SchizophreniaNCT01234454
Atypical Antipsychotic Treatment Effect On Brain Function In Schizophrenia Measured By FMRI
A study testing Risperidone and Olanzapine in people with Schizophrenia, run by University of North Carolina, Chapel Hill at 1 site in United States.
Trial summary
The general aim is to compare the effects of typical and atypical antipsychotic medication on brain structure and function. A parallel group treatment trial will be utilized to compare the effects of the typical antipsychotic thiothixene versus the atypical antipsychotics risperidone (RIS) and olanzapine (OLZ) on… Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Schizophrenia
- What is being tested?
- Risperidone and Olanzapine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2002to Dec 2007
- Phase
- Interventional
- 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 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Inclusion Criteria for Schizophrenia/Schizoaffective Subjects
- Men and women between ages of 18 to 60 inclusive, of any ethnic origin.
- Subjects must be right handed.
- DSM IV criteria for chronic schizophrenia or schizoaffective disorder.
- Good physical health as determined by complete physical examination, laboratory tests, and EKG
- 1. Fifteen individuals, matched to the patient subjects on the basis of age, gender, parental SES, handedness.
Who cannot join
- Exclusion Criteria for Schizophrenia/Schizoaffective Subjects
- Previous poor response or adverse side effects to thiothixene, olanzapine or risperidone.
- Left handedness
- Epilepsy, HIV, or current myeloproliferative disorder
- Current severe major depression.
- Current or past history of Substance Dependence (except caffeine or nicotine)
Show all 14Show fewer
- Criteria for active Substance Abuse within past 30 days
- Learning disability
- Mental Retardation
- Foreign metal objects or implants as determined by MRI safety questionnaires
- If judged unsuitable for the study based on other medical or psychiatric condition according to the PIs best clinical judgment.
- No depot neuroleptic within 60 days before the day of randomization.
- Women who are pregnant or breastfeeding, and/or unwilling to take a pregnancy test.
- 1. History of psychiatric disorder or current medical illness
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Risperidone Effects On Frontal And Temporal Cortical Function In Schizophrenia Patients Undergoing FMRI Cognitive Task Performance
The general aim is to compare the effects of typical and atypical antipsychotic medication on brain structure and function. A parallel group treatment trial will be utilized to compare the effects of the typical antipsychotic thiothixene versus the atypical antipsychotics risperidone (RIS) and olanzapine (OLZ) on brain structure and function in schizophrenia in an effort to determine the neuroanatomic basis for cognitive pathology in schizophrenia and its amelioration by atypical antipsychotic drugs.
Read the detailed description
The general aim of this study was to determine the neuroanatomic basis for cognitive pathology in schizophrenia, as well as the effects of treatment with typical and atypical antipsychotics on clinical symptoms, neurocognition and brain function, as measured with function magnetic resonance imaging. Subjects underwent a randomized parallel group treatment trial that consisted of: a four-week Thiothixene treatment period, followed by randomization, two-weeks cross titration, and six-weeks of double blind treatment with Risperidone (RIS) or Olanzapine (OLZ). Twenty-three patients with schizophrenia or schizoaffective disorder and fifteen healthy control subjects were initially enrolled. Diagnosis was established with the SCID. Subjects were assessed at two time points, at baseline after four weeks of Thiothixene treatment and at follow up, after eight weeks of double-blind atypical antipsychotic treatment. Controls were assessed once. Symptom severity was assessed using the PANSS. Cognitive functions associated with frontal and temporal cortical regions were probed with a neurocognitive testing battery using standardized attention, executive function and working memory tasks. Frontal and temporal cortical function was assessed with fMRI during the performance of visual and auditory oddball tasks. The visual task oddball task consisted of identifying an infrequent square presented within a series of frequent squares. The auditory oddball task consisted of identifying an infrequent pitch-deviant target tone embedded within a series of frequent standard tones. Thirteen patients and eleven controls completed fMRI at baseline and follow-up.
The results indicated that patients treated with the typical neuroleptic Thiothixene showed significantly smaller extents of activations in superior temporal, anterior cingulate and thalamic regions as compared to control subjects during the auditory oddball task. Although treatment with atypical neuroleptics considerably reduced group differences in cortical activation between controls and patients, the current sample size proved to be insufficient to yield statistically significant group by time interactions. The percent signal change data was in the same direction, but proved to be less sensitive to group differences than the extent of activation. The group differences were not pronounced during the visual oddball task, but were in the same direction.
- Conditions
- Schizophrenia
- Being tested
- Risperidone, Olanzapine
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RisperidoneDrug
Also called risperidol, risperidal
6mg/day or highest dose tolerated for 8 weeks, following 4 weeks baseline treatment of Thiothixene
OlanzapineDrug
Also called Zydis, Zyprexa
20mg/day for 8 weeks, following 4 weeks of baseline Thiothixene.
| Study group | Role | What they receive |
|---|---|---|
| Risperidone Treatment Group | Experimental | A two-week cross-titration phase followed randomization when patients started treatment with Risperidone in a double-blind manner and were tapered off Thiothixene. A six-week double blind active treatment period followed. Target dose was 6mg/day or highest dose tolerated. Receives: Drug: Risperidone |
| Olanzapine Treatment Group | Experimental | A two-week cross-titration phase followed randomization when patients started treatment with Olanzapine in a double-blind manner and were tapered off Thiothixene. A six-week double blind active treatment period followed. Target dose 20mg/day (or the highest dose tolerated) for 8 weeks, following 4 weeks of baseline Thiothixene. Receives: Drug: Olanzapine |
| Thiothixene | No intervention | Subjects were first stabilized on open-label Thiothixene for four weeks, target dose 25 mg per day. Patients were then randomized to either Risperidone or Olanzapine treatment for 8 weeks. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neurocognitive Assessment Procedure
Composite score derived from the neurocognitive battery used in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia clinical trial and the Brief Assessment of Cognition in Schizophrenia (BACS).
Measured: Baseline, after four weeks of Thiothixine, then follow-up after 8 weeks
fMRI activation Tasks
During MR imaging subjects performed one visual-auditory target detection task and one auditory oddball task. Subjects completed runs consisting of 160 trials with a total duration of approximately 4 min. During odd numbered runs, subjects performed a visual target detection task. During even numbered runs, subjects performed an auditory target detection task.
Measured: Baseline, after four weeks of Thiothixine, then follow-up after 8 weeks
Secondary outcomes (2)
Performance accuracy on Visual-auditory target detection task
Per fMRI activation tasks. For the visual task, subjects were asked to pay attention to a screen where two types of stimuli were displayed: 1) Standards were squares of varying size and color that comprised ~95% of trials 2) Targets were circles of varying zize and colors that were presented irriegularly on ~5% of trials. The onsets of successive Targets were separated by a minimum of 15 seconds.
Measured: Baseline, after four weeks of Thiothixine, then follow-up after 8 weeks
Performance accuracy on Auditory oddball target detection task
Per fMRI activation tasks. Subjects were asked to pay attention to attend to auditory stimuli presented at a rate of one per 500 msecs for each run. Standards were 500 msec duration 440 Hz pure tones that were presented on ~95% of trials. Frequency-deviant Target tones were 500msec duration 800 Hz pure tones presented irregularly on ~5% of trials. The onsets of successive deviant tones were separated by a minimum of 15 seconds. During both tasks subjects were instructed to press a button whenever a Target was presented. No overt or covert response was required of Standards.
Measured: baseline, after four weeks of Thiothixine, then follow-up after 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2010 (estimated)
- Study startJan 2002
- Primary completionJun 2005
- Study completionDec 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Investigators
- AYSENIL BELGER, Principal investigator, University of North Carolina, Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01234454
- Sponsor's protocol ID
- RIS-USA-242
- Status last verified
- Nov 2010
- First submitted
- 2 Nov 2010
- Last updated
- 3 Apr 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Risperidone Effects On Frontal And Temporal Cortical Function In Schizophrenia Patients Undergoing FMRI Cognitive Task Performance
- ClinicalTrials.gov ID
- NCT01234454
- Acronym / sponsor ID
- RIS-USA-242
- Conditions
- Schizophrenia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Study start
- Jan 2002
- Primary completion
- Jun 2005 (actual)
- Study completion
- Dec 2007 (actual)
- First posted
- 4 Nov 2010 (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.
The general aim is to compare the effects of typical and atypical antipsychotic medication on brain structure and function. A parallel group treatment trial will be utilized to compare the effects of the typical antipsychotic thiothixene versus the atypical antipsychotics risperidone (RIS) and olanzapine (OLZ) on brain structure and function in schizophrenia in an effort to determine the neuroanatomic basis for cognitive pathology in schizophrenia and its amelioration by atypical antipsychotic drugs.
Detailed description
The general aim of this study was to determine the neuroanatomic basis for cognitive pathology in schizophrenia, as well as the effects of treatment with typical and atypical antipsychotics on clinical symptoms, neurocognition and brain function, as measured with function magnetic resonance imaging. Subjects underwent a randomized parallel group treatment trial that consisted of: a four-week Thiothixene treatment period, followed by randomization, two-weeks cross titration, and six-weeks of double blind treatment with Risperidone (RIS) or Olanzapine (OLZ). Twenty-three patients with schizophrenia or schizoaffective disorder and fifteen healthy control subjects were initially enrolled. Diagnosis was established with the SCID. Subjects were assessed at two time points, at baseline after four weeks of Thiothixene treatment and at follow up, after eight weeks of double-blind atypical antipsychotic treatment. Controls were assessed once. Symptom severity was assessed using the PANSS. Cognitive functions associated with frontal and temporal cortical regions were probed with a neurocognitive testing battery using standardized attention, executive function and working memory tasks. Frontal and temporal cortical function was assessed with fMRI during the performance of visual and auditory oddball tasks. The visual task oddball task consisted of identifying an infrequent square presented within a series of frequent squares. The auditory oddball task consisted of identifying an infrequent pitch-deviant target tone embedded within a series of frequent standard tones. Thirteen patients and eleven controls completed fMRI at baseline and follow-up.
The results indicated that patients treated with the typical neuroleptic Thiothixene showed significantly smaller extents of activations in superior temporal, anterior cingulate and thalamic regions as compared to control subjects during the auditory oddball task. Although treatment with atypical neuroleptics considerably reduced group differences in cortical activation between controls and patients, the current sample size proved to be insufficient to yield statistically significant group by time interactions. The percent signal change data was in the same direction, but proved to be less sensitive to group differences than the extent of activation. The group differences were not pronounced during the visual oddball task, but were in the same direction.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Risperidone Treatment Group | Experimental | Drug: RisperidoneA two-week cross-titration phase followed randomization when patients started treatment with Risperidone in a double-blind manner and were tapered off Thiothixene. A six-week double blind active treatment period followed. Target dose was 6mg/day or highest dose tolerated. |
| Olanzapine Treatment Group | Experimental | Drug: OlanzapineA two-week cross-titration phase followed randomization when patients started treatment with Olanzapine in a double-blind manner and were tapered off Thiothixene. A six-week double blind active treatment period followed. Target dose 20mg/day (or the highest dose tolerated) for 8 weeks, following 4 weeks of baseline Thiothixene. |
| Thiothixene | No intervention | –Subjects were first stabilized on open-label Thiothixene for four weeks, target dose 25 mg per day. Patients were then randomized to either Risperidone or Olanzapine treatment for 8 weeks. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Inclusion Criteria for Schizophrenia/Schizoaffective Subjects
- Men and women between ages of 18 to 60 inclusive, of any ethnic origin.
- Subjects must be right handed.
- DSM IV criteria for chronic schizophrenia or schizoaffective disorder.
- Good physical health as determined by complete physical examination, laboratory tests, and EKG
Key exclusion criteria (14 listed)
- Exclusion Criteria for Schizophrenia/Schizoaffective Subjects
- Previous poor response or adverse side effects to thiothixene, olanzapine or risperidone.
- Left handedness
- Epilepsy, HIV, or current myeloproliferative disorder
- Current severe major depression.
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 |
|---|---|---|
| RisperidoneAlso: risperidol, risperidal6mg/day or highest dose tolerated for 8 weeks, following 4 weeks baseline treatment of Thiothixene | Drug | Risperidone Treatment Group |
| OlanzapineAlso: Zydis, Zyprexa20mg/day for 8 weeks, following 4 weeks of baseline Thiothixene. | Drug | Olanzapine Treatment Group |
Primary outcome
Neurocognitive Assessment Procedure
Time frame: Baseline, after four weeks of Thiothixine, then follow-up after 8 weeks
Composite score derived from the neurocognitive battery used in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia clinical trial and the Brief Assessment of Cognition in Schizophrenia (BACS).
fMRI activation Tasks
Time frame: Baseline, after four weeks of Thiothixine, then follow-up after 8 weeks
During MR imaging subjects performed one visual-auditory target detection task and one auditory oddball task. Subjects completed runs consisting of 160 trials with a total duration of approximately 4 min. During odd numbered runs, subjects performed a visual target detection task. During even numbered runs, subjects performed an auditory target detection task.
2 secondary outcomes
Performance accuracy on Visual-auditory target detection task
Time frame: Baseline, after four weeks of Thiothixine, then follow-up after 8 weeks
Performance accuracy on Auditory oddball target detection task
Time frame: baseline, after four weeks of Thiothixine, then follow-up after 8 weeks
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 3 Apr 2015.
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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.
AYSENIL BELGER principal investigator
University of North Carolina, Chapel Hill
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Risperidone and Olanzapine in people with Schizophrenia, run by University of North Carolina, Chapel Hill 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 6 inclusion and 14 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 3 Apr 2015. 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. 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?
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?
Neurocognitive Assessment Procedure (time frame: Baseline, after four weeks of Thiothixine, then follow-up after 8 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 Apr 2015.