Pharmacologic Augmentation of Targeted Cognitive Training in Schizophrenia
- Conditions
- SchizophreniaSchizoaffective Disorder
- Interventions
- Drug: Placebo
- Registration Number
- NCT04414930
- Lead Sponsor
- University of California, San Diego
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 28
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Placebo Placebo 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 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.
- Primary Outcome Measures
Name Time Method Primary Clinical Outcome approximately 22 weeks Positive \& Negative Symptom Scale total (PANSSt) PANSS Total Score is the primary clinical outcome measured at baseline vs. post-TCT session 10, 20 and 30 (approximately 10 weeks), and 12 weeks post-TCT. The PANSS total score has a range 30-210, with higher scores indicating worse outcome.
Primary Functional Outcome approximately 22 weeks Primary World Health Organization Disability Schedule (WHODAS 2.0) Function will be assessed via the World Health Organization Disability Schedule 2.0 (WHODAS 2.0) at baseline vs. post-TCT session 10, 20 and 30 (approximately 10 weeks), and 12 weeks post-TCT. The WHODAS 2.0 has a range 12-60, with higher scores indicating worse outcome.
Primary Neurocognitive Outcome approximately 22 weeks MATRICS Consensus Cognitive Battery Global Composite T-score (MCCB-C) The MCCB Global Composite T-score (MCCB-C) is the primary neurocognitive outcome measured at baseline vs. post-TCT session 10, 20 and 30 (approximately 10 weeks), and 12 weeks post-TCT. The MATRICS Consensus Cognitive Battery (MCCB) composite T-score has no minimum or maximum score because it uses T-scores, which are standardized based on a community sample. A normal range MCCB composite T-score is between 40 and 60 and higher scores indicate better neurocognitive outcome.
- Secondary Outcome Measures
Name Time Method Secondary Clinical Outcome Measures approximately 22 weeks Positive \& Negative Symptom Scale (PANSS) positive and negative symptom subscales measured at baseline vs. post-TCT session 10, 20 and 30 (approximately 10 weeks), and 12 weeks post-TCT. The PANSS is composed of 3 subscales: Positive Scale, Negative Scale, and General Psychopathology Scale. Each subscale is rated with 1 to 7 points ranging from absent to extreme. The range for the Positive and Negative Scales is 7-49, and the range for the General Psychopathology Scale is 16-112 and higher scores indicate worse outcome.
Secondary Neurocognitive Outcome Measures approximately 22 weeks The MATRICS Consensus Cognitive Battery (MCCB) individual domain T-scores measured at baseline vs. post-TCT session10, 20 and 30 (approximately 10 weeks), and 12 weeks post-TCT are the secondary neurocognitive outcomes. The MCCB domain t-scores have no minimum or maximum score. They are provided as age- and gender-corrected T-scores for seven cognitive domains, with a normative mean of 50 and a standard deviation of 10 with higher scores indicating better neurocognitive outcome.
Psychotic Symptoms approximately 22 weeks Psychotic Symptom Rating Scales (PSYRATS hallucination subscale) assesses auditory hallucinations measured at baseline vs. post-TCT session 10, 20 and 30 (approximately 10 weeks), and 12 weeks post-TCT. The PSYRATS auditory hallucinations subscale (AHS) consisting of 11 items, with each item being rated from 0 (absent) to 4 (severe), range 0-44, with higher scores indicating more severe auditory hallucinations or worse outcome.
Manic Symptoms approximately 22 weeks Young Mania Rating Scale total score measured at baseline vs. post-TCT session 10, 20 and 30 (approximately 10 weeks), and 12 weeks post-TCT. The range for the YMRS total score is 0-60, with higher scores indicating more severe manic symptoms or worse outcome.
Current Depressive Symptoms approximately 22 weeks Patient Health Questionnaire-9 (PHQ-9) total score measured at baseline vs. post-TCT session 10, 20 and 30 (approximately 10 weeks), and 12 weeks post-TCT. The PHQ-9 has a range from 0 to 27 with higher scores indicating more severe depression or worse outcome.
Abnormal Involuntary Movements approximately 22 weeks Abnormal Involuntary Movement Scale total score measured at baseline vs. post-TCT session 10, 20 and 30 (approximately 10 weeks), and 12 weeks post-TCT. The AIMS has a range of 0 to 28 with higher scores indicating more severe abnormal involuntary movements or worse outcome.
Suicidal Ideation approximately 22 weeks Columbia Suicide Severity Rating Scale (C-SSRS) total score measured weekly throughout the study. The C-SSRS sum ranges from 2 to 25, with the higher number indicating greater suicidal ideation or worse outcome.
Amphetamine Withdrawal Symptoms approximately 22 weeks AMPH Cessation Symptom Assessment ratings at the end of the study post-12 week. The AMPH Cessation Symptom Assessment total score range is 0-64, with higher total score reflecting more severe withdrawal symptoms or worse outcome.
Treatment satisfaction approximately 22 weeks Treatment satisfaction scale measured at screening and post-TCT session 30 (approximately 10 weeks).
The Treatment satisfaction scale ranges from 0 to 100 and higher scores indicate greater satisfaction or better outcome.
Trial Locations
- Locations (1)
Clinical Teaching Facility (CTF-B102) at UCSD Medical Center
🇺🇸San Diego, California, United States