Schizophrenia ProdromePhase 2NCT00826202
D-serine for the Schizophrenia Prodrome
A Phase 2 study testing D-serine in people with Schizophrenia Prodrome, run by Nathan Kline Institute for Psychiatric Research at 4 sites in United States.
Trial summary
The purpose of the study is to determine the safety and efficacy of D-serine as an early intervention treatment for the schizophrenia prodrome condition. This study is a placebo-controlled trial of D-serine in the symptomatic treatment of patients with the schizophrenia prodrome. Read more about this study
- Who is it for?
- Ages 13 to 35 years
- Conditions the study is for
- Schizophrenia Prodrome
- What is being tested?
- D-serine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- 4 sitesUnited States
- Study dates
- Mar 2009to Nov 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 13 to 35 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- treatment seeking subjects ages 13-35 who meet criteria for the schizophrenia prodrome (see criteria below) and who are able to give written informed assent or consent.
- Subjects must score at least 20 on the Scale of Prodromal Symptoms (SOPS) total score at visit -1.
- Patients may be receiving ongoing treatment with antipsychotic, antidepressant or anti-anxiety medications as prescribed by their treating physician, or may be medication free.
- Patients may enroll in the treatment phase only if they have been on fixed medication dosage for at least 4 weeks. If possible, medication will be held constant during course of study. Subjects will not be excluded or dropped from the study if they have a psychiatric diagnosis or must start a new medication unless the diagnosis is "psychosis". Medication changes and increases or decreases in medication will be permitted at the discretion of the treating physician, and, if they occur, will be treated as secondary outcome measures.
Who cannot join
- inability to give informed assent or consent,
- history of psychosis (e.g. frank delusions, hallucinations, or thought disorder),
- psychotropic medication begun or dose adjusted within 4 weeks of visit 0,
- contraindication to study medication,
- inclusion symptoms better accounted for by comorbid diagnosis,
- treatment need for comorbid diagnosis outweighs that for prodromal symptoms,
Show all 20Show fewer
- unstable medical illness,
- females who are of childbearing potential but are not taking adequate contraceptive precautions or who are pregnant or breast feeding,
- alcohol or drug abuse or dependence in the past three months,
- either of the following: Subjects with significant renal disease or estimated GFR below 60 (MDRD, http://www.kidney.org/professionals/kdoqi/gfr_calculator.cfm) will be excluded (see below for details). Any subject taking or unwilling to avoid other nephrotoxic agents during the course of the study (NSAIDS, ACE inhibitors, ARB's, calcineurin inhibitors, or aminoglycosides) will also be excluded. Therefore, patients will be asked during the study to take acetaminophen (e.g. if they have a headache) and to avoid taking ibuprofen.
- For adolescents (ages 13-17), more stringent renal exclusion criteria will be adhered to:
- estimated GFR is < 89 cc/min/1.73 m2 as calculated by the Schwartz formula (http://www.kidney.org/professionals/kdoqi/gfr_calculatorPed.cfm),
- difference of ≥0.3mg/dl between the two baseline serum creatinine values,
- baseline proteinuria defined by a spot urine protein:creatinine of 0.2 or greater, or
- baseline glucosuria (the presence of glucosuria).
- Schizophrenia Prodrome Criteria:
- We will be enrolling both Attenuated Positive Syndrome (APS) [1], Genetic Familial Risk (GFR) [1] and Clinically High Risk Negative (CHR-) symptom prodromes to this study. A separate analysis will be done for the APS and CHR- patients.
- Attenuated Positive Syndrome: One or more of the 5 SOPS positive items scoring in the prodromal range (rating of 3-5) AND Symptoms beginning within the past year or increasing 1 or more points within the past year AND Symptoms occurring at least once per wk for last month.
- Genetic Familial Risk: First degree relative with history of any psychotic disorder OR Criteria for schizotypal personality disorder met in patient AND GAF drop of at least 30% over the last month vs 1 year ago. In our experience, very few patients only meet criteria for this syndrome.
- CHR-: To make criteria, social isolation must be present along with either flat affect or impairment in the occupational role. Therefore to meet criteria for CHR-, Social Anhedonia (N1) has to be present at a score of 3 or above, and, in addition, one of the other two symptoms (N3 or N6) listed must also present at a minimum level of 3. Note: a score of "6" on these items is not considered exclusionary.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Zucker Hillside Hospital
Glen Oaks, New York
Yale University
New Haven, Connecticut
New York State Psychiatric Institute
New York, New York, 10032
Nathan Kline Institute
Orangeburg, New York, 10962
About this study
Official title: D-Serine vs Placebo for the Schizophrenia Prodrome
The purpose of the study is to determine the safety and efficacy of D-serine as an early intervention treatment for the schizophrenia prodrome condition. This study is a placebo-controlled trial of D-serine in the symptomatic treatment of patients with the schizophrenia prodrome. Seventy two subjects meeting criteria for the schizophrenia prodrome will be included in this study, 24 at each site (Yale, Nathan Kline Institute and Zucker Hillside Hospital). The primary outcome measures will include symptom and neuropsychological measures. The duration of this study is two and a half years.
This research with D-serine holds out the prospect of direct benefit for the patient's current symptoms. Subjects may also benefit from the close monitoring of their symptoms, so that, if schizophrenic psychosis does occur, the psychosis will be recognized and treatment may begin with minimal delay. This study also could be of benefit by suggesting a promising lead in early intervention in the schizophrenic prodrome.
Overall Design Summary. We propose for prodromal patients to be randomized to D-serine vs placebo for 16 weeks. To insure that all subjects have the opportunity to receive D-serine, there will be an optional 16 week cross-over trial on the alternate study medication. No subject will be on D-serine for longer than 16 weeks. Admission criteria, Assessment Procedures, and Study Design will be the same across all sites. The procedures and timeline are shown in Table 1. The procedures and timeline are the same for the initial randomized 16 week trial and the optional cross-over trial on the alternate study medication. If patient's opt for the 16 week treatment on the alternate medication, we will use their assessments from end of initial treatment as baseline for 16 week treatment on alternate medication. Subjects will be seen for two preliminary visits, then once in treatment, subjects will be seen weekly for the first 5 visits then biweekly thereafter. A safety blood and urine collection will be done on day 3 (3 days after the start of study medication). Vital signs and weight, blood draw and urine collection for safety measures, urine pregnancy test and urine for toxicology will be repeated throughout treatment. Adverse effects ratings and symptom assessments will be repeated at each visit. Neuropsychological assessment and optional "Biomarker study" visual, auditory and ERPs tasks will be administered during one of the two preliminary visits then again at study endpoint. Any patients who convert to frank psychosis will be referred/offered immediate treatment.
- Conditions
- Schizophrenia Prodrome
- Being tested
- D-serine, Placebo
- Keywords
- schizophrenia, d-serine, prodrome
- 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
60 mg/kg/day
PlaceboOther
Inert Placebo
| Study group | Role | What they receive |
|---|---|---|
| D serine | Experimental | 60 mg/kg/day Receives: Drug: D-serine |
| Placebo | Placebo comparator | Not described Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Scale of Prodromal Symptoms (SOPS) Negative Scale
The SOPS Negative symptom scale consists of six Negative Symptom items. Each item has a severity scale rating from 0 (Never, Absent) to 6 (Severe/Extreme). The severity of the prodromal state is judged according to the sum of the ratings from each of the SOPS items and ranges from 0 to 36.
Measured: 16 weeks
Secondary outcomes (3)
Scale of Prodromal Symptoms (SOPS) Total
The SOPS Total consists of five Positive Symptom items, six Negative Symptom items, four Disorganization Symptom items, and four General Symptom items. Each item has a severity scale rating from 0 (Never, Absent) to 6 (Severe/Extreme-and Psychotic, for the positive items). The severity of the prodromal state is judged according to the sum of the ratings from each of the SOPS items and ranges from 0 to 114.
Measured: 16 weeks
IL6 Levels
Final IL6 levels (pg/ml) in available subjects
Measured: 16 weeks
Pittsburgh Sleep Quality Index Score
The Pittsburgh Sleep Quality Index (PSQI) consists of 19 self-rated questions and five questions rated by the bed partner or roommate. The latter five questions are used for clinical information only, are not tabulated in the scoring of the PSQI. The 19 self-rated questions assess a wide variety of factors relating to sleep quality, including estimates of sleep duration and latency and of the frequency and severity of specific sleep-related problems. These I9 items are grouped into seven component scores, each weighted equally on a 0-3 scale. The seven component scores are then summed to yield a global PSQI score, which has a range of 0-21; higher scores
Measured: 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2009 (estimated)
- Study startMar 2009
- Primary completionNov 2012
- Study completionNov 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Schizophrenia ProdromeStudies of the same condition, open and under way.
- 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
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nathan Kline Institute for Psychiatric Research
- Sponsor type
- University, hospital or other
- Collaborators
- Yale University, The Zucker Hillside Hospital, National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- Daniel C Javitt, MD, PhD, Principal investigator, Nathan Kline Institute for Psychiatric Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00826202
- Sponsor's protocol ID
- 08I/C33
- Other IDs
- CDDG 1 U01 MH074356-01
- Status last verified
- Jul 2017
- First submitted
- 21 Jan 2009
- Last updated
- 14 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Kantrowitz JT, Woods SW, Petkova E, Cornblatt B, Corcoran CM, Chen H, Silipo G, Javitt DC. D-serine for the treatment of negative symptoms in individuals at clinical high risk of schizophrenia: a pilot, double-blind, placebo-controlled, randomised parallel group mechanistic proof-of-concept trial. Lancet Psychiatry. 2015 May;2(5):403-412. doi: 10.1016/S2215-0366(15)00098-X. Epub 2015 Apr 28.
PubMed 26360284
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- D-Serine vs Placebo for the Schizophrenia Prodrome
- ClinicalTrials.gov ID
- NCT00826202
- Acronym / sponsor ID
- 08I/C33
- Conditions
- Schizophrenia Prodrome
- Keywords
- schizophrenia, d-serine, prodrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- Nathan Kline Institute for Psychiatric ResearchUniversity, hospital or other
- Collaborators
- Yale University, The Zucker Hillside Hospital, National Institute of Mental Health (NIMH)
- Study start
- Mar 2009
- Primary completion
- Nov 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 22 Jan 2009 (estimated)
- Results
- Posted 8 Feb 2017
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 the study is to determine the safety and efficacy of D-serine as an early intervention treatment for the schizophrenia prodrome condition. This study is a placebo-controlled trial of D-serine in the symptomatic treatment of patients with the schizophrenia prodrome. Seventy two subjects meeting criteria for the schizophrenia prodrome will be included in this study, 24 at each site (Yale, Nathan Kline Institute and Zucker Hillside Hospital). The primary outcome measures will include symptom and neuropsychological measures. The duration of this study is two and a half years.
This research with D-serine holds out the prospect of direct benefit for the patient's current symptoms. Subjects may also benefit from the close monitoring of their symptoms, so that, if schizophrenic psychosis does occur, the psychosis will be recognized and treatment may begin with minimal delay. This study also could be of benefit by suggesting a promising lead in early intervention in the schizophrenic prodrome.
Overall Design Summary. We propose for prodromal patients to be randomized to D-serine vs placebo for 16 weeks. To insure that all subjects have the opportunity to receive D-serine, there will be an optional 16 week cross-over trial on the alternate study medication. No subject will be on D-serine for longer than 16 weeks. Admission criteria, Assessment Procedures, and Study Design will be the same across all sites. The procedures and timeline are shown in Table 1. The procedures and timeline are the same for the initial randomized 16 week trial and the optional cross-over trial on the alternate study medication. If patient's opt for the 16 week treatment on the alternate medication, we will use their assessments from end of initial treatment as baseline for 16 week treatment on alternate medication. Subjects will be seen for two preliminary visits, then once in treatment, subjects will be seen weekly for the first 5 visits then biweekly thereafter. A safety blood and urine collection will be done on day 3 (3 days after the start of study medication). Vital signs and weight, blood draw and urine collection for safety measures, urine pregnancy test and urine for toxicology will be repeated throughout treatment. Adverse effects ratings and symptom assessments will be repeated at each visit. Neuropsychological assessment and optional "Biomarker study" visual, auditory and ERPs tasks will be administered during one of the two preliminary visits then again at study endpoint. Any patients who convert to frank psychosis will be referred/offered immediate treatment.
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 | Experimental | Drug: D-serine60 mg/kg/day |
| Placebo | Placebo comparator | Other: Placebo |
Who may qualify
- Ages
- 13 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- treatment seeking subjects ages 13-35 who meet criteria for the schizophrenia prodrome (see criteria below) and who are able to give written informed assent or consent.
- Subjects must score at least 20 on the Scale of Prodromal Symptoms (SOPS) total score at visit -1.
- Patients may be receiving ongoing treatment with antipsychotic, antidepressant or anti-anxiety medications as prescribed by their treating physician, or may be medication free.
- Patients may enroll in the treatment phase only if they have been on fixed medication dosage for at least 4 weeks. If possible, medication will be held constant during course of study. Subjects will not be excluded or dropped from the study if they have a psychiatric diagnosis or must start a new medication unless the diagnosis is "psychosis". Medication changes and increases or decreases in medication will be permitted at the discretion of the treating physician, and, if they occur, will be treated as secondary outcome measures.
Key exclusion criteria (20 listed)
- inability to give informed assent or consent,
- history of psychosis (e.g. frank delusions, hallucinations, or thought disorder),
- psychotropic medication begun or dose adjusted within 4 weeks of visit 0,
- contraindication to study medication,
- inclusion symptoms better accounted for by comorbid diagnosis,
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-serine60 mg/kg/day | Drug | D serine |
| PlaceboInert Placebo | Other | Placebo |
Primary outcome
Scale of Prodromal Symptoms (SOPS) Negative Scale
Time frame: 16 weeks
The SOPS Negative symptom scale consists of six Negative Symptom items. Each item has a severity scale rating from 0 (Never, Absent) to 6 (Severe/Extreme). The severity of the prodromal state is judged according to the sum of the ratings from each of the SOPS items and ranges from 0 to 36.
3 secondary outcomes
Scale of Prodromal Symptoms (SOPS) Total
Time frame: 16 weeks
IL6 Levels
Time frame: 16 weeks
Pittsburgh Sleep Quality Index Score
Time frame: 16 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 26360284Kantrowitz JT, Woods SW, Petkova E, Cornblatt B, Corcoran CM, Chen H, Silipo G, Javitt DC. D-serine for the treatment of negative symptoms in individuals at clinical high risk of schizophrenia: a pilot, double-blind, placebo-controlled, randomised parallel group mechanistic proof-of-concept trial. Lancet Psychiatry. 2015 May;2(5):403-412. doi: 10.1016/S2215-0366(15)00098-X. Epub 2015 Apr 28.
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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.
Daniel C Javitt, MD, PhD principal investigator
Nathan Kline Institute for Psychiatric Research
4 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 Prodrome, run by Nathan Kline Institute for Psychiatric Research at 4 sites in United States.
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 4 inclusion and 20 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: finished, as of the sponsor's last update on 14 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. 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?
Yes. Results are posted in the registry (first posted 8 Feb 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Scale of Prodromal Symptoms (SOPS) Negative Scale (time frame: 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00826202, which also lists 1 linked publication.
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 14 Aug 2017.