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| ID | Type | Description | Link |
|---|---|---|---|
| U01MH074356 | U.S. NIH Grant/Contract | View source | |
| DATR A5-EPTD |
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| Name | Class |
|---|---|
| National Institute of Mental Health (NIMH) | NIH |
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This study will determine whether increasing D-serine within the body will improve negative symptoms and cognitive impairments in people with schizophrenia.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| D-serine 30 mg/kg | Experimental | D-serine 30 mg/kg |
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| D-serine 60 mg/kg | Experimental | D-serine 60 mg/kg |
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| D-serine 120 mg/kg | Experimental | D-serine 120 mg/kg |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| D-serine | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Renal Safety Measures | number of renal adverse events (serum and urinalysis) | Measured at Week 4 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 at Week 4 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Daniel C. Javitt, MD, PhD | Nathan Kline Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Yale University School of Medicine | New Haven | Connecticut | 06512 | United States | ||
| The Zucker Hillside Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28318835 | Derived | 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. |
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Nathan Kline Institute, Yale University, Zucker Hillside
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| ID | Title | Description |
|---|---|---|
| FG000 | D-serine 30 mg/kg | Open label, adjunctive to antipsychotics for 4 weeks |
| FG001 | D-serine 60 mg/kg | Open label, adjunctive to antipsychotics for 4 weeks |
| FG002 | D Serine 120 mg/kg | Open label, adjunctive to antipsychotics for 4 weeks |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | D-serine 30 mg/kg | |
| BG001 | D-serine 60 mg/kg | |
| BG002 | D Serine 120 mg/kg |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Renal Safety Measures | number of renal adverse events (serum and urinalysis) | study completers | Posted | Number | adverse events | Measured at Week 4 |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | D-serine 30 mg/kg | 4 weeks of adjunctive treatment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Proteinuria | Renal and urinary disorders | Systematic Assessment | 2+ proteinuria without glycosuria during the final week of treatment with no significant change in creatinine that resolved following dserine discontinuation. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| asymptomatic transaminitis | Hepatobiliary disorders | Systematic Assessment |
Open Label
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Daniel Javitt | Nathan Kline Institute | 845-398-6534 | javitt@nki.rfmh.org |
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| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
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| D-serine | Drug |
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| D-serine | Drug |
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| D-serine | Drug |
|
| 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 at Week 4 |
| Glen Oaks |
| New York |
| 11004 |
| United States |
| The Nathan S. Kline Institute for Psychiatric Research | Orangeburg | New York | 10962 | United States |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
|
|
| Secondary | 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. | Study completers | Posted | Mean | Standard Deviation | units on a scale | Measured at Week 4 |
|
|
|
|
| Secondary | 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 | study completers | Posted | Mean | Standard Deviation | units on a scale | Measured at Week 4 |
|
|
|
|
| 0 |
| 12 |
| 0 |
| 12 |
| EG001 | D-serine 60 mg/kg | 4 weeks of adjunctive treatment | 0 | 19 | 0 | 19 |
| EG002 | D Serine 120 mg/kg | 4 weeks of adjunctive treatment | 1 | 16 | 2 | 16 |
|
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These are paired t test baseline vs final for the 60 mg/kg dose
| <0.05 |
| Superiority |
| t-test, 2 sided | <0.01 | Superiority | These are paired t test baseline vs final for the 120 mg/kg dose |
These are paired t test baseline vs final for 60mg/kg |
| Superiority |
| t-test, 2 sided | 0.01 | These are paired t test baseline vs final for 120mg/kg | Superiority |