Atypical Antipsychotic Treatment Effect On Brain Function In Schizophrenia Measured By FMRI

NCT ID: NCT01234454

Last Updated: 2015-04-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-01-31
• Study Completion Date: 2007-12-31

Brief 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 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.

Conditions

Schizophrenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Risperidone Treatment Group

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.

Group Type: EXPERIMENTAL

Risperidone

Intervention Type: DRUG

6mg/day or highest dose tolerated for 8 weeks, following 4 weeks baseline treatment of Thiothixene

Olanzapine Treatment Group

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.

Group Type: EXPERIMENTAL

Olanzapine

Intervention Type: DRUG

20mg/day for 8 weeks, following 4 weeks of baseline Thiothixene.

Thiothixene

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Risperidone

6mg/day or highest dose tolerated for 8 weeks, following 4 weeks baseline treatment of Thiothixene

Intervention Type: DRUG

Olanzapine

20mg/day for 8 weeks, following 4 weeks of baseline Thiothixene.

Intervention Type: DRUG

Other Intervention Names

risperidol, risperidal; Zydis, Zyprexa

Eligibility Criteria

Inclusion Criteria

1. Men and women between ages of 18 to 60 inclusive, of any ethnic origin.

2. Subjects must be right handed.

3. DSM IV criteria for chronic schizophrenia or schizoaffective disorder.

4. 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.

Exclusion Criteria

1. Previous poor response or adverse side effects to thiothixene, olanzapine or risperidone.

2. Left handedness

3. Epilepsy, HIV, or current myeloproliferative disorder

4. Current severe major depression.

5. Current or past history of Substance Dependence (except caffeine or nicotine)

6. Criteria for active Substance Abuse within past 30 days

7. Learning disability

8. Mental Retardation

9. Foreign metal objects or implants as determined by MRI safety questionnaires

10. If judged unsuitable for the study based on other medical or psychiatric condition according to the PIs best clinical judgment.

11. No depot neuroleptic within 60 days before the day of randomization.

12. Women who are pregnant or breastfeeding, and/or unwilling to take a pregnancy test.

1. History of psychiatric disorder or current medical illness

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of North Carolina, Chapel Hill

OTHER

Sponsor Role: lead

Responsible Party

UNC-Chapel Hill, Department of Psychiatry

Principal Investigators

AYSENIL BELGER

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina, Chapel Hill

Locations

Unc Psychiatry

Chapel Hill, North Carolina, United States

Countries

United States

Other Identifiers

RIS-USA-242

Identifier Type: -

Identifier Source: org_study_id