Ignite Creation Date:
2024-05-05 @ 5:17 PM
Last Modification Date:
2024-10-26 @ 9:30 AM
Study NCT ID:
NCT00420498
Status:
COMPLETED
Last Update Posted:
2007-12-12
First Post:
2007-01-09
Brief Title:
Effects of Atomoxetine on Cognitive Function in Schizophrenia
Sponsor:
Yale University
Organization:
Yale University
Study Overview
Official Title:
Effects of Atomoxetine on Cognitive Function in Schizophrenia
Status:
COMPLETED
Status Verified Date:
2007-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study is to examine the effects of atomoxetine Strattera on prefrontal cognitive functioning in persons with schizophrenia Secondarily the effects of atomoxetine on positive and negative symptoms and on cigarette smoking consumption in persons with schizophrenia will be examined
Detailed Description:
Schizophrenia occurs in approximately 1 of the general population Hallmark symptoms of schizophrenia include positive and negative symptoms as well as deficits in various aspects of cognitive function with particular reference to neuropsychological tasks related to the prefrontal cortex PFC A leading theory with respect to these deficits in prefrontal cortical functioning is that there is dysregulation with overall hypofunction of mesocortical dopamine DA projections from the VTA to the prefrontal cortex PFC in persons with schizophrenia thus diminishing abilities on tasks mediated by these cortical areas 1 Further it is thought that the high rates of smoking in schizophrenia 58-88 as compared to a non-psychiatric population 25 may be due in part to the tendency of schizophrenic patients to remediate these neurocognitive deficits by cigarette smoking as nicotine has been shown to improve selected cognitive deficits in persons with this illness 2-4 and in fact such cognitive deficits may be a vulnerability factor predisposing these patients to initiate and maintain smoking 5
Atomoxetine Strattera which has efficacy in treating children and adults with Attention Deficit Hyperactivity Disorder ADHD It increases extracellular levels of both NE and DA in the PFC by blocking the NE transporter NET where it has been shown that DA is predominately taken up non-selectively by NET 6 In contrast atomoxetine was not found to increase extracellular DA in subcortical areas 6 It can be theorized that atomoxetine may selectively increase DA in the PFC versus subcortical areas by inhibition of NETs in the PFC Accordingly since persons with schizophrenia are thought to have a deficit of DA in the PFC and excessive subcortical DA function a NET inhibitor such as atomoxetine may increase DA-dependent PFC-mediated neurocognitive functioning and reduce negative symptoms associated with this disorder without worsening positive symptoms of schizophrenia Atomoxetine has been shown to be safe and effective for ADHD treatment in both children and adults Eiland 2004 Little is known about Atomoxetines effects in treating other psychiatric disorders however it has been hypothesized that this medication may have efficacy for cognitive remediation in the schizophrenic population Friedman 2004
In order to more fully understand the effects of this medication a double-blind placebo-controlled clinical trial is proposed in which sixty 60 participants with schizophrenia who are cigarette smokers would be randomized in a double-blind manner to one of three doses of atomoxetine 00 mgday n20 400 mgday n20 or 800 mgday n20 Doses were chosen in accordance with the FDA suggested dosing including a schedule of initiation starting with 400mgday and a target recommended dose of 800mgday which may be reached within a three day period The highest recommended dose is 100 mgday These doses were ultimately selected for this study because they are doses that are believed to be well-tolerated by patients doses that may be achieved within the two-week period of this study and two doses that fit with our intention to study the dose-dependent effects of this medication Safety and effectiveness for these doses has been determined for patients 18 years of age and older with ADD the population that has been studied using Atomoxetine Should we discover that our patients with schizophrenia do not tolerate these doses well through extensive monitoring of their physiological and clinical symptoms or that the maximum dose of 800 mgday cannot be reached during this time period smaller doses will be considered and the appropriate amendments will be submitted
Participants would be assessed across three cognitive testing sessions over a two-week period including baseline assessments Day 1 prior to medication administration on Day 8 after one week of medication and again on Day 15 after two weeks of medication No data currently exists in the literature regarding specific improvements in neurocognitive performance in schizophrenia with atomoxetine although it has been hypothesized that this medication may be specifically helpful in schizophrenia Therefore we believe this will be one of the first studies of its kind We hypothesize that atomoxetine will dose-dependently improve deficits in PFC-related cognitive performance in persons with schizophrenia We secondarily hypothesize that schizophrenic smokers will demonstrate a reduction in negative symptoms and daily cigarette consumption with atomoxetine as compared to placebo
Atomoxetine Strattera which has efficacy in treating children and adults with Attention Deficit Hyperactivity Disorder ADHD It increases extracellular levels of both NE and DA in the PFC by blocking the NE transporter NET where it has been shown that DA is predominately taken up non-selectively by NET 6 In contrast atomoxetine was not found to increase extracellular DA in subcortical areas 6 It can be theorized that atomoxetine may selectively increase DA in the PFC versus subcortical areas by inhibition of NETs in the PFC Accordingly since persons with schizophrenia are thought to have a deficit of DA in the PFC and excessive subcortical DA function a NET inhibitor such as atomoxetine may increase DA-dependent PFC-mediated neurocognitive functioning and reduce negative symptoms associated with this disorder without worsening positive symptoms of schizophrenia Atomoxetine has been shown to be safe and effective for ADHD treatment in both children and adults Eiland 2004 Little is known about Atomoxetines effects in treating other psychiatric disorders however it has been hypothesized that this medication may have efficacy for cognitive remediation in the schizophrenic population Friedman 2004
In order to more fully understand the effects of this medication a double-blind placebo-controlled clinical trial is proposed in which sixty 60 participants with schizophrenia who are cigarette smokers would be randomized in a double-blind manner to one of three doses of atomoxetine 00 mgday n20 400 mgday n20 or 800 mgday n20 Doses were chosen in accordance with the FDA suggested dosing including a schedule of initiation starting with 400mgday and a target recommended dose of 800mgday which may be reached within a three day period The highest recommended dose is 100 mgday These doses were ultimately selected for this study because they are doses that are believed to be well-tolerated by patients doses that may be achieved within the two-week period of this study and two doses that fit with our intention to study the dose-dependent effects of this medication Safety and effectiveness for these doses has been determined for patients 18 years of age and older with ADD the population that has been studied using Atomoxetine Should we discover that our patients with schizophrenia do not tolerate these doses well through extensive monitoring of their physiological and clinical symptoms or that the maximum dose of 800 mgday cannot be reached during this time period smaller doses will be considered and the appropriate amendments will be submitted
Participants would be assessed across three cognitive testing sessions over a two-week period including baseline assessments Day 1 prior to medication administration on Day 8 after one week of medication and again on Day 15 after two weeks of medication No data currently exists in the literature regarding specific improvements in neurocognitive performance in schizophrenia with atomoxetine although it has been hypothesized that this medication may be specifically helpful in schizophrenia Therefore we believe this will be one of the first studies of its kind We hypothesize that atomoxetine will dose-dependently improve deficits in PFC-related cognitive performance in persons with schizophrenia We secondarily hypothesize that schizophrenic smokers will demonstrate a reduction in negative symptoms and daily cigarette consumption with atomoxetine as compared to placebo
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NARSAD | None | None | None |