Pharmacologic Augmentation of Targeted Cognitive Training in Schizophrenia

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.

Study Overview

• Status: Recruiting
• Conditions: Schizophrenia; Schizoaffective Disorder
• Intervention / Treatment: Drug: SHAM; Drug: AMPH

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jo Benrubi, B.A.; Phone Number: 6195432314; Email: eyeblinkstudy@ucsd.edu

Study Locations

• United States
  • California
    • San Diego, California, United States, 92103
      • Recruiting
      • Clinical Teaching Facility (CTF-B102) at UCSD Medical Center
      • Contact: Jo Talledo Benrubi, B.A.; Phone Number: 619-543-3093; Email: atalledo@ucsd.edu
      • Principal Investigator: Neal R. Swerdlow, M.D., Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: TCT + PBO	Drug: SHAM; 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.
Active Comparator: TCT + AMPH	Drug: AMPH; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of California, San Diego
• Investigators: Principal Investigator: Neal R Serdlow, M.D., Ph.D., UC San Diego

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2020
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): July 1, 2024

Study Registration Dates

• First Submitted: May 22, 2020
• First Submitted That Met QC Criteria: May 29, 2020
• First Posted (Actual): June 4, 2020

Study Record Updates

• Last Update Posted (Actual): July 5, 2023
• Last Update Submitted That Met QC Criteria: June 30, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Psychotic Disorders
• Other Study ID Numbers: R33MH123603-01 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No