SchizophreniaPhase 3NCT00000371
Trial of D-Cycloserine in Schizophrenia
A Phase 3 study testing D-cycloserine in people with Schizophrenia, run by Massachusetts General Hospital.
Trial summary
To characterize further the effects of D-cycloserine augmentation of antipsychotic treatment on negative symptoms, performance on neurocognitive tasks, and on markers for glutamatergic, dopaminergic and serotonergic function in serum and cerebrospinal fluid. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- D-cycloserine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- No sites listed yet
- Study dates
- Aug 1996to Apr 2002
- 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 as per DSM IV criteria
- Have been treated for at least 6 months with any conventional neuroleptic
- Have prominent negative symptoms as defined by a total score of 40 or greater on the scale for the assessment of negative symptoms (SANS)
Who cannot join
- Active alcohol or drug abuse
- Unstable Medical Illness, seizure disorder, or other serious neurological disorder
- Pregnant or Nursing
- Unable to complete a cognitive battery
About this study
Official title: A Six Month, Placebo-Controlled Trial of D-Cycloserine Co-Administered With Conventional Antipsychotics in Schizophrenia Patients
To characterize further the effects of D-cycloserine augmentation of antipsychotic treatment on negative symptoms, performance on neurocognitive tasks, and on markers for glutamatergic, dopaminergic and serotonergic function in serum and cerebrospinal fluid. To determine if negative symptoms and cognitive function improve over time, if these improvements meaningfully impact quality of life factors, if they correlate with markers of neuronal function, and if subpopulations can be identified according to response.
Dysfunction of glutamatergic neuronal systems has recently been implicated in the pathophysiology of schizophrenia based on the finding that non-competitive inhibitors of the NMDA receptor can reproduce in normals the positive symptoms, negative symptoms, and cognitive deficits of schizophrenia. Furthermore, glutamatergic dysfunction may alter forebrain dopaminergic neuronal activity, a system central to the antipsychotic action of typical neuroleptics. It is believed that enhancing NMDA receptor function by systemic treatment with D-cycloserine, a partial agonist at the glycine modulatory site of the NMDA receptor, will reduce symptoms in schizophrenia.
Sixty schizophrenic outpatients with prominent, primary negative symptoms are treated with antipsychotic medication and are randomly assigned to D-cycloserine or placebo for a 6-month, fixed-dose trial. The primary outcome measure is the total score on the Scale for Assessment of Negative Symptoms (SANS). A neuropsychological battery, which emphasizes tests sensitive to prefrontal cortical function, is administered. Blood is obtained at several time points and CSF is obtained at Week 8 for assay of concentrations of D-cycloserine, glutamate, HVA, and 5HIAA.
Read the detailed description
To characterize further the effects of D-cycloserine augmentation of antipsychotic treatment on negative symptoms, performance on neurocognitive tasks, and on markers for glutamatergic, dopaminergic, and serotonergic function in serum and cerebrospinal fluid. To determine if negative symptoms and cognitive function improve over time, if these improvements meaningfully impact quality of life factors, if they correlate with markers of neuronal function, and if subpopulations can be identified according to response.
Dysfunction of glutamatergic neuronal systems has recently been implicated in the pathophysiology of schizophrenia based on the finding that non-competitive inhibitors of the NMDA receptor can reproduce in normals the positive symptoms, negative symptoms and cognitive deficits of schizophrenia. Furthermore, glutamatergic dysfunction may alter forebrain dopaminergic neuronal activity, a system central to the antipsychotic action of typical neuroleptics. It is believed that enhancing NMDA receptor function by systemic treatment with D-cycloserine, a partial agonist at the glycine modulatory site of the NMDA receptor, will reduce symptoms in schizophrenia.
Sixty schizophrenic outpatients with prominent, primary negative symptoms are treated with antipsychotic medication and are randomly assigned to D-cycloserine or placebo for a 6-month, fixed-dose trial. The primary outcome measure is the total score on the Scale for Assessment of Negative Symptoms (SANS). A neuropsychological battery, which emphasizes tests sensitive to prefrontal cortical function, is administered. Blood is obtained at several time points and CSF is obtained at Week 8 for assay of concentrations of D-cycloserine, glutamate, HVA, and 5HIAA.
- Conditions
- Schizophrenia
- Being tested
- D-cycloserine, Placebo
- Keywords
- Adult, Cognition, Cycloserine, Dopamine, Female, Glutamic Acid, Human, Male, Receptors, N-Methyl-D-Aspartate, Schizophrenia, Serotonin, Quality of Life, Cycloserine -- *therapeutic use, Dopamine -- blood, Dopamine -- cerebrospinal fluid, Glutamic Acid -- blood, Glutamic Acid -- cerebrospinal fluid, Serotonin -- blood, Serotonin -- cerebrospinal fluid
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
D-cycloserineDrug
Also called Cycloserine
50 mg/daily by mouth
PlaceboDrug
50 mg/day of placebo by mouth
| Study group | Role | What they receive |
|---|---|---|
| D-Cycloserine | Experimental | Subjects were given 50 mg/day of D-Cycloserine for 24 weeks Receives: Drug: D-cycloserine |
| Placebo | Placebo comparator | Participants were given 50 mg/day of Placebo for 24 weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Scale for the Assessment of Negative Symptoms (SANS)
The slope of SANS total score from baseline to week 8 in the treatment and placebo groups on the scale for the assessment of negative symptoms (SANS) total score. Total SANS scores range from 0-100. The SANS is comprised of 5 subscores: Affective Flattening or Blunting (score range 0-35), Alogia (score range 0-20), Avolition-Apathy (score range 0-15), Anhedonia-Asociality (score range 0-20), and Attention (0-10). For each scale, the higher the score the more prominent the negative symptoms were. The slopes were obtained by plotting the group SANS total score mean for treatment vs. placebo on Baseline, Week 4, and Week 8 and performing a random slopes model.
Measured: Baseline, Week 4, Week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 1999 (estimated)
- Study startAug 1996
- Primary completionApr 2002
- Study completionApr 2002
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.
- More trials run by Massachusetts General HospitalThe 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Donald C. Goff, MD, Massachusetts General Hospital
- Investigators
- Donald Goff, MD, Principal investigator
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00000371
- Sponsor's protocol ID
- R01MH054245-01A2
- Status last verified
- Sep 2014
- First submitted
- 2 Nov 1999
- Last updated
- 10 Sep 2014
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Goff DC, Herz L, Posever T, Shih V, Tsai G, Henderson DC, Freudenreich O, Evins AE, Yovel I, Zhang H, Schoenfeld D. A six-month, placebo-controlled trial of D-cycloserine co-administered with conventional antipsychotics in schizophrenia patients. Psychopharmacology (Berl). 2005 Apr;179(1):144-50. doi: 10.1007/s00213-004-2032-2. Epub 2004 Oct 21.
PubMed 15502972
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Six Month, Placebo-Controlled Trial of D-Cycloserine Co-Administered With Conventional Antipsychotics in Schizophrenia Patients
- ClinicalTrials.gov ID
- NCT00000371
- Acronym / sponsor ID
- R01MH054245-01A2
- Conditions
- Schizophrenia
- Keywords
- Adult, Cognition, Cycloserine, Dopamine, Female, Glutamic Acid, Human, Male
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- Aug 1996
- Primary completion
- Apr 2002 (actual)
- Study completion
- Apr 2002 (actual)
- First posted
- 3 Nov 1999 (estimated)
- Results
- Posted 10 Sep 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To characterize further the effects of D-cycloserine augmentation of antipsychotic treatment on negative symptoms, performance on neurocognitive tasks, and on markers for glutamatergic, dopaminergic and serotonergic function in serum and cerebrospinal fluid. To determine if negative symptoms and cognitive function improve over time, if these improvements meaningfully impact quality of life factors, if they correlate with markers of neuronal function, and if subpopulations can be identified according to response.
Dysfunction of glutamatergic neuronal systems has recently been implicated in the pathophysiology of schizophrenia based on the finding that non-competitive inhibitors of the NMDA receptor can reproduce in normals the positive symptoms, negative symptoms, and cognitive deficits of schizophrenia. Furthermore, glutamatergic dysfunction may alter forebrain dopaminergic neuronal activity, a system central to the antipsychotic action of typical neuroleptics. It is believed that enhancing NMDA receptor function by systemic treatment with D-cycloserine, a partial agonist at the glycine modulatory site of the NMDA receptor, will reduce symptoms in schizophrenia.
Sixty schizophrenic outpatients with prominent, primary negative symptoms are treated with antipsychotic medication and are randomly assigned to D-cycloserine or placebo for a 6-month, fixed-dose trial. The primary outcome measure is the total score on the Scale for Assessment of Negative Symptoms (SANS). A neuropsychological battery, which emphasizes tests sensitive to prefrontal cortical function, is administered. Blood is obtained at several time points and CSF is obtained at Week 8 for assay of concentrations of D-cycloserine, glutamate, HVA, and 5HIAA.
Detailed description
To characterize further the effects of D-cycloserine augmentation of antipsychotic treatment on negative symptoms, performance on neurocognitive tasks, and on markers for glutamatergic, dopaminergic, and serotonergic function in serum and cerebrospinal fluid. To determine if negative symptoms and cognitive function improve over time, if these improvements meaningfully impact quality of life factors, if they correlate with markers of neuronal function, and if subpopulations can be identified according to response.
Dysfunction of glutamatergic neuronal systems has recently been implicated in the pathophysiology of schizophrenia based on the finding that non-competitive inhibitors of the NMDA receptor can reproduce in normals the positive symptoms, negative symptoms and cognitive deficits of schizophrenia. Furthermore, glutamatergic dysfunction may alter forebrain dopaminergic neuronal activity, a system central to the antipsychotic action of typical neuroleptics. It is believed that enhancing NMDA receptor function by systemic treatment with D-cycloserine, a partial agonist at the glycine modulatory site of the NMDA receptor, will reduce symptoms in schizophrenia.
Sixty schizophrenic outpatients with prominent, primary negative symptoms are treated with antipsychotic medication and are randomly assigned to D-cycloserine or placebo for a 6-month, fixed-dose trial. The primary outcome measure is the total score on the Scale for Assessment of Negative Symptoms (SANS). A neuropsychological battery, which emphasizes tests sensitive to prefrontal cortical function, is administered. Blood is obtained at several time points and CSF is obtained at Week 8 for assay of concentrations of D-cycloserine, glutamate, HVA, and 5HIAA.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| D-Cycloserine | Experimental | Drug: D-cycloserineSubjects were given 50 mg/day of D-Cycloserine for 24 weeks |
| Placebo | Placebo comparator | Drug: PlaceboParticipants were given 50 mg/day of Placebo for 24 weeks. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Diagnosis of Schizophrenia as per DSM IV criteria
- Have been treated for at least 6 months with any conventional neuroleptic
- Have prominent negative symptoms as defined by a total score of 40 or greater on the scale for the assessment of negative symptoms (SANS)
Key exclusion criteria (4 listed)
- Active alcohol or drug abuse
- Unstable Medical Illness, seizure disorder, or other serious neurological disorder
- Pregnant or Nursing
- Unable to complete a cognitive battery
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-cycloserineAlso: Cycloserine50 mg/daily by mouth | Drug | D-Cycloserine |
| Placebo50 mg/day of placebo by mouth | Drug | Placebo |
Primary outcome
Scale for the Assessment of Negative Symptoms (SANS)
Time frame: Baseline, Week 4, Week 8
The slope of SANS total score from baseline to week 8 in the treatment and placebo groups on the scale for the assessment of negative symptoms (SANS) total score. Total SANS scores range from 0-100. The SANS is comprised of 5 subscores: Affective Flattening or Blunting (score range 0-35), Alogia (score range 0-20), Avolition-Apathy (score range 0-15), Anhedonia-Asociality (score range 0-20), and Attention (0-10). For each scale, the higher the score the more prominent the negative symptoms were. The slopes were obtained by plotting the group SANS total score mean for treatment vs. placebo on Baseline, Week 4, and Week 8 and performing a random slopes model.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 15502972Goff DC, Herz L, Posever T, Shih V, Tsai G, Henderson DC, Freudenreich O, Evins AE, Yovel I, Zhang H, Schoenfeld D. A six-month, placebo-controlled trial of D-cycloserine co-administered with conventional antipsychotics in schizophrenia patients. Psychopharmacology (Berl). 2005 Apr;179(1):144-50. doi: 10.1007/s00213-004-2032-2. Epub 2004 Oct 21.
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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.
Donald Goff, MD principal investigator
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing D-cycloserine in people with Schizophrenia, run by Massachusetts General Hospital.
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 3 inclusion and 4 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 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.
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 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 Sep 2014). 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 for the Assessment of Negative Symptoms (SANS) (time frame: Baseline, Week 4, Week 8). 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 NCT00000371, 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 10 Sep 2014.