SchizophreniaPhase 3NCT00237809
D-Serine Treatment of Negative Symptoms and Cognitive Deficits in Schizophrenia
A Phase 3 study testing D-serine and Cognitive Retraining (CRT) in people with Schizophrenia and Schizoaffective Disorder, run by Yale University at 2 sites in United States.
Trial summary
This study is based on the hypothesis that by increasing N-methyl-D-aspartic acid (NMDA) receptor function in the brain and thereby increasing the capacity of the brain to both form new connections and strengthen existing connections, schizophrenic patients may derive both greater and sustained benefit from cognitive… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Schizophrenia, Schizoaffective Disorder
- What is being tested?
- D-serine and Cognitive Retraining (CRT)
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 104 participants
- Where
- 2 sitesUnited States
- Study dates
- Sep 2002to Sep 2012
- Phase
- Phase 3
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of schizophrenia or schizoaffective disorder
Who cannot join
- Pregnant or lactating
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Connecticut Mental Health Center
New Haven, Connecticut, 06508
VA Connecticut Healthcare System
West Haven, Connecticut, 06516
About this study
This study is based on the hypothesis that by increasing N-methyl-D-aspartic acid (NMDA) receptor function in the brain and thereby increasing the capacity of the brain to both form new connections and strengthen existing connections, schizophrenic patients may derive both greater and sustained benefit from cognitive retraining.
Read the detailed description
Patients with schizophrenia or schizoaffective disorder who are currently receiving antipsychotic medication will be randomly assigned in a double-blind manner to receive either D-serine (30 mg/kg) or placebo in addition to cognitive rehabilitation or a non-interactive placebo for 12 weeks.
- Conditions
- Schizophrenia, Schizoaffective Disorder
- Being tested
- D-serine, Cognitive Retraining (CRT), Placebo, Cognitive Retraining Placebo
- Medical subject headings
- Schizophrenia, Psychotic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
D-serineDrug
D-serine (30 mg/kg)
Cognitive Retraining (CRT)Behavioural
Cognitive retraining therapy (CRT)
PlaceboDrug
Placebo D-serine Drug
Cognitive Retraining PlaceboBehavioural
Cognitive retraining therapy (CRT) control
| Study group | Role | What they receive |
|---|---|---|
| Drug and control CRT | Experimental | D-serine/control Receives: Drug: D-serine; Behavioral: Cognitive Retraining Placebo |
| Drug and CRT | Experimental | D-serine/cog rehab Receives: Drug: D-serine; Behavioral: Cognitive Retraining (CRT) |
| Placebo Drug and Placebo CRT | Experimental | Placebo/control Receives: Drug: Placebo; Behavioral: Cognitive Retraining Placebo |
| Placebo Drug and CRT | Experimental | Placebo/cog rehab Receives: Behavioral: Cognitive Retraining (CRT); Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Wisconsin Card Sorting Test (WCST)
The WCST allows the clinician to speculate to the following "frontal" lobe functions: strategic planning, organized searching, utilizing environmental feedback to shift cognitive sets, directing behavior toward achieving a goal, and modulating impulsive responding. The test can be administered to those from 6.5 years to 89 years of age.The test takes approximately 12-20 minutes to carry out and generates a number of psychometric scores, including numbers, percentages, and percentiles of: categories achieved, trials, errors, and perseverative errors. Can be interpreted as: the greater the percentage, the greater the measured ability.
Measured: 12 weeks
Hopkins Verbal Learning Test
The Hopkins Verbal Learning Test is designed to assess verbal learning and memory (immediate recall, delayed recall, delayed recognition). The assessment takes approximately 5-10 minutes with a 25-minute delay to complete and 2 minutes to score. The greater the score, the greater the measured recall. The score ranges from 0 to 24.
Measured: 12 weeks
Spatial Span- Total Score
The Spatial Span subtest of the Wechsler Memory Scale can be used as an indicator of working memory and visuospatial processing. An increase in severity of impairment results in a decrease in Spatial Span Total Score. The range is 1 to 28.
Measured: 12 weeks
Positive and Negative Syndrome Scale (PANSS)
The PANSS is a handscored instrument. It uses 25 PANSS items organized into five scales: Negative, Positive, Dysphoric Mood, Activation, and Autistic Preoccupation. The PANSS is based on findings that schizophrenia comprises at least two distinct syndromes. The positive syndrome consists of productive symptoms, while the negative syndrome consists of deficit features. This distinction is useful when developing treatment plans because you can focus on the type of symptoms the patient is experiencing. It is also useful when studying the effects of medication (e.g., in clinical drug trials) because it allows you to determine which type of symptoms are being affected. PANSS Total score minimum = 30, maximum = 210. The greater the score, the greater the symptoms.
Measured: 12 weeks
Secondary outcomes (3)
Heinrichs-Carpenter Quality of Life Scale
The Heinrichs-Carpenter Quality of Life Scale is a testing device. It has a range of possible scores, 0-126 used to evaluate social functioning \& behavior in patients with schizophrenia-lower scores represent poorer mental health.
Measured: 12 weeks
Simpson-Angus Neurological Rating Scale
Simpson-Angus Scale (SAS) is a 10-item rating scale that has been used widely for assessment in both clinical practice and research settings. Items are rated for severity on a 0-4 scale, with definitions given for each anchor point. The highest possible score is 40.
Measured: 12 weeks
UCSD Performance-Based Skills Assessment (UPSA)
The UCSD Performance-Based Skills Assessment (UPSA) is a role-play test designed to evaluate a person's functional capacity in two selected areas of basic living skills. These areas include Finance and Communication. Subjects being tested utilize props to demonstrate how they perform everyday activities and are assessed on their actual performance. The higher the score, the better the performance of an individual. The scores range from 0 to 100.
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 posted12 Oct 2005 (estimated)
- Study startSep 2002
- Primary completionDec 2010
- Study completionSep 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 (3)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 104 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- National Alliance for Research on Schizophrenia and Depression, Donaghue Medical Research Foundation
- Responsible party
- Principal investigator, Deepak C. D'Souza, Yale University
- Investigators
- Deepak C D'Souza, M.D., Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00237809
- Sponsor's protocol ID
- 23594
- Other IDs
- DF01-015
- Status last verified
- Mar 2017
- First submitted
- 13 Sep 2005
- Last updated
- 10 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Tsai GE, Yang P, Chung LC, Tsai IC, Tsai CW, Coyle JT. D-serine added to clozapine for the treatment of schizophrenia. Am J Psychiatry. 1999 Nov;156(11):1822-5. doi: 10.1176/ajp.156.11.1822.
PubMed 10553752Tsai G, Yang P, Chung LC, Lange N, Coyle JT. D-serine added to antipsychotics for the treatment of schizophrenia. Biol Psychiatry. 1998 Dec 1;44(11):1081-9. doi: 10.1016/s0006-3223(98)00279-0.
PubMed 9836012Heresco-Levy U, Javitt DC, Ebstein R, Vass A, Lichtenberg P, Bar G, Catinari S, Ermilov M. D-serine efficacy as add-on pharmacotherapy to risperidone and olanzapine for treatment-refractory schizophrenia. Biol Psychiatry. 2005 Mar 15;57(6):577-85. doi: 10.1016/j.biopsych.2004.12.037.
PubMed 15780844
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- D-Serine Treatment of Negative Symptoms and Cognitive Deficits in Schizophrenia
- ClinicalTrials.gov ID
- NCT00237809
- Acronym / sponsor ID
- 23594
- Conditions
- Schizophrenia, Schizoaffective Disorder
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 104 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Alliance for Research on Schizophrenia and Depression, Donaghue Medical Research Foundation
- Study start
- Sep 2002
- Primary completion
- Dec 2010 (actual)
- Study completion
- Sep 2012 (actual)
- First posted
- 12 Oct 2005 (estimated)
- Results
- Posted 10 May 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is based on the hypothesis that by increasing N-methyl-D-aspartic acid (NMDA) receptor function in the brain and thereby increasing the capacity of the brain to both form new connections and strengthen existing connections, schizophrenic patients may derive both greater and sustained benefit from cognitive retraining.
Detailed description
Patients with schizophrenia or schizoaffective disorder who are currently receiving antipsychotic medication will be randomly assigned in a double-blind manner to receive either D-serine (30 mg/kg) or placebo in addition to cognitive rehabilitation or a non-interactive placebo for 12 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Drug and control CRT | Experimental | Drug: D-serine, Behavioral: Cognitive Retraining PlaceboD-serine/control |
| Drug and CRT | Experimental | Drug: D-serine, Behavioral: Cognitive Retraining (CRT)D-serine/cog rehab |
| Placebo Drug and Placebo CRT | Experimental | Drug: Placebo, Behavioral: Cognitive Retraining PlaceboPlacebo/control |
| Placebo Drug and CRT | Experimental | Behavioral: Cognitive Retraining (CRT), Drug: PlaceboPlacebo/cog rehab |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Diagnosis of schizophrenia or schizoaffective disorder
Key exclusion criteria (1 listed)
- 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-serineD-serine (30 mg/kg) | Drug | Drug and CRT, Drug and control CRT |
| Cognitive Retraining (CRT)Cognitive retraining therapy (CRT) | Behavioural | Drug and CRT, Placebo Drug and CRT |
| PlaceboPlacebo D-serine Drug | Drug | Placebo Drug and CRT, Placebo Drug and Placebo CRT |
| Cognitive Retraining PlaceboCognitive retraining therapy (CRT) control | Behavioural | Drug and control CRT, Placebo Drug and Placebo CRT |
Primary outcome
Wisconsin Card Sorting Test (WCST)
Time frame: 12 weeks
The WCST allows the clinician to speculate to the following "frontal" lobe functions: strategic planning, organized searching, utilizing environmental feedback to shift cognitive sets, directing behavior toward achieving a goal, and modulating impulsive responding. The test can be administered to those from 6.5 years to 89 years of age.The test takes approximately 12-20 minutes to carry out and generates a number of psychometric scores, including numbers, percentages, and percentiles of: categories achieved, trials, errors, and perseverative errors. Can be interpreted as: the greater the percentage, the greater the measured ability.
Hopkins Verbal Learning Test
Time frame: 12 weeks
The Hopkins Verbal Learning Test is designed to assess verbal learning and memory (immediate recall, delayed recall, delayed recognition). The assessment takes approximately 5-10 minutes with a 25-minute delay to complete and 2 minutes to score. The greater the score, the greater the measured recall. The score ranges from 0 to 24.
Spatial Span- Total Score
Time frame: 12 weeks
The Spatial Span subtest of the Wechsler Memory Scale can be used as an indicator of working memory and visuospatial processing. An increase in severity of impairment results in a decrease in Spatial Span Total Score. The range is 1 to 28.
Positive and Negative Syndrome Scale (PANSS)
Time frame: 12 weeks
The PANSS is a handscored instrument. It uses 25 PANSS items organized into five scales: Negative, Positive, Dysphoric Mood, Activation, and Autistic Preoccupation. The PANSS is based on findings that schizophrenia comprises at least two distinct syndromes. The positive syndrome consists of productive symptoms, while the negative syndrome consists of deficit features. This distinction is useful when developing treatment plans because you can focus on the type of symptoms the patient is experiencing. It is also useful when studying the effects of medication (e.g., in clinical drug trials) because it allows you to determine which type of symptoms are being affected. PANSS Total score minimum = 30, maximum = 210. The greater the score, the greater the symptoms.
3 secondary outcomes
Heinrichs-Carpenter Quality of Life Scale
Time frame: 12 weeks
Simpson-Angus Neurological Rating Scale
Time frame: 12 weeks
UCSD Performance-Based Skills Assessment (UPSA)
Time frame: 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 10553752Tsai GE, Yang P, Chung LC, Tsai IC, Tsai CW, Coyle JT. D-serine added to clozapine for the treatment of schizophrenia. Am J Psychiatry. 1999 Nov;156(11):1822-5. doi: 10.1176/ajp.156.11.1822.
- Background: PubMed 9836012Tsai G, Yang P, Chung LC, Lange N, Coyle JT. D-serine added to antipsychotics for the treatment of schizophrenia. Biol Psychiatry. 1998 Dec 1;44(11):1081-9. doi: 10.1016/s0006-3223(98)00279-0.
- Background: PubMed 15780844Heresco-Levy U, Javitt DC, Ebstein R, Vass A, Lichtenberg P, Bar G, Catinari S, Ermilov M. D-serine efficacy as add-on pharmacotherapy to risperidone and olanzapine for treatment-refractory schizophrenia. Biol Psychiatry. 2005 Mar 15;57(6):577-85. doi: 10.1016/j.biopsych.2004.12.037.
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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.
Deepak C D'Souza, M.D. principal investigator
Yale University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing D-serine and Cognitive Retraining (CRT) in people with Schizophrenia and Schizoaffective Disorder, run by Yale University at 2 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 1 inclusion and 1 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 10 May 2017. 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 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 10 May 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?
Wisconsin Card Sorting Test (WCST) (time frame: 12 weeks). The study lists 4 primary outcomes in all. 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 NCT00237809, which also lists 3 linked publications.
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 10 May 2017.