Pharmacologic Augmentation of Targeted Cognitive Training in Schizophrenia

NCT ID: NCT04414930

Last Updated: 2025-12-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-09
• Study Completion Date: 2024-12-30

Brief Summary

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.

Detailed Description

Subjects who meet criteria for study entry come to UCSD where consenting and a comprehensive screening and diagnostic assessment including a Mini-International Neuropsychiatric Interview are conducted. After initial screening, subjects return twice, approximately 7 days apart, for biomarker assessment after challenge with placebo (PBO) (Test 1) or amphetamine 5 mg po (AMPH) (Test 2). Subjects then enter the "treatment phase", completing up to 30 one-hour targeted cognitive training (TCT) sessions. Subjects are randomized to one of 2 groups: "AMPH Group" receive AMPH (5 mg po) 1h before each TCT session; "PBO Group" receive PBO dosed identically to AMPH. Pill identity (AMPH vs. PBO) is blind to subjects and staff.

TCT sessions are scheduled approximately 3 times each week for 10 weeks. TCT consists of 7 computerized exercises delivered on standardized laptops and headphones. Collectively, these exercises target learning mechanisms involving auditory perception and processing speed (Sound Sweeps, Fine Tuning) and auditory memory (Syllable Stacks, Memory Grid, To-Do List Training, Rhythm Recall, Hear-Hear). Training is structured into blocks that deliver stimulus sets with varying temporal and psychophysical parameters to allow continuous learning and improvement. Blocks consist of 10-35 adaptive trials where the subject's progression depends on their performance. Exercises apply an n-up/m-down algorithm to responses to estimate psychophysical thresholds while ensuring that participants remain engaged and challenged at an appropriate level (~80% accuracy) as their abilities improve.

Clinical and functional outcome measures are acquired at "baseline", and 1-2 days after completion of 10, 20 and 30 TCT sessions and 12 weeks post-training. Urine toxicology screens and Columbia Suicide Severity Rating Scales are performed at least weekly, prior to a TCT session. A treatment satisfaction scale (100 mm line) rates expectations at the start of the study and actual experience of treatment in three areas: "satisfaction", "hard work" and "worthwhile." Subjects from both groups return to UCSD 12 weeks after the TCT has ended, and outcome measures are reassessed to test the "durability" of benefits.

Conditions

Schizophrenia; Schizoaffective Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo

Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive placebo po 1 hour prior to each training.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive placebo po 1 hour prior to each training.

Active Drug

Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive amphetamine 5 mg po 1 hour prior to each training.

Group Type: ACTIVE_COMPARATOR

d-amphetamine

Intervention Type: DRUG

Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive amphetamine 5 mg po 1 hour prior to each training.

Interventions

d-amphetamine

Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive amphetamine 5 mg po 1 hour prior to each training.

Intervention Type: DRUG

Placebo

Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive placebo po 1 hour prior to each training.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of California, San Diego

OTHER

Sponsor Role: lead

Responsible Party

Neal R. Swerdlow, M.D., Ph.D.

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Neal R Serdlow, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

UC San Diego

Locations

Clinical Teaching Facility (CTF-B102) at UCSD Medical Center

San Diego, California, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

R33MH123603-01

Identifier Type: NIH

Identifier Source: org_study_id

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