High Dose D-Serine as Adjuvant Treatment for Recent Onset Schizophrenia (SATROS)
Primary Purpose
Schizophrenia
Status
Unknown status
Phase
Phase 2
Locations
Israel
Study Type
Interventional
Intervention
D-serine
Sponsored by
About this trial
This is an interventional treatment trial for Schizophrenia focused on measuring Schizophrenia, NMDA receptor, D-serine, Recent onset, Negative symptoms, Cognition
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
Sites / Locations
- Ezrath Nashim - Herzog Memorial Hospital & Community Clinics
- Hadassah Medical Organization
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
D-serine
Control
Arm Description
D-serine up to 6000 mg/day subject to tolerability
Treatment with inert capsules (placebo)
Outcomes
Primary Outcome Measures
Change from Baseline in the Total Score of the Positive and Negative Syndrome Scale (PANSS)
Secondary Outcome Measures
Change from Baseline in the Composite T-score of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Battery
Change from Baseline in the Subscales of PANSS
Change from Baseline in the Clinical Global Impressions (CGI)
Change from Baseline in the Scale for the Assessment of Negative Symptoms (SANS)
Change from Baseline in the Calgary Depression Scale for Schizophrenia (CDSS
Change from Baseline in the Quality of Life Scale (QOL)
Change from Baseline in the Simpson-Angus Extrapyramidal Rating Scale (SAS)
Change from Baseline in the Abnormal Involuntary Movement Scale (AIMS)
Change from Baseline in the Udvalg for Kliniske Undersgelser (UKU) Side Effect Rating Scale
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
Amino Acid Serum Levels
Glutamate, Glycine, D-serine
Full Information
NCT ID
NCT01459029
First Posted
October 9, 2011
Last Updated
October 24, 2011
Sponsor
Hadassah Medical Organization
Collaborators
Herzog Hospital
1. Study Identification
Unique Protocol Identification Number
NCT01459029
Brief Title
High Dose D-Serine as Adjuvant Treatment for Recent Onset Schizophrenia
Acronym
SATROS
Official Title
High Dose D-Serine as Adjuvant Treatment for Recent Onset Schizophrenia : A Randomized, Double-Blind, Placebo-Controlled Study
Study Type
Interventional
2. Study Status
Record Verification Date
October 2011
Overall Recruitment Status
Unknown status
Study Start Date
November 2011 (undefined)
Primary Completion Date
October 2013 (Anticipated)
Study Completion Date
October 2014 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hadassah Medical Organization
Collaborators
Herzog Hospital
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia
Keywords
Schizophrenia, NMDA receptor, D-serine, Recent onset, Negative symptoms, Cognition
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
54 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
D-serine
Arm Type
Active Comparator
Arm Description
D-serine up to 6000 mg/day subject to tolerability
Arm Title
Control
Arm Type
Placebo Comparator
Arm Description
Treatment with inert capsules (placebo)
Intervention Type
Drug
Intervention Name(s)
D-serine
Intervention Description
Adjuvant treatment with D-serine up to 6000 mg/day vs. placebo
Primary Outcome Measure Information:
Title
Change from Baseline in the Total Score of the Positive and Negative Syndrome Scale (PANSS)
Time Frame
Biweekly for 12 weeks
Secondary Outcome Measure Information:
Title
Change from Baseline in the Composite T-score of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Battery
Time Frame
12 weeks
Title
Change from Baseline in the Subscales of PANSS
Time Frame
Biweekly for 12 weeks
Title
Change from Baseline in the Clinical Global Impressions (CGI)
Time Frame
Biweekly for 12 weeks
Title
Change from Baseline in the Scale for the Assessment of Negative Symptoms (SANS)
Time Frame
Biweekly for 12 weeks
Title
Change from Baseline in the Calgary Depression Scale for Schizophrenia (CDSS
Time Frame
Biweekly for 12 weeks
Title
Change from Baseline in the Quality of Life Scale (QOL)
Time Frame
Biweekly for 12 weeks
Title
Change from Baseline in the Simpson-Angus Extrapyramidal Rating Scale (SAS)
Time Frame
Biweekly for 12 weeks
Title
Change from Baseline in the Abnormal Involuntary Movement Scale (AIMS)
Time Frame
Biweekly for 12 weeks
Title
Change from Baseline in the Udvalg for Kliniske Undersgelser (UKU) Side Effect Rating Scale
Time Frame
Biweekly for 12 weeks
Title
Change from Baseline in the Prepulse Inhibition (PPI) of Startle
Description
Patients with schizophrenia and their relatives may exhibit deficits in this operational measure of sensorimotor gating
Time Frame
12 weeks
Title
Amino Acid Serum Levels
Description
Glutamate, Glycine, D-serine
Time Frame
12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Amit Lotan, MD
Phone
00 972 2 6777184
Email
amitlo@hadassah.org.il
First Name & Middle Initial & Last Name or Official Title & Degree
Bernard Lerer, MD
Phone
00 972 2 6777185
Email
lerer@cc.huji.ac.il
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amit Lotan, MD
Organizational Affiliation
Hadassah Medical Organization
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Bernard Lerer, MD
Organizational Affiliation
Hadassah Medical Organization
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Uriel Heresco-Levy, MD
Organizational Affiliation
Ezrath Nashim - Herzog Memorial Hospital
Official's Role
Study Director
Facility Information:
Facility Name
Ezrath Nashim - Herzog Memorial Hospital & Community Clinics
City
Jerusalem
Country
Israel
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Uriel Heresco-Levy, MD
Phone
00 972 2 5316906
Email
heresco@md.huji.ac.il
First Name & Middle Initial & Last Name & Degree
Uriel Heresco-Levy, MD
First Name & Middle Initial & Last Name & Degree
Raz Levin
Facility Name
Hadassah Medical Organization
City
Jerusalem
Country
Israel
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Arik Tzukert, DMD
Phone
00 972 2 6776095
Email
arik@hadassah.org.il
First Name & Middle Initial & Last Name & Degree
Hadas Lemberg, PhD
Phone
00 972 2 6777572
Email
lhadas@hadassah.org.il
First Name & Middle Initial & Last Name & Degree
Amit Lotan, MD
First Name & Middle Initial & Last Name & Degree
Pablo Roitman, MD
First Name & Middle Initial & Last Name & Degree
Rina Cooper-Kazaz, MD
12. IPD Sharing Statement
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High Dose D-Serine as Adjuvant Treatment for Recent Onset Schizophrenia
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