-Serine as Adjuvant Treatment for Recent Onset Schizophrenia
Official title: High Dose D-Serine as Adjuvant Treatment for Recent Onset Schizophrenia : A Randomized, Double-Blind, Placebo-Controlled Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Schizophrenia
Keywords: Schizophrenia
NMDA receptor
D-serine
Recent onset
Negative symptoms
Cognition
Lead sponsor: Hadassah Medical Organization
Sponsor class: OTHER
Collaborators: name: Herzog Hospital
First posted: 2011-10-25
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from Baseline in the Total Score of the Positive and Negative Syndrome Scale (PANSS)
timeFrame: Biweekly for 12 weeks
Secondary outcomes:
measure: Change from Baseline in the Composite T-score of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Battery
timeFrame: 12 weeks
measure: Change from Baseline in the Subscales of PANSS
timeFrame: Biweekly for 12 weeks
measure: Change from Baseline in the Clinical Global Impressions (CGI)
timeFrame: Biweekly for 12 weeks
measure: Change from Baseline in the Scale for the Assessment of Negative Symptoms (SANS)
timeFrame: Biweekly for 12 weeks
measure: Change from Baseline in the Calgary Depression Scale for Schizophrenia (CDSS
timeFrame: Biweekly for 12 weeks
measure: Change from Baseline in the Quality of Life Scale (QOL)
timeFrame: Biweekly for 12 weeks
measure: Change from Baseline in the Simpson-Angus Extrapyramidal Rating Scale (SAS)
timeFrame: Biweekly for 12 weeks
measure: Change from Baseline in the Abnormal Involuntary Movement Scale (AIMS)
timeFrame: Biweekly for 12 weeks
measure: Change from Baseline in the Udvalg for Kliniske Undersgelser (UKU) Side Effect Rating Scale
timeFrame: Biweekly for 12 weeks
measure: Change from Baseline in the Prepulse Inhibition (PPI) of Startle
timeFrame: 12 weeks
measure: Amino Acid Serum Levels
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Jerusalem
country: Israel
facility: Ezrath Nashim - Herzog Memorial Hospital & Community Clinics
city: Jerusalem
country: Israel
facility: Hadassah Medical Organization
Study officials:
affiliation: Hadassah Medical Organization
name: Amit Lotan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hadassah Medical Organization
name: Bernard Lerer, MD
role: STUDY_DIRECTOR
affiliation: Ezrath Nashim - Herzog Memorial Hospital
name: Uriel Heresco-Levy, MD
role: STUDY_DIRECTOR
References: