SchizophreniaPhase 2NCT00322023
Safety and Effectiveness of D-serine in Schizophrenia
A Phase 2 study testing D-serine in people with Schizophrenia, run by Nathan Kline Institute for Psychiatric Research at 3 sites in United States.
Trial summary
This study will determine whether increasing D-serine within the body will improve negative symptoms and cognitive impairments in people with schizophrenia. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- D-serine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 3 sitesUnited States
- Study dates
- Mar 2006to Jan 2009
- 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 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Structured Clinical Interview for DSM-III-R diagnosis of schizophrenia or schizoaffective disorder
- PANSS 3 factor negative symptom inclusion score greater than 20 prior to study entry
- PANSS total score between 60 and 110
- Simpson-Angus Scale total score of 12 or less
- Calgary Depression Inventory total score of 10 and suicide score less than 2
- No change in Clinical Global Impressions (CGI) Scale score prior to study entry
- Chlorpromazine (CPZ) equivalent of 1500 or less
- Willing to use an effective form of birth control throughout the study if sexually active
Who cannot join
- High extrapyramidal symptom (EPS) levels
- Began, discontinued, or adjusted psychotropic medication within 2 weeks of study entry
- Taking investigational medication within 2 weeks of study entry
- Contraindication to study medication
- Serious or unstable medical illness
- Pregnant or breastfeeding
Show all 12Show fewer
- Alcohol or drug abuse within 6 months of study entry
- Diagnosed with neurodegenerative disease or a seizure disorder
- History of a kidney impairment
- Currently taking clozapine
- Currently taking more than two antipsychotic medications
- Currently taking stimulants or cholinesterase inhibitors
Trial locations and contacts
3 sites in 1 country.
United States3 sites
The Zucker Hillside Hospital
Glen Oaks, New York, 11004
Yale University School of Medicine
New Haven, Connecticut, 06512
The Nathan S. Kline Institute for Psychiatric Research
Orangeburg, New York, 10962
About this study
Official title: PK/PD Study of Escalating Dose D-serine as Adjunctive Treatment in Schizophrenia
This study will determine whether increasing D-serine within the body will improve negative symptoms and cognitive impairments in people with schizophrenia.
Read the detailed description
Schizophrenia is a life-long brain disorder affecting approximately 1 percent of Americans each year. Schizophrenia can be extremely disabling, causing people to hear voices, experience paranoia or hallucinations, believe that others are controlling their thoughts, and even fail at maintaining a job or caring for themselves. Current medications help to relieve most of these symptoms, but not all. Some people with schizophrenia still suffer from negative symptoms, such as difficulty with talking, expressing emotions, and motivation; they may also suffer from cognitive impairments, such as decreased concentration and memory loss. D-serine, an amino acid found within the body, activates brain cell receptors that appear to play a role in learning and memory. This study will determine whether adding a D-serine solution to a stable antipsychotic medication regimen will decrease negative symptoms in people with schizophrenia.
Participants in this open-label study will remain on their regular medication regimen for at least 2 weeks. During this time and before starting treatment, participants will be interviewed about their emotional problems, marital status, education, family background, employment history, and any drug or alcohol problems. Participants will also undergo a physical exam, an electrocardiogram (EKG), vital sign measurements, psychological tests, cognitive tasks, and an electroencephalogram (EEG). Participants will then begin 4 weeks of treatment with D-serine. In addition to participants' regular medication regimen, they will drink a D-serine powder mixed with water twice daily. Every 2 weeks, participants will undergo a physical exam and an interview about any changes in symptoms or emotional problems that they may be experiencing. Blood and urine samples will be taken throughout the study. After 4 weeks, participants will undergo an EKG, EEG, and the same psychological tests and cognitive tasks completed prior to treatment. A follow-up visit will occur 2 weeks post-treatment to monitor any changes in negative symptoms.
- Conditions
- Schizophrenia
- Being tested
- D-serine
- Keywords
- Negative symptoms, NMDA, Glutamate, Glycine
- 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
D-serine at following dose levels: 30 mg/kg, 60 mg/kg, and 120 mg/kg. PK/PD studies done at day 1. Medication will be administered as powder dissolved in liquid given in two divided doses daily for 4 weeks.
D-serineDrug
D-serineDrug
D-serineDrug
| Study group | Role | What they receive |
|---|---|---|
| D-serine 30 mg/kg | Experimental | D-serine 30 mg/kg Receives: Drug: D-serine |
| D-serine 60 mg/kg | Experimental | D-serine 60 mg/kg Receives: Drug: D-serine |
| D-serine 120 mg/kg | Experimental | D-serine 120 mg/kg Receives: Drug: D-serine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Renal Safety Measures
number of renal adverse events (serum and urinalysis)
Measured: Measured at Week 4
Secondary outcomes (2)
Positive and Negative Symptoms Scale (PANSS)
Absolute Change in PANSS over four weeks (change between baseline and final measurements). The PANSS is a 30-item rating scale widely used in assessment of medication effects in schizophrenia. The PANSS ranges from 30-210, with lower scores showing less symptoms. Larger change is better.
Measured: Measured at Week 4
Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Battery
Change over 4 weeks. The MATRICS is a scale measuring cognition, and reported as T-score, with 50 as the population average and every 10 points representing a change of 1 standard deviation from the population average. Higher scores represent an improvement
Measured: Measured at Week 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2006 (estimated)
- Study startMar 2006
- Primary completionJan 2009
- Study completionJan 2009
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 SchizophreniaStudies 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nathan Kline Institute for Psychiatric Research
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Daniel C. Javitt, MD, PhD, National Institute of Mental Health (NIMH)
- Investigators
- Daniel C. Javitt, MD, PhD, Principal investigator, Nathan Kline Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00322023
- Sponsor's protocol ID
- U01MH074356
- Other IDs
- U01MH074356, DATR A5-EPTD
- Status last verified
- Sep 2020
- First submitted
- 2 May 2006
- Last updated
- 5 Oct 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Kantrowitz JT, Epstein ML, Lee M, Lehrfeld N, Nolan KA, Shope C, Petkova E, Silipo G, Javitt DC. Improvement in mismatch negativity generation during d-serine treatment in schizophrenia: Correlation with symptoms. Schizophr Res. 2018 Jan;191:70-79. doi: 10.1016/j.schres.2017.02.027. Epub 2017 Mar 18.
PubMed 28318835
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PK/PD Study of Escalating Dose D-serine as Adjunctive Treatment in Schizophrenia
- ClinicalTrials.gov ID
- NCT00322023
- Acronym / sponsor ID
- U01MH074356
- Conditions
- Schizophrenia
- Keywords
- Negative symptoms, NMDA, Glutamate, Glycine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- Nathan Kline Institute for Psychiatric ResearchUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Mar 2006
- Primary completion
- Jan 2009 (actual)
- Study completion
- Jan 2009 (actual)
- First posted
- 4 May 2006 (estimated)
- Results
- Posted 5 Oct 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will determine whether increasing D-serine within the body will improve negative symptoms and cognitive impairments in people with schizophrenia.
Detailed description
Schizophrenia is a life-long brain disorder affecting approximately 1 percent of Americans each year. Schizophrenia can be extremely disabling, causing people to hear voices, experience paranoia or hallucinations, believe that others are controlling their thoughts, and even fail at maintaining a job or caring for themselves. Current medications help to relieve most of these symptoms, but not all. Some people with schizophrenia still suffer from negative symptoms, such as difficulty with talking, expressing emotions, and motivation; they may also suffer from cognitive impairments, such as decreased concentration and memory loss. D-serine, an amino acid found within the body, activates brain cell receptors that appear to play a role in learning and memory. This study will determine whether adding a D-serine solution to a stable antipsychotic medication regimen will decrease negative symptoms in people with schizophrenia.
Participants in this open-label study will remain on their regular medication regimen for at least 2 weeks. During this time and before starting treatment, participants will be interviewed about their emotional problems, marital status, education, family background, employment history, and any drug or alcohol problems. Participants will also undergo a physical exam, an electrocardiogram (EKG), vital sign measurements, psychological tests, cognitive tasks, and an electroencephalogram (EEG). Participants will then begin 4 weeks of treatment with D-serine. In addition to participants' regular medication regimen, they will drink a D-serine powder mixed with water twice daily. Every 2 weeks, participants will undergo a physical exam and an interview about any changes in symptoms or emotional problems that they may be experiencing. Blood and urine samples will be taken throughout the study. After 4 weeks, participants will undergo an EKG, EEG, and the same psychological tests and cognitive tasks completed prior to treatment. A follow-up visit will occur 2 weeks post-treatment to monitor any changes in negative symptoms.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| D-serine 30 mg/kg | Experimental | Drug: D-serineD-serine 30 mg/kg |
| D-serine 60 mg/kg | Experimental | Drug: D-serineD-serine 60 mg/kg |
| D-serine 120 mg/kg | Experimental | Drug: D-serineD-serine 120 mg/kg |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Structured Clinical Interview for DSM-III-R diagnosis of schizophrenia or schizoaffective disorder
- PANSS 3 factor negative symptom inclusion score greater than 20 prior to study entry
- PANSS total score between 60 and 110
- Simpson-Angus Scale total score of 12 or less
- Calgary Depression Inventory total score of 10 and suicide score less than 2
Key exclusion criteria (12 listed)
- High extrapyramidal symptom (EPS) levels
- Began, discontinued, or adjusted psychotropic medication within 2 weeks of study entry
- Taking investigational medication within 2 weeks of study entry
- Contraindication to study medication
- Serious or unstable medical illness
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-serineD-serine at following dose levels: 30 mg/kg, 60 mg/kg, and 120 mg/kg. PK/PD studies done at day 1. Medication will be administered as powder dissolved in liquid given in two divided doses daily for 4 weeks. | Drug | D-serine 120 mg/kg, D-serine 30 mg/kg, D-serine 60 mg/kg |
| D-serine | Drug | D-serine 30 mg/kg |
| D-serine | Drug | D-serine 60 mg/kg |
| D-serine | Drug | D-serine 120 mg/kg |
Primary outcome
Renal Safety Measures
Time frame: Measured at Week 4
number of renal adverse events (serum and urinalysis)
2 secondary outcomes
Positive and Negative Symptoms Scale (PANSS)
Time frame: Measured at Week 4
Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Battery
Time frame: Measured at Week 4
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28318835Kantrowitz JT, Epstein ML, Lee M, Lehrfeld N, Nolan KA, Shope C, Petkova E, Silipo G, Javitt DC. Improvement in mismatch negativity generation during d-serine treatment in schizophrenia: Correlation with symptoms. Schizophr Res. 2018 Jan;191:70-79. doi: 10.1016/j.schres.2017.02.027. Epub 2017 Mar 18.
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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
3 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 Nathan Kline Institute for Psychiatric Research at 3 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 8 inclusion and 12 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 5 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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. 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 5 Oct 2020). 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?
Renal Safety Measures (time frame: Measured at Week 4). 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 NCT00322023, 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 5 Oct 2020.