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

NCT01234454 | Completed DMC

• 1 other identifier: RIS-USA-242
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

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.

Conditions

Schizophrenia

Outcome Measures

Primary Outcomes (2)

• 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).

  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.

  Baseline, after four weeks of Thiothixine, then follow-up after 8 weeks

Secondary Outcomes (2)

• Performance accuracy on Visual-auditory target detection task

  Baseline, after four weeks of Thiothixine, then follow-up after 8 weeks

• Performance accuracy on Auditory oddball target detection task

  baseline, after four weeks of Thiothixine, then follow-up after 8 weeks

Study Arms (3)

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.

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.

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.

Interventions

Risperidone DRUG

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

Also known as: risperidol, risperidal

Risperidone Treatment Group

Olanzapine DRUG

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

Also known as: Zydis, Zyprexa

Olanzapine Treatment Group

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• \. Fifteen individuals, matched to the patient subjects on the basis of age, gender, parental SES, handedness.

You may not qualify if:

• 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)
• 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.
• \. History of psychiatric disorder or current medical illness

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead

Study Sites (1)

Unc Psychiatry

Chapel Hill, North Carolina, 27599, United States

Location

MeSH Terms

Conditions

Schizophrenia

Interventions

Risperidone; Olanzapine

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• AYSENIL BELGER

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: November 2, 2010
• First Posted: November 4, 2010
• Study Start: January 1, 2002
• Primary Completion: June 1, 2005
• Study Completion: December 1, 2007
• Last Updated: April 3, 2015

Record last verified: 2010-11

Locations

US (1)