SchizophreniaNCT00963924
D-cycloserine Augmentation of Cognitive Remediation in Schizophrenia
A study testing D-cycloserine and Cognitive Remediation in people with Schizophrenia, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
This study seeks to examine the effects of D-cycloserine augmentation on cognitive remediation for patients diagnosed with schizophrenia. We will test the hypotheses that D-cycloserine will significantly improve cognitive performance, negative symptoms, and measures of functioning compared to placebo when combined… 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 and Cognitive Remediation
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 54 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2009to Jun 2011
- Phase
- Interventional
- 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
- Male or female
- Age 18-65 years
- Diagnosis of schizophrenia or schizoaffective disorder, depressed type
- Stable dose of antipsychotic for at least 4 weeks
- Able to provide informed consent
- Able to complete a cognitive battery
- Able to perform the cognitive remediation exercises
Who cannot join
- Current treatment with clozapine
- Dementia
- Seizure disorder
- Unstable medical illness
- Renal insufficiency measured as eGFR >60mg/dL/min
- Active substance abuse: positive urine toxic screen
- Pregnancy, nursing, or unwilling to use appropriate birth control measures during participation if female and fertile.
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Official title: A Placebo-controlled Trial of D-cycloserine Augmentation of Cognitive Remediation in Schizophrenia
This study seeks to examine the effects of D-cycloserine augmentation on cognitive remediation for patients diagnosed with schizophrenia. We will test the hypotheses that D-cycloserine will significantly improve cognitive performance, negative symptoms, and measures of functioning compared to placebo when combined with eight weeks of cognitive remediation. We expect that these effects will persist when assessed at six-month follow up.
Read the detailed description
D-cycloserine has been shown to enhance learning in animal models and, in a previous trial, once-weekly D-cycloserine improved negative symptoms in schizophrenia subjects. We set out to test whether DCS combined with cognitive remediation would improve learning of a practiced auditory discrimination task and whether gains would generalize to unpracticed cognitive tasks.
The proposed study consists of an 8-week, placebo-controlled, double-blind, parallel-group trial of D-cycloserine augmentation of cognitive remediation in schizophrenia outpatients. The primary outcome measure is change in performance on the MATRICS cognitive battery composite score after 8 weeks. Secondary outcome measures include a measure of processing speed assessed after weeks 1, 2, 4 \& 8, and changes in negative symptoms and measures of functioning after 4 and 8 weeks. In addition, all outcome measures will be repeated at 6 months to assess persistence of benefit.
Hypotheses:
- D-cycloserine will significantly improve cognitive performance as measured by the composite score on the MATRICS battery compared to placebo after 8 weeks of cognitive remediation.
- D-cycloserine will significantly improve negative symptoms as measured by the SANS compared to placebo after 8 weeks when combined with cognitive remediation.
- D-cycloserine will significantly improve measures of functioning (GAS, QoL and CGI) at 8 weeks compared to placebo when combined with cognitive remediation.
- D-cycloserine effects on cognition, negative symptoms and functioning will persist compared to placebo when assessed at 6-month follow-up.
- Conditions
- Schizophrenia
- Being tested
- D-cycloserine, Placebo, Cognitive Remediation
- Keywords
- Cognitive Impairment, Neuroplasticity, D-cycloserine, NMDA, Anti-Bacterial Agents, Mental Disorders, Psychotic Disorders, Antitubercular Agents, Schizophrenia and Disorders with Psychotic Features, Schizoaffective Disorder
- Medical subject headings
- Schizophrenia, Cognitive Dysfunction, Mental Disorders, Psychotic Disorders, Schizophrenia Spectrum and Other Psychotic Disorders
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 by mouth one hour before first cognitive remediation session each week for eight weeks.
PlaceboDrug
Placebo by mouth one hour before first cognitive remediation session each week for eight weeks.
Cognitive RemediationBehavioural
Also called Brain Fitness Program
40 one-hour daily sessions of cognitive remediation (Brain Fitness Program) over eight weeks.
| Study group | Role | What they receive |
|---|---|---|
| D-cycloserine | Experimental | Participants will receive D-cycloserine weekly, one hour before the first cognitive remediation session of the week, for eight weeks. Receives: Drug: D-cycloserine; Behavioral: Cognitive Remediation |
| Placebo | Placebo comparator | Participants will receive placebo weekly, one hour before the first cognitive remediation session of the week, for eight weeks. Receives: Drug: Placebo; Behavioral: Cognitive Remediation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS)
Change of a composite score from baseline to week 8 on the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS). The MATRICS consists of 10 cognitive tasks that are used to calculate scores in 7 cognitive domains: speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. The raw scores on each cognitive task are transformed on a normative scale into t-scores, and then these scores are combined to calculate the domain scores. The composite score is calculated by averaging all domain t-scores to come up with one overall cognitive composite t-score. For all scores on the assessment, the higher the score the better the performance on the task.
Measured: Baseline vs. Week 8
Scale for Assessment of Negative Symptoms (SANS)
The total scores from baseline and week 8 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 total score was computed by adding all the sub-scale total scores. Scores are reported for baseline and week 8.
Measured: Baseline vs. Week 8
Auditory Discrimination Task: Interstimulus Interval (ISI)
The auditory discrimination task involved trials in which the subject differentiated between rapidly-presented frequency-modulated sweeps separated by a short interstimulus interval (ISI). In this task, sustained successful performance is more difficult with shorter stimulus presentations and ISIs (which were equal within a trial). Thus, our dependent measure was the shortest stimulus duration/ISI, in ms, for trials in which subjects were able to perform the task at 85% accuracy, referred to as ISI for simplicity. The shorter the score the better the performance on the task. Scores are reported for baseline and week 8.
Measured: Baseline vs. Week 8
Secondary outcomes (6)
Positive and Negative Syndrome Scale (PANSS)
The baseline score on the positive symptom sub-scale of the Positive and Negative Syndrome Scale (PANSS). Total PANSS positive symptom sub-scale scores range from 7-49. The PANSS positive symptom sub-scale is comprised of 7 items rated on a scale of 1-7: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. A score of one on each item 1 absent, 2 is minimal, 3 is mild, 4 is moderate, 5 is moderately severe, 6 is severe, and 7 is extreme. The total score was computed by adding all the items on the sub-scale together. The higher a score the more prominent a positive symptom is.
Measured: Baseline
Global Assessment of Functioning Scale (GAS)
The Global Assessment of Functioning Scale (GAS) measured at baseline. This scale measures social, occupational, and psychological functioning, on a scale of 0-100. The higher the score, the greater a participant's functioning level.
Measured: Baseline
Heinrich Quality of Life Scale (QoL)
Baseline scores of the Heinrich Quality of Life Scale, a 21 item scale designed and validated to measure intrapsychic foundations, interpersonal relations, instrumental role, and common objects and activities in patients diagnosed with Schizophrenia. Patients are rated on each of the 21 items on a scale of 0-6. Total scores are computed by adding up the scores of each individual item, with a total score ranging from 0-126. Higher scores reflect higher functioning.
Measured: Baseline
Calgary Depression Scale for Schizophrenia (CDSS)
Baseline scores on the Calgary Depression Scale for Schizophrenia (CDSS). Total CDSS scores range from 0-27. The assessment is comprised of 9 questions covering the topics of Depression, Hopelessness, Self Depreciation, Guilty Ideas of Reference, Pathological Guilt, Morning Depression, Early Wakening, Suicide, Observed Depression. Each item is scored on a scale from 0-3 (0 = absent, 1 = mild, 2 = moderate, 3 = severe). The total score is computed by adding up the individual scores of each item. The higher the score, the more prominent the symptoms of depression are for the participant.
Measured: Baseline
Clinical Global Impression (CGI)
Considering you total clinical experience with this patient population, how mentally ill is the patient at this time?
1=Normal, not at all, 2=Borderline mentally ill, 3=Mildy ill, 4=Moderately ill, 5=Markedly ill, 6=Severely ill, 7=Among the most extremely ill patients; a higher score indicates worse outcome
Measured: Weeks 0 and 8, and Month 6 after cognitive remediation completion
Side Effects Checklist (SEC)
Each side effect is entered as either yes or no for having had any severity of the side effect at each visit.
Measured: Weeks 0 - 8, and Month 6 after cognitive remediation completion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2009 (estimated)
- Study startAug 2009
- Primary completionMay 2011
- Study completionJun 2011
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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Donald C. Goff, MD, Massachusetts General Hospital
- Investigators
- Donald C. Goff, M.D., Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00963924
- Sponsor's protocol ID
- 2008P002237
- Other IDs
- 5P50MH060450, DATR A3-NSC
- Status last verified
- Jan 2018
- First submitted
- 20 Aug 2009
- Last updated
- 6 Feb 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Cain CK, McCue M, Bello I, Creedon T, Tang DI, Laska E, Goff DC. d-Cycloserine augmentation of cognitive remediation in schizophrenia. Schizophr Res. 2014 Mar;153(1-3):177-83. doi: 10.1016/j.schres.2014.01.016. Epub 2014 Jan 30.
PubMed 24485587
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Placebo-controlled Trial of D-cycloserine Augmentation of Cognitive Remediation in Schizophrenia
- ClinicalTrials.gov ID
- NCT00963924
- Acronym / sponsor ID
- 2008P002237
- Conditions
- Schizophrenia
- Keywords
- Cognitive Impairment, Neuroplasticity, D-cycloserine, NMDA, Anti-Bacterial Agents, Mental Disorders, Psychotic Disorders, Antitubercular Agents
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Aug 2009
- Primary completion
- May 2011 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 24 Aug 2009 (estimated)
- Results
- Posted 20 Aug 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study seeks to examine the effects of D-cycloserine augmentation on cognitive remediation for patients diagnosed with schizophrenia. We will test the hypotheses that D-cycloserine will significantly improve cognitive performance, negative symptoms, and measures of functioning compared to placebo when combined with eight weeks of cognitive remediation. We expect that these effects will persist when assessed at six-month follow up.
Detailed description
D-cycloserine has been shown to enhance learning in animal models and, in a previous trial, once-weekly D-cycloserine improved negative symptoms in schizophrenia subjects. We set out to test whether DCS combined with cognitive remediation would improve learning of a practiced auditory discrimination task and whether gains would generalize to unpracticed cognitive tasks.
The proposed study consists of an 8-week, placebo-controlled, double-blind, parallel-group trial of D-cycloserine augmentation of cognitive remediation in schizophrenia outpatients. The primary outcome measure is change in performance on the MATRICS cognitive battery composite score after 8 weeks. Secondary outcome measures include a measure of processing speed assessed after weeks 1, 2, 4 \& 8, and changes in negative symptoms and measures of functioning after 4 and 8 weeks. In addition, all outcome measures will be repeated at 6 months to assess persistence of benefit.
Hypotheses:
- D-cycloserine will significantly improve cognitive performance as measured by the composite score on the MATRICS battery compared to placebo after 8 weeks of cognitive remediation.
- D-cycloserine will significantly improve negative symptoms as measured by the SANS compared to placebo after 8 weeks when combined with cognitive remediation.
- D-cycloserine will significantly improve measures of functioning (GAS, QoL and CGI) at 8 weeks compared to placebo when combined with cognitive remediation.
- D-cycloserine effects on cognition, negative symptoms and functioning will persist compared to placebo when assessed at 6-month follow-up.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| D-cycloserine | Experimental | Drug: D-cycloserine, Behavioral: Cognitive RemediationParticipants will receive D-cycloserine weekly, one hour before the first cognitive remediation session of the week, for eight weeks. |
| Placebo | Placebo comparator | Drug: Placebo, Behavioral: Cognitive RemediationParticipants will receive placebo weekly, one hour before the first cognitive remediation session of the week, for eight weeks. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male or female
- Age 18-65 years
- Diagnosis of schizophrenia or schizoaffective disorder, depressed type
- Stable dose of antipsychotic for at least 4 weeks
- Able to provide informed consent
Key exclusion criteria (7 listed)
- Current treatment with clozapine
- Dementia
- Seizure disorder
- Unstable medical illness
- Renal insufficiency measured as eGFR >60mg/dL/min
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 by mouth one hour before first cognitive remediation session each week for eight weeks. | Drug | D-cycloserine |
| PlaceboPlacebo by mouth one hour before first cognitive remediation session each week for eight weeks. | Drug | Placebo |
| Cognitive RemediationAlso: Brain Fitness Program40 one-hour daily sessions of cognitive remediation (Brain Fitness Program) over eight weeks. | Behavioural | D-cycloserine, Placebo |
Primary outcome
Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS)
Time frame: Baseline vs. Week 8
Change of a composite score from baseline to week 8 on the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS). The MATRICS consists of 10 cognitive tasks that are used to calculate scores in 7 cognitive domains: speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. The raw scores on each cognitive task are transformed on a normative scale into t-scores, and then these scores are combined to calculate the domain scores. The composite score is calculated by averaging all domain t-scores to come up with one overall cognitive composite t-score. For all scores on the assessment, the higher the score the better the performance on the task.
Scale for Assessment of Negative Symptoms (SANS)
Time frame: Baseline vs. Week 8
The total scores from baseline and week 8 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 total score was computed by adding all the sub-scale total scores. Scores are reported for baseline and week 8.
Auditory Discrimination Task: Interstimulus Interval (ISI)
Time frame: Baseline vs. Week 8
The auditory discrimination task involved trials in which the subject differentiated between rapidly-presented frequency-modulated sweeps separated by a short interstimulus interval (ISI). In this task, sustained successful performance is more difficult with shorter stimulus presentations and ISIs (which were equal within a trial). Thus, our dependent measure was the shortest stimulus duration/ISI, in ms, for trials in which subjects were able to perform the task at 85% accuracy, referred to as ISI for simplicity. The shorter the score the better the performance on the task. Scores are reported for baseline and week 8.
6 secondary outcomes
Positive and Negative Syndrome Scale (PANSS)
Time frame: Baseline
Global Assessment of Functioning Scale (GAS)
Time frame: Baseline
Heinrich Quality of Life Scale (QoL)
Time frame: Baseline
Calgary Depression Scale for Schizophrenia (CDSS)
Time frame: Baseline
Clinical Global Impression (CGI)
Time frame: Weeks 0 and 8, and Month 6 after cognitive remediation completion
Side Effects Checklist (SEC)
Time frame: Weeks 0 - 8, and Month 6 after cognitive remediation completion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 24485587Cain CK, McCue M, Bello I, Creedon T, Tang DI, Laska E, Goff DC. d-Cycloserine augmentation of cognitive remediation in schizophrenia. Schizophr Res. 2014 Mar;153(1-3):177-83. doi: 10.1016/j.schres.2014.01.016. Epub 2014 Jan 30.
Related trials for Schizophrenia
RecruitingPhase 3
A Study to Evaluate the Long-term Safety and Tolerability of Xanomeline and Trospium Chloride for the Treatment of Psychiatric Disorders in Children and Adolescents
Schizophrenia, Autism-Related Irritability
Not yet recruiting
Deep Brain Stimulation for Treatment-Resistant Schizophrenia
Treatment Resistant Disorders
Not yet recruitingObservational study
Sleep Monitoring for Early Detection of Relapse in People With Schizophrenia or Bipolar Disorder Receiving Usual Treatment
Bipolar Disorder (BD), SCHIZOPHRENIA 1 (Disorder)
Not yet recruitingPhase 1
Pharmacokinetics and Relative Bioavailability of Intranasal vs Intramuscular Olanzapine in Healthy Adult Participants
Healthy Adult Participants
Active, not recruiting
Designing and Evaluating a Classroom-Based Mental Health Programme for Adolescents.
Mental Health Promotion
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 C. Goff, M.D. principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing D-cycloserine and Cognitive Remediation in people with Schizophrenia, run by Massachusetts General Hospital at 1 site 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 7 inclusion and 7 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 6 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Aug 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?
Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) (time frame: Baseline vs. Week 8). The study lists 3 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 NCT00963924, 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 6 Feb 2018.