SchizophreniaPhase 2SATROSNCT01459029
High Dose D-Serine as Adjuvant Treatment for Recent Onset Schizophrenia
A Phase 2 study testing D-serine in people with Schizophrenia, run by Hadassah Medical Organization at 2 sites in Israel.
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. Read more about this study
- Who is it for?
- Ages 18 to 30 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- D-serine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 54 participants
- Where
- 2 sitesIsrael
- Study dates
- Nov 2011to Oct 2014
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 30 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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)
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
Israel2 sites
Ezrath Nashim - Herzog Memorial Hospital & Community Clinics
Jerusalem
Uriel Heresco-Levy, MD, 00 972 2 5316906, heresco@md.huji.ac.il
Uriel Heresco-Levy, MD
Hadassah Medical Organization
Jerusalem
Arik Tzukert, DMD, 00 972 2 6776095, arik@hadassah.org.il
Hadas Lemberg, PhD, 00 972 2 6777572, lhadas@hadassah.org.il
About this study
Official title: High Dose D-Serine as Adjuvant Treatment for Recent Onset Schizophrenia : A Randomized, Double-Blind, Placebo-Controlled Study
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.
Read the 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.
- Conditions
- Schizophrenia
- Being tested
- D-serine
- Keywords
- Schizophrenia, NMDA receptor, D-serine, Recent onset, Negative symptoms, Cognition
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
D-serineDrug
Adjuvant treatment with D-serine up to 6000 mg/day vs. placebo
| Study group | Role | What they receive |
|---|---|---|
| D-serine | Active comparator | D-serine up to 6000 mg/day subject to tolerability Receives: Drug: D-serine |
| Control | Placebo comparator | Treatment with inert capsules (placebo) Receives: Drug: D-serine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from Baseline in the Total Score of the Positive and Negative Syndrome Scale (PANSS)
Measured: Biweekly for 12 weeks
Secondary outcomes (11)
Change from Baseline in the Composite T-score of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Battery
Measured: 12 weeks
Change from Baseline in the Subscales of PANSS
Measured: Biweekly for 12 weeks
Change from Baseline in the Clinical Global Impressions (CGI)
Measured: Biweekly for 12 weeks
Change from Baseline in the Scale for the Assessment of Negative Symptoms (SANS)
Measured: Biweekly for 12 weeks
Change from Baseline in the Calgary Depression Scale for Schizophrenia (CDSS
Measured: Biweekly for 12 weeks
Change from Baseline in the Quality of Life Scale (QOL)
Measured: Biweekly for 12 weeks
Change from Baseline in the Simpson-Angus Extrapyramidal Rating Scale (SAS)
Measured: Biweekly for 12 weeks
Change from Baseline in the Abnormal Involuntary Movement Scale (AIMS)
Measured: Biweekly for 12 weeks
Change from Baseline in the Udvalg for Kliniske Undersgelser (UKU) Side Effect Rating Scale
Measured: Biweekly for 12 weeks
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
Measured: 12 weeks
Amino Acid Serum Levels
Glutamate, Glycine, D-serine
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2011 (estimated)
- Study startNov 2011
- Primary completionOct 2013 (estimated)
- Study completionOct 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by Hadassah Medical OrganizationThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 54 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hadassah Medical Organization
- Sponsor type
- University, hospital or other
- Collaborators
- Herzog Hospital
- Responsible party
- Sponsor
- Investigators
- Amit Lotan, MD, Principal investigator, Hadassah Medical OrganizationBernard Lerer, MD, Study director, Hadassah Medical OrganizationUriel Heresco-Levy, MD, Study director, Ezrath Nashim - Herzog Memorial Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01459029
- Sponsor's protocol ID
- 043211- HMO-CTIL
- Acronym
- SATROS
- Status last verified
- Oct 2011
- First submitted
- 9 Oct 2011
- Last updated
- 25 Oct 2011
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Oct 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- High Dose D-Serine as Adjuvant Treatment for Recent Onset Schizophrenia : A Randomized, Double-Blind, Placebo-Controlled Study
- ClinicalTrials.gov ID
- NCT01459029
- Acronym / sponsor ID
- SATROS / 043211- HMO-CTIL
- Conditions
- Schizophrenia
- Keywords
- Schizophrenia, NMDA receptor, D-serine, Recent onset, Negative symptoms, Cognition
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 54 participants (estimated)
- Lead sponsor
- Hadassah Medical OrganizationUniversity, hospital or other
- Collaborators
- Herzog Hospital
- Study start
- Nov 2011
- Primary completion
- Oct 2013 (estimated)
- Study completion
- Oct 2014 (estimated)
- First posted
- 25 Oct 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| D-serine | Active comparator | Drug: D-serineD-serine up to 6000 mg/day subject to tolerability |
| Control | Placebo comparator | Drug: D-serineTreatment with inert capsules (placebo) |
Who may qualify
- Ages
- 18 to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| D-serineAdjuvant treatment with D-serine up to 6000 mg/day vs. placebo | Drug | Control, D-serine |
Primary outcome
Change from Baseline in the Total Score of the Positive and Negative Syndrome Scale (PANSS)
Time frame: Biweekly for 12 weeks
11 secondary outcomes
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
Change from Baseline in the Subscales of PANSS
Time frame: Biweekly for 12 weeks
Change from Baseline in the Clinical Global Impressions (CGI)
Time frame: Biweekly for 12 weeks
Change from Baseline in the Scale for the Assessment of Negative Symptoms (SANS)
Time frame: Biweekly for 12 weeks
Change from Baseline in the Calgary Depression Scale for Schizophrenia (CDSS
Time frame: Biweekly for 12 weeks
Change from Baseline in the Quality of Life Scale (QOL)
Time frame: Biweekly for 12 weeks
Change from Baseline in the Simpson-Angus Extrapyramidal Rating Scale (SAS)
Time frame: Biweekly for 12 weeks
Change from Baseline in the Abnormal Involuntary Movement Scale (AIMS)
Time frame: Biweekly for 12 weeks
Change from Baseline in the Udvalg for Kliniske Undersgelser (UKU) Side Effect Rating Scale
Time frame: Biweekly for 12 weeks
Change from Baseline in the Prepulse Inhibition (PPI) of Startle
Time frame: 12 weeks
Amino Acid Serum Levels
Time frame: 12 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Oct 2011.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amit Lotan, MD principal investigator
Hadassah Medical Organization
Bernard Lerer, MD study director
Hadassah Medical Organization
Uriel Heresco-Levy, MD study director
Ezrath Nashim - Herzog Memorial Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing D-serine in people with Schizophrenia, run by Hadassah Medical Organization at 2 sites in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 25 Oct 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Amit Lotan, MD (00 972 2 6777184, amitlo@hadassah.org.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from Baseline in the Total Score of the Positive and Negative Syndrome Scale (PANSS) (time frame: Biweekly for 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Oct 2011.