NCT00826202

Brief 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. 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
44

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Mar 2009

Typical duration for phase_2

Geographic Reach
1 country

4 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 21, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

January 22, 2009

Completed
1 month until next milestone

Study Start

First participant enrolled

March 1, 2009

Completed
3.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2012

Completed
4.3 years until next milestone

Results Posted

Study results publicly available

February 8, 2017

Completed
Last Updated

August 14, 2017

Status Verified

July 1, 2017

Enrollment Period

3.7 years

First QC Date

January 21, 2009

Results QC Date

April 15, 2015

Last Update Submit

July 7, 2017

Conditions

Schizophrenia Prodrome

Keywords

schizophreniad-serineprodrome

Outcome Measures

Primary Outcomes (1)

  • 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.

    16 weeks

Secondary Outcomes (3)

  • Scale of Prodromal Symptoms (SOPS) Total

    16 weeks

  • IL6 Levels

    16 weeks

  • Pittsburgh Sleep Quality Index Score

    16 weeks

Study Arms (2)

D serine

EXPERIMENTAL

60 mg/kg/day

Drug: D-serine

Placebo

PLACEBO COMPARATOR
Other: Placebo

Interventions

D-serineDRUG

60 mg/kg/day

D serine
PlaceboOTHER

Inert Placebo

Placebo

Eligibility Criteria

Age13 Years - 35 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • 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.

You may not qualify if:

  • 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,
  • treatment need for comorbid diagnosis outweighs that for prodromal symptoms,
  • 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.
  • 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.
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Yale University

New Haven, Connecticut, United States

Location

Zucker Hillside Hospital

Glen Oaks, New York, United States

Location

New York State Psychiatric Institute

New York, New York, 10032, United States

Location

Nathan Kline Institute

Orangeburg, New York, 10962, United States

Location

Related Publications (1)

  • 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.

    PMID: 26360284RESULT

MeSH Terms

Conditions

Schizophrenia

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic DisordersMental Disorders

Results Point of Contact

Title
Daniel Javitt MD, PhD
Organization
Nathan Kline Institute
javitt@nki.rfmh.org
845-398-6534

Study Officials

  • Daniel C Javitt, MD, PhD

    Nathan Kline Institute for Psychiatric Research

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 21, 2009

First Posted

January 22, 2009

Study Start

March 1, 2009

Primary Completion

November 1, 2012

Study Completion

November 1, 2012

Last Updated

August 14, 2017

Results First Posted

February 8, 2017

Record last verified: 2017-07

Locations

US(4)