Pharmacologic Augmentation of Targeted Cognitive Training in Schizophrenia

Study Overview
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Brief Summary
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These studies look to conduct efficient pilot testing of a novel intervention strategy for chronic psychotic disorders - Pharmacologic Augmentation of Cognitive Therapy (PACT) - via an experimental medicine approach. Antipsychotics are the major therapeutic tool for chronic psychotic disorders, including schizophrenia, but do not significantly alter their course or real-life impact. Specific cognitive therapies achieve modest symptom reduction and improved function and cognition in psychosis patients, including bottom-up sensory-based targeted cognitive training (TCT). While benefits of TCT are evident at the group level, almost half of all patients demonstrate little or no cognitive gains after 30-40 hours (h) of TCT. For patients and clinicians, the costs and logistical complexities associated with these time- and resource-intensive interventions can be prohibitive. We propose and will test a novel augmentation strategy for using medications to specifically enhance the benefits of TCT in schizophrenia.

Official Title
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Pharmacologic Augmentation of Targeted Cognitive Training in Schizophrenia

Conditions
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Schizophrenia, Schizoaffective Disorder

Intervention / Treatment
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* Drug: AMPH
* Drug: SHAM


Participation Criteria
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Eligibility Criteria
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Inclusion criteria include: DSM-IV diagnosis of schizophrenia or schizoaffective disorder, depressed type Written informed consent to participate in the study Age 18 - 55 Absence of dementia or mental retardation Urine toxicology negative for recreational drugs Fluent and literate in English (needed for completion of WIN and QuickSIN) Exclusion criteria include: Meets DSM-IV criteria for current substance abuse or dependence and has been substance abstinent for less than 30 days A history of traumatic brain injury Auditory or visual impairments severe enough to prevent study participation Under conservatorship (determined by Anasazi) Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: TCT + PBO<br> | Drug: SHAM<br>* Suppressing active psychosis with antipsychotics benefits cognitive interventions for schizophrenia, but it is possible that drugs with pro-cognitive effects will specifically, and perhaps synergistically, augment the clinical benefits of cognitive therapies. A proof of concept for this approach is found in the use of the pro-extinction drugs to selectively enhance the impact of cognitive therapy for anxiety disorders. In this proof of concept, a learning-based therapy is paired with a medication that enhances a brain mechanism (extinction) that is both 1) critical to that form of learning, and 2) known to be deficient in some anxiety disorders.<br>|
| Active Comparator: TCT + AMPH<br> | Drug: AMPH<br>* Suppressing active psychosis with antipsychotics benefits cognitive interventions for schizophrenia, but it is possible that drugs with pro-cognitive effects will specifically, and perhaps synergistically, augment the clinical benefits of cognitive therapies. A proof of concept for this approach is found in the use of the pro-extinction drugs to selectively enhance the impact of cognitive therapy for anxiety disorders. In this proof of concept, a learning-based therapy is paired with a medication that enhances a brain mechanism (extinction) that is both 1) critical to that form of learning, and 2) known to be deficient in some anxiety disorders.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline TCT weekly for 30 weeks, plus 2 post session tests | Sound Sweeps | screening session (week 1) followed by weekly sessions for 10 weeks, 3 times per week (weeks 2-  12), and 2 post session tests after week 12 and after week 22 |