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

This study is not yet open for participant recruitment.
Verified October 2011 by Hadassah Medical Organization
Sponsor:
Collaborator:
Herzog Hospital
Information provided by (Responsible Party):
Hadassah Medical Organization
ClinicalTrials.gov Identifier:
NCT01459029
First received: October 9, 2011
Last updated: October 24, 2011
Last verified: October 2011
History of Changes
  Purpose

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.


Condition Intervention Phase
Schizophrenia
 Drug: D-serine
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: High Dose D-Serine as Adjuvant Treatment for Recent Onset Schizophrenia : A Randomized, Double-Blind, Placebo-Controlled Study

Resource links provided by NLM:

MedlinePlus related topics: Schizophrenia
Drug Information available for: Serine
U.S. FDA Resources

Further study details as provided by Hadassah Medical Organization:

Primary Outcome Measures:
  • Change from Baseline in the Total Score of the Positive and Negative Syndrome Scale (PANSS) [ Time Frame: Biweekly for 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Change from Baseline in the Subscales of PANSS [ Time Frame: Biweekly for 12 weeks ] [ Designated as safety issue: No ]
  • Change from Baseline in the Clinical Global Impressions (CGI) [ Time Frame: Biweekly for 12 weeks ] [ Designated as safety issue: No ]
  • Change from Baseline in the Scale for the Assessment of Negative Symptoms (SANS) [ Time Frame: Biweekly for 12 weeks ] [ Designated as safety issue: No ]
  • Change from Baseline in the Calgary Depression Scale for Schizophrenia (CDSS [ Time Frame: Biweekly for 12 weeks ] [ Designated as safety issue: No ]
  • Change from Baseline in the Quality of Life Scale (QOL) [ Time Frame: Biweekly for 12 weeks ] [ Designated as safety issue: No ]
  • Change from Baseline in the Simpson-Angus Extrapyramidal Rating Scale (SAS) [ Time Frame: Biweekly for 12 weeks ] [ Designated as safety issue: Yes ]
  • Change from Baseline in the Abnormal Involuntary Movement Scale (AIMS) [ Time Frame: Biweekly for 12 weeks ] [ Designated as safety issue: Yes ]
  • Change from Baseline in the Udvalg for Kliniske Undersgelser (UKU) Side Effect Rating Scale [ Time Frame: Biweekly for 12 weeks ] [ Designated as safety issue: Yes ]
  • Change from Baseline in the Prepulse Inhibition (PPI) of Startle [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Patients with schizophrenia and their relatives may exhibit deficits in this operational measure of sensorimotor gating

  • Amino Acid Serum Levels [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Glutamate, Glycine, D-serine


Estimated Enrollment: 54
Study Start Date: November 2011
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: D-serine
D-serine up to 6000 mg/day subject to tolerability
 Drug: D-serine
Adjuvant treatment with D-serine up to 6000 mg/day vs. placebo
Placebo Comparator: Control
Treatment with inert capsules (placebo)
 Drug: D-serine
Adjuvant treatment with D-serine up to 6000 mg/day vs. placebo

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

Ages Eligible for Study:   18 Years to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01459029

Contacts
Contact: Amit Lotan, MD 00 972 2 6777184 amitlo@hadassah.org.il
Contact: Bernard Lerer, MD 00 972 2 6777185 lerer@cc.huji.ac.il

Locations
Israel
Hadassah Medical Organization Not yet recruiting
Jerusalem, Israel
Contact: Arik Tzukert, DMD     00 972 2 6776095     arik@hadassah.org.il    
Contact: Hadas Lemberg, PhD     00 972 2 6777572     lhadas@hadassah.org.il    
Principal Investigator: Amit Lotan, MD            
Sub-Investigator: Pablo Roitman, MD            
Sub-Investigator: Rina Cooper-Kazaz, MD            
Ezrath Nashim - Herzog Memorial Hospital & Community Clinics Not yet recruiting
Jerusalem, Israel
Contact: Uriel Heresco-Levy, MD     00 972 2 5316906     heresco@md.huji.ac.il    
Principal Investigator: Uriel Heresco-Levy, MD            
Sub-Investigator: Raz Levin            
Sponsors and Collaborators
Hadassah Medical Organization
Herzog Hospital
Investigators
Principal Investigator: Amit Lotan, MD Hadassah Medical Organization
Study Director: Bernard Lerer, MD Hadassah Medical Organization
Study Director: Uriel Heresco-Levy, MD Ezrath Nashim - Herzog Memorial Hospital
  More Information

No publications provided

Responsible Party: Hadassah Medical Organization
ClinicalTrials.gov Identifier: NCT01459029     History of Changes
Other Study ID Numbers: 043211- HMO-CTIL
Study First Received: October 9, 2011
Last Updated: October 24, 2011
Health Authority: Israel: Ministry of Health

Keywords provided by Hadassah Medical Organization:
Schizophrenia
NMDA receptor
D-serine
 Recent onset
Negative symptoms
Cognition

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Adjuvants, Immunologic
 Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on June 18, 2013