Pilot Study of Atomoxetine To Enhance COgnition In Patients With Schizophrenia

Sponsor

Research Foundation for Mental Hygiene, Inc. (Other)

Overall Status

Completed

CT.gov ID

NCT00488163

Collaborator

Eli Lilly and Company (Industry)

Enrollment

Locations

Arms

28.9

Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Relationships between altered prefrontal cortical dopamine, norepinephrine and some cognitive impairments of schizophrenia supports and approach for pharmacological remediation of cognitive symptoms through manipulations of prefrontal cortical dopamine and norepinephrine. Atomoxetine, a selective norepinephrine re-uptake inhibitor, produces a widespread increase in brain norepinephrine and a secondary and selective increase in prefrontal dopamine. Given this, we are evaluating atomoxetine's cognitive effects in a pilot placebo controlled trial in patients with schizophrenia. Moreover, an fMRI investigation was undertaken to assess the neural mechanisms underlying the cognitive effects of atomoxetine.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: Atomoxetine	Phase 4

Detailed Description

Participants carrying a diagnosis of schizophrenia and receiving treatment with one of the following antipsychotic medications are eleigible for participation: risperidone, olanzapine, quetiapine, aripirazole. Following consent, participants will be observed for 4 weeks to ensure stability of their symptoms. Following this, there will be baseline assessments of symptom severity, cognitive ability, functional ability and an fMRI scan. Following this, participants will be randomly assigned to receive treatment with 40 mg of atomoxetine or placebo daily during a double-blind parallel designed four week treatment period, following which the dose of atomoxetine will be increased to 40 mg twice day (or matching placebo) for an additional 4 weeks. The cognitive assessment battery and MRI will be repeated following 8 weeks of treatment.

Study Design

Study Type:

Interventional

Actual Enrollment :

20 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Pilot Study of Atomoxetine To Enhance COgnition In Patients With Schizophrenia

Study Start Date :

Jan 1, 2005

Actual Primary Completion Date :

Apr 1, 2007

Actual Study Completion Date :

Jun 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Atomoxetine Atomoxetine 40 mg compounded into capsules.	Drug: Atomoxetine Dose escalation from 40 mg to 50 mg of Atomoxetine active treatment. Other Names: Strattera®
Placebo Comparator: Placebo Inactive matching compounding of placebo capsules	Drug: Atomoxetine Dose escalation from 40 mg to 50 mg of Atomoxetine active treatment. Other Names: Strattera®

Arm

Intervention/Treatment

Active Comparator: Atomoxetine

Atomoxetine 40 mg compounded into capsules.

Drug: Atomoxetine

Dose escalation from 40 mg to 50 mg of Atomoxetine active treatment.

Other Names:

Strattera®

Placebo Comparator: Placebo

Inactive matching compounding of placebo capsules

Drug: Atomoxetine

Dose escalation from 40 mg to 50 mg of Atomoxetine active treatment.

Other Names:

Strattera®

Outcome Measures

Primary Outcome Measures

Composite score on the Brief Assessment of Cognition in Schizophrenia [8 weeks]
Cognitive performance as measured by the BACS

Secondary Outcome Measures

Brain activation measured by functional magnetic resonance imaging [8 weeks]
Differences between changes in brain oxygenation level dependent imaging measures between placebo and Atomoxetine

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Subjects will be males and females between the ages of 18 and 65
In good general medical health
For patient subjects, a DSM-IV diagnosis of schizophrenia, any subtype
Currently in remission or with stable, unchanging residual symptoms
Receiving treatment with olanzapine, aripiprazole, risperidone, or quetiapine as their antipsychotic medication at a stable dose for a minimum of eight weeks.
Able to complete neurocognitive tests
Able to give informed consent. All subjects will be required to have at least an 8th grade reading level and/or a full-scale IQ of at least 85 as assessed by the Wide Range Achievement Test (WRAT).

Exclusion Criteria:

Recent history (within previous year) of serious suicide, homicide, or physical violence, or current suicidal or homicidal thoughts
Any axis I DSM-IV diagnosis in addition to schizophrenia or schizoaffective disorder except substance abuse in remission
History of severe head trauma, neurological disorder, or medical illness which may contribute to the subjects' psychiatric symptoms or cognitive impairment
Medical illness which requires taking any medication that has CNS activity which is known to impair cognition.
Untreated or unstable hypertension.
Coronary artery disease.
Receiving concomitant anticholinergic drugs, antidepressants or mood stabilizers. If patient subjects are receiving benzodiazepines, they must be short or intermediate acting (e.g. alprazolam, lorazepam) and must be held 48 hours prior to cognitive testing
Unable to give informed consent
History of developmental disorder or less than an eighth