Memantine Augmentation of Targeted Cognitive Training in Schizophrenia
- Conditions
- SchizophreniaSchizoaffective Disorder
- Interventions
- Drug: Placebo
- Registration Number
- NCT04857983
- Lead Sponsor
- University of California, San Diego
- Brief Summary
Treatment of schizophrenia currently includes antipsychotic medications and cognitive therapies which improve some symptoms, but do not sufficiently restore cognitive functioning or reduce psychosocial disability. We hypothesize that medications that specifically target sensory information processing deficits, rather than psychotic symptoms per se, will significantly enhance the benefits of a sensory-based targeted cognitive training (TCT) intervention in patients with schizophrenia. We will complete a randomized, double-blind clinical trial to: 1) confirm that the drug memantine augments TCT learning; 2) determine whether memantine enhances the clinical benefits from a full 30 session course of TCT vs. TCT plus placebo in antipsychotic- medicated schizophrenia patients, and 3) determine if memantine's enhancement of TCT is most effective in biomarker-defined subgroups of patients.
- Detailed Description
Treatment of schizophrenia (SZ) currently includes antipsychotic medications and cognitive therapies which improve some symptoms, but do not sufficiently restore cognitive functioning or reduce psychosocial disability. We propose and will test a novel "augmentation strategy" for using medications to specifically enhance the benefits of targeted cognitive training (TCT) in schizophrenia. This project tests a rational and empirically supported platform for augmenting the benefits of TCT in antipsychotic medicated SZ patients by adjunctive daily treatment of 20 mg memantine, an FDA approved medication for the treatment of cognitive dysfunction in Alzheimer's Disease. We hypothesize that medications that specifically target sensory information processing deficits, rather than psychotic symptoms per se, will significantly enhance the benefits of a sensory-based targeted cognitive training (TCT) intervention in patients with schizophrenia. We will complete a randomized, double-blind clinical trial to: 1) confirm that the drug memantine augments TCT learning; 2) determine whether memantine enhances the clinical benefits from a full 30 session course of TCT vs. TCT plus placebo in antipsychotic- medicated schizophrenia patients, and 3) determine if memantine's enhancement of TCT is most effective in biomarker-defined subgroups of patients.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 62
- DSM-IV diagnosis of schizophrenia or schizoaffective disorder
- Written informed consent to participate in the study
- Age 18-65
- Absence of dementia or mental retardation
- Urine toxicology negative for recreational drugs
- Fluent and literate in English
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description TCT + PBO Placebo Subjects will be assigned to take placebo and will complete 30 hours of targeted cognitive training in order to assess whether memantine enhances cognitive training performance TCT + MEM Memantine Subjects will be assigned to take memantine and will complete 30 hours of targeted cognitive training in order to assess whether memantine enhances cognitive training performance
- Primary Outcome Measures
Name Time Method Positive & Negative Symptom Scale total (PANSSt) approximately 25 weeks PANSS Total Score is the primary clinical outcome measured at baseline vs. post TCT session 10, 20 and 30 (approximately 13 weeks), and 12 weeks post-TCT. The PANSS total score has a range 30-210, with higher scores indicating worse outcome.
World Health Organization Disability Schedule (WHODAS 2.0) approximately 25 weeks 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 13 weeks), and 12 weeks post-TCT. The World Health Organization Disability Schedule (WHODAS 2.0) has a range 12-60, with higher scores indicating worse outcome.
MATRICS Consensus Cognitive Battery Global Composite T-score (MCCB-C) approximately 25 weeks 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 13 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 Positive & Negative Symptom Scale (PANSS) positive and negative symptom subscales approximately 25 weeks Positive \& Negative Symptom Scale (PANSS) positive and negative symptom subscales measured at baseline vs. post-TCT session 10, 20 and 30 (approximately 13 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.
Individual MATRICS Consensus Cognitive Battery (MCCB) domain T-scores approximately 25 weeks Individual MATRICS Consensus Cognitive Battery (MCCB) domain T-scores measured at baseline vs. post-TCT session 10, 20 and 30 (approximately 13 weeks), and 12 weeks post-TCT. 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 - PSYRATS hallucination subscale approximately 25 weeks Psychotic Symptom Rating Scales (PSYRATS hallucination subscale) measured at baseline vs. post-TCT session 10, 20 and 30 (approximately 13 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 - Young Mania Rating Scale approximately 25 weeks Young Mania Rating Scale total score measured at baseline vs. post-TCT session 10, 20 and 30 (approximately 13 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 - PHQ-9 approximately 25 weeks Patient Health Questionnaire-9 (PHQ-9) total score measured at baseline vs. post-TCT session 10, 20 and 30 (approximately 13 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.
Suicidal Ideation - C-SSRS approximately 25 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.
Treatment satisfaction approximately 13 weeks Treatment satisfaction scale measured at screening and post-TCT session 30 (approximately 13 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 B-403 at UCSD Medical Center)
🇺🇸San Diego, California, United States