SchizophreniaPhase 3NCT00167362
Cognitive Enhancement Therapy for Early-Stage Schizophrenia
A Phase 3 study testing Cognitive enhancement therapy (CET) and Enriched supportive therapy (EST) in people with Schizophrenia, run by Beth Israel Deaconess Medical Center at 1 site in United States.
Trial summary
This study will determine the effectiveness of cognitive enhancement therapy (CET) in treating cognitive abnormalities in people experiencing the early stages of schizophrenia. Read more about this study
- Who is it for?
- Ages 16 to 51 yearsHealthy volunteers can take part
- Conditions the study is for
- Schizophrenia
- What is being tested?
- Cognitive enhancement therapy (CET) and Enriched supportive therapy (EST)
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 67 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2001to Dec 2016
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 16 to 51 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- DSM-IV diagnosis of schizophrenia, schizoaffective or schizophreniform disorder at the time of initial assessment
- Pre-treatment illness duration an average of 5 years, not to exceed 8 years
- Stable positive symptoms (e.g., if present do not grossly interfere with behavior such as command hallucinations or delusions)
- Currently maintained and compliant with prescribed antipsychotic medication
- Socially and cognitively disabled, e.g., meet criteria on a Cognitive Style Scale (score greater than or equal to 7), and Social Cognition Disability Scale (score greater than or equal to 12).
Who cannot join
- Alcohol/drug abuse or dependence that has significantly interfered with adjustment in the past two months (e.g., patients currently undergoing D and A treatment must successfully complete their recovery program prior to referral)
- Organic brain syndrome, including HIV illness (due to its effect on CNS function)
- IQ below 80 or language skills below the sixth grade level
- Medical contraindications that preclude an appropriate antipsychotic medication
- Persistent suicidality
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
About this study
Official title: Rehabilitation, Brain Function and Early Schizophrenia
This study will determine the effectiveness of cognitive enhancement therapy (CET) in treating cognitive abnormalities in people experiencing the early stages of schizophrenia.
Read the detailed description
In this study, we wish to determine the neurobiological predictors and the relative efficacy of Cognitive Enhancement Therapy (CET) in ameliorating specific cognitive abnormalities presumably mediated by PFC and related brain structures, among younger, early-course schizophrenia patients who potentially have a better prognosis. A series of recent-onset schizophrenic patients, whose psychotic symptoms have successfully been stabilized on an atypical antipsychotic drug for one year following initiation of treatment, will be randomized to CET combined with an enriched supportive therapy (EST) or EST alone, and treated for two years. Subjects will have been assessed on neurobehavioral and clinical indices immediately prior to beginning CET or EST (corresponding with the CNMD 1-year follow-up) and in the proposed study will again be assessed after 1 and 2 years of psychosocial treatment. In a smaller subset of patients, we will also seek to collect preliminary data on the efficacy of CET in reversing the neurobiological alterations in the PFC. The hypotheses of this study are:
- The presence of relatively well preserved PFC structure and function (PFC volume, activation with fMRI, and metabolism as measured by proton MRS) at baseline will predict a better response to CET (Neurobiological Prediction Hypothesis).
- CET combined with "enriched" supportive psychotherapy (EST) will be more effective than EST alone in ameliorating social and non-social cognitive deficits of patients with early schizophrenic illness whose psychotic symptoms have been stabilized on maintenance chemotherapy (The Treatment Efficacy Hypothesis).
- CET will result in additive, positive effects on neurocognitive parameters that were not observed following one year of antipsychotic medication, using a "sequential" treatment design in a subset of patients in whom we have pre-neuroleptic baseline data from CNMD studies (The Treatment Specificity Hypothesis).
Study Design: Subjects will be randomly assigned, once stabilized clinically, to CET plus EST (n = 30) or EST alone (n = 30) and then treated for up to two years. Clinical, neuropsychological, neurological and functional neuroimaging assessments will be administered at baseline and at two annual follow-ups. At the end of CET or EST treatment, subjects will be asked to come back quarterly to meet informally with either their Cognitive Enhancement Therapy clinicians and former group members, or with their Enriched Supportive Therapy clinician. The purpose of these visits is for us to learn more about the successes that patients have had, or about the difficulties that they might have had since leaving the program. Clinician(s) will also share information obtained during this follow-up which might help patient in overcoming these difficulties. At the end of the one-year period post EST or CET treatment, subjects will be assessed on all measures, except for diagnostic, imaging and blood studies.
- Conditions
- Schizophrenia
- Being tested
- Cognitive enhancement therapy (CET), Enriched supportive therapy (EST)
- Keywords
- Schizophrenia, Cognition, Enhancement, Randomized
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cognitive enhancement therapy (CET)Behavioural
Using 80 to 100 hours of graduated exercises in computer assisted training, coupled with structured but unrehearsed in vivo social group interactions, CET tries to shift an early developmental reliance on effortful, serial and verbatim cognitive processing to a more gistful, less effortful and spontaneous abstraction of social themes. CET uses attention, memory and problem solving software from three exercises from Ben-Yishay's Orientation Remediation Module (the Attention Reaction Conditioner, Zero Accuracy Conditioner, and Time Estimates) that are graduated in difficulty and designed to enhance vigilance, selective attention, the ability to shift between auditory and visual modalities, and rapid decision-making.
Enriched supportive therapy (EST)Behavioural
EST is the commonly recommended (Spaulding 1992) treatment for control and experimental subjects in psychosocial trials. EST is a two-staged treatment that requires weekly one-hour sessions in Phase 1 and biweekly sessions in Phase 2. Some practice principles (e.g., psychoeducation and relaxation training) are provided during the group exercises for CET patients, but individually for EST patients. No attempt is made to control for hours of contact between EST and CET, since offering three hours of supportive therapy to EST subjects is neither logistically feasible nor faithful to the goals and methods of supportive therapy. Further, neurobiological hypotheses related to treatment specificity would be best tested by clear differences in treatment intensity and content.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Participants will receive cognitive enhancement therapy Receives: Behavioral: Cognitive enhancement therapy (CET) |
| 2 | Placebo comparator | Participants will receive enriched supportive therapy Receives: Behavioral: Enriched supportive therapy (EST) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical, neuropsychological, and functional outcomes
Measured: Measured at Years 1 and 3
Secondary outcomes (1)
Neuroimaging parameters
Measured: Measured at Year 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2005 (estimated)
- Study startAug 2001
- Primary completionAug 2009
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by Beth Israel Deaconess Medical CenterThe 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
- None (open label)
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- Beth Israel Deaconess Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Matcheri S. Keshavan MD, Beth Israel Deaconess Medical Center
- Investigators
- Matcheri S Keshavan, MD, Principal investigator, University of PittsburghGerard E Hogarty, MSW, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00167362
- Sponsor's protocol ID
- R01MH060902
- Other IDs
- R01MH060902, DATR A2-AISZ
- Status last verified
- Jan 2017
- First submitted
- 9 Sep 2005
- Last updated
- 10 Jan 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Hogarty GE. Reinventing evidence-based interventions? Psychiatr Serv. 2005 Sep;56(9):1156; author reply 1156-7. doi: 10.1176/appi.ps.56.9.1156. No abstract available.
PubMed 16148337Hogarty GE, Flesher S, Ulrich R, Carter M, Greenwald D, Pogue-Geile M, Kechavan M, Cooley S, DiBarry AL, Garrett A, Parepally H, Zoretich R. Cognitive enhancement therapy for schizophrenia: effects of a 2-year randomized trial on cognition and behavior. Arch Gen Psychiatry. 2004 Sep;61(9):866-76. doi: 10.1001/archpsyc.61.9.866.
PubMed 15351765Hogarty GE. Medication adherence studies in schizophrenia. Am J Psychiatry. 2004 Mar;161(3):581-2; author reply 582-3. doi: 10.1176/appi.ajp.161.3.581-a. No abstract available.
PubMed 14992994Hogarty GE. Cognitive rehabilitation of schizophrenia. Harv Ment Health Lett. 2000 Aug;17(2):4-6. No abstract available.
PubMed 10927651Hogarty GE, Flesher S. Practice principles of cognitive enhancement therapy for schizophrenia. Schizophr Bull. 1999;25(4):693-708. doi: 10.1093/oxfordjournals.schbul.a033411.
PubMed 10667740Keshavan MS, Hogarty GE. Brain maturational processes and delayed onset in schizophrenia. Dev Psychopathol. 1999 Summer;11(3):525-43. doi: 10.1017/s0954579499002199.
PubMed 10532623Hogarty GE, Ulrich RF. The limitations of antipsychotic medication on schizophrenia relapse and adjustment and the contributions of psychosocial treatment. J Psychiatr Res. 1998 May-Aug;32(3-4):243-50. doi: 10.1016/s0022-3956(97)00013-7.
PubMed 9793877Eack SM, Hogarty GE, Cho RY, Prasad KM, Greenwald DP, Hogarty SS, Keshavan MS. Neuroprotective effects of cognitive enhancement therapy against gray matter loss in early schizophrenia: results from a 2-year randomized controlled trial. Arch Gen Psychiatry. 2010 Jul;67(7):674-82. doi: 10.1001/archgenpsychiatry.2010.63. Epub 2010 May 3.
PubMed 20439824
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rehabilitation, Brain Function and Early Schizophrenia
- ClinicalTrials.gov ID
- NCT00167362
- Acronym / sponsor ID
- R01MH060902
- Conditions
- Schizophrenia
- Keywords
- Schizophrenia, Cognition, Enhancement, Randomized
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 67 participants (actual)
- Lead sponsor
- Beth Israel Deaconess Medical CenterUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Aug 2001
- Primary completion
- Aug 2009 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 14 Sep 2005 (estimated)
- Results
- Not posted in the source record
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 the effectiveness of cognitive enhancement therapy (CET) in treating cognitive abnormalities in people experiencing the early stages of schizophrenia.
Detailed description
In this study, we wish to determine the neurobiological predictors and the relative efficacy of Cognitive Enhancement Therapy (CET) in ameliorating specific cognitive abnormalities presumably mediated by PFC and related brain structures, among younger, early-course schizophrenia patients who potentially have a better prognosis. A series of recent-onset schizophrenic patients, whose psychotic symptoms have successfully been stabilized on an atypical antipsychotic drug for one year following initiation of treatment, will be randomized to CET combined with an enriched supportive therapy (EST) or EST alone, and treated for two years. Subjects will have been assessed on neurobehavioral and clinical indices immediately prior to beginning CET or EST (corresponding with the CNMD 1-year follow-up) and in the proposed study will again be assessed after 1 and 2 years of psychosocial treatment. In a smaller subset of patients, we will also seek to collect preliminary data on the efficacy of CET in reversing the neurobiological alterations in the PFC. The hypotheses of this study are:
- The presence of relatively well preserved PFC structure and function (PFC volume, activation with fMRI, and metabolism as measured by proton MRS) at baseline will predict a better response to CET (Neurobiological Prediction Hypothesis).
- CET combined with "enriched" supportive psychotherapy (EST) will be more effective than EST alone in ameliorating social and non-social cognitive deficits of patients with early schizophrenic illness whose psychotic symptoms have been stabilized on maintenance chemotherapy (The Treatment Efficacy Hypothesis).
- CET will result in additive, positive effects on neurocognitive parameters that were not observed following one year of antipsychotic medication, using a "sequential" treatment design in a subset of patients in whom we have pre-neuroleptic baseline data from CNMD studies (The Treatment Specificity Hypothesis).
Study Design: Subjects will be randomly assigned, once stabilized clinically, to CET plus EST (n = 30) or EST alone (n = 30) and then treated for up to two years. Clinical, neuropsychological, neurological and functional neuroimaging assessments will be administered at baseline and at two annual follow-ups. At the end of CET or EST treatment, subjects will be asked to come back quarterly to meet informally with either their Cognitive Enhancement Therapy clinicians and former group members, or with their Enriched Supportive Therapy clinician. The purpose of these visits is for us to learn more about the successes that patients have had, or about the difficulties that they might have had since leaving the program. Clinician(s) will also share information obtained during this follow-up which might help patient in overcoming these difficulties. At the end of the one-year period post EST or CET treatment, subjects will be assessed on all measures, except for diagnostic, imaging and blood studies.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Behavioral: Cognitive enhancement therapy (CET)Participants will receive cognitive enhancement therapy |
| 2 | Placebo comparator | Behavioral: Enriched supportive therapy (EST)Participants will receive enriched supportive therapy |
Who may qualify
- Ages
- 16 to 51 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- DSM-IV diagnosis of schizophrenia, schizoaffective or schizophreniform disorder at the time of initial assessment
- Pre-treatment illness duration an average of 5 years, not to exceed 8 years
- Stable positive symptoms (e.g., if present do not grossly interfere with behavior such as command hallucinations or delusions)
- Currently maintained and compliant with prescribed antipsychotic medication
- Socially and cognitively disabled, e.g., meet criteria on a Cognitive Style Scale (score greater than or equal to 7), and Social Cognition Disability Scale (score greater than or equal to 12).
Key exclusion criteria (5 listed)
- Alcohol/drug abuse or dependence that has significantly interfered with adjustment in the past two months (e.g., patients currently undergoing D and A treatment must successfully complete their recovery program prior to referral)
- Organic brain syndrome, including HIV illness (due to its effect on CNS function)
- IQ below 80 or language skills below the sixth grade level
- Medical contraindications that preclude an appropriate antipsychotic medication
- Persistent suicidality
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 |
|---|---|---|
| Cognitive enhancement therapy (CET)Using 80 to 100 hours of graduated exercises in computer assisted training, coupled with structured but unrehearsed in vivo social group interactions, CET tries to shift an early developmental reliance on effortful, serial and verbatim cognitive processing to a more gistful, less effortful and spontaneous abstraction of social themes. CET uses attention, memory and problem solving software from three exercises from Ben-Yishay's Orientation Remediation Module (the Attention Reaction Conditioner, Zero Accuracy Conditioner, and Time Estimates) that are graduated in difficulty and designed to enhance vigilance, selective attention, the ability to shift between auditory and visual modalities, and rapid decision-making. | Behavioural | 1 |
| Enriched supportive therapy (EST)EST is the commonly recommended (Spaulding 1992) treatment for control and experimental subjects in psychosocial trials. EST is a two-staged treatment that requires weekly one-hour sessions in Phase 1 and biweekly sessions in Phase 2. Some practice principles (e.g., psychoeducation and relaxation training) are provided during the group exercises for CET patients, but individually for EST patients. No attempt is made to control for hours of contact between EST and CET, since offering three hours of supportive therapy to EST subjects is neither logistically feasible nor faithful to the goals and methods of supportive therapy. Further, neurobiological hypotheses related to treatment specificity would be best tested by clear differences in treatment intensity and content. | Behavioural | 2 |
Primary outcome
Clinical, neuropsychological, and functional outcomes
Time frame: Measured at Years 1 and 3
1 secondary outcome
Neuroimaging parameters
Time frame: Measured at Year 2
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2017.
- Background: PubMed 16148337Hogarty GE. Reinventing evidence-based interventions? Psychiatr Serv. 2005 Sep;56(9):1156; author reply 1156-7. doi: 10.1176/appi.ps.56.9.1156. No abstract available.
- Background: PubMed 15351765Hogarty GE, Flesher S, Ulrich R, Carter M, Greenwald D, Pogue-Geile M, Kechavan M, Cooley S, DiBarry AL, Garrett A, Parepally H, Zoretich R. Cognitive enhancement therapy for schizophrenia: effects of a 2-year randomized trial on cognition and behavior. Arch Gen Psychiatry. 2004 Sep;61(9):866-76. doi: 10.1001/archpsyc.61.9.866.
- Background: PubMed 14992994Hogarty GE. Medication adherence studies in schizophrenia. Am J Psychiatry. 2004 Mar;161(3):581-2; author reply 582-3. doi: 10.1176/appi.ajp.161.3.581-a. No abstract available.
- Background: PubMed 10927651Hogarty GE. Cognitive rehabilitation of schizophrenia. Harv Ment Health Lett. 2000 Aug;17(2):4-6. No abstract available.
- Background: PubMed 10667740Hogarty GE, Flesher S. Practice principles of cognitive enhancement therapy for schizophrenia. Schizophr Bull. 1999;25(4):693-708. doi: 10.1093/oxfordjournals.schbul.a033411.
- Background: PubMed 10532623Keshavan MS, Hogarty GE. Brain maturational processes and delayed onset in schizophrenia. Dev Psychopathol. 1999 Summer;11(3):525-43. doi: 10.1017/s0954579499002199.
- Background: PubMed 9793877Hogarty GE, Ulrich RF. The limitations of antipsychotic medication on schizophrenia relapse and adjustment and the contributions of psychosocial treatment. J Psychiatr Res. 1998 May-Aug;32(3-4):243-50. doi: 10.1016/s0022-3956(97)00013-7.
- Derived from this study: PubMed 20439824Eack SM, Hogarty GE, Cho RY, Prasad KM, Greenwald DP, Hogarty SS, Keshavan MS. Neuroprotective effects of cognitive enhancement therapy against gray matter loss in early schizophrenia: results from a 2-year randomized controlled trial. Arch Gen Psychiatry. 2010 Jul;67(7):674-82. doi: 10.1001/archgenpsychiatry.2010.63. Epub 2010 May 3.
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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.
Matcheri S Keshavan, MD principal investigator
University of Pittsburgh
Gerard E Hogarty, MSW principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cognitive enhancement therapy (CET) and Enriched supportive therapy (EST) in people with Schizophrenia, run by Beth Israel Deaconess Medical Center 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 5 inclusion and 5 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 Jan 2017. 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.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Clinical, neuropsychological, and functional outcomes (time frame: Measured at Years 1 and 3). 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 NCT00167362, which also lists 8 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 Jan 2017.