Schizoaffective Disorder, Schizophrenia
Conditions
Keywords
schizophrenia, cognitive training, EEG
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.
Interventions
DRUGMemantine
Subjects will be assigned to take memantine or placebo and will complete 30 hours of targeted cognitive training in order to assess whether memantine enhances cognitive training performance
DRUGPlacebo
Subjects will be assigned to take memantine or placebo and will complete 30 hours of targeted cognitive training in order to assess whether memantine enhances cognitive training performance
Sponsors
University of California, San Diego
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Subjects will be randomized to TCT and memantine or TCT and placebo. The research will be provided with a randomization scheme to follow and will dispense the pills identified only by a code.
Intervention model description
Subjects will be randomized to targeted cognitive training (TCT) and memantine (MEM) or targeted cognitive training (TCT) and placebo (PBO)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* 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
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Positive & Negative Symptom Scale Total (PANSSt) | Baseline (at study enrollment), post-10 TCT sessions (approximately week 10), post-20 TCT sessions (approximately week 13) and post-30 TCT sessions (approximately week 16). | PANSS Total Score is the primary clinical outcome measured at baseline vs. post TCT session 10, 20 and 30 (approximately 16 weeks). The PANSS total score has a range 30-210, with higher scores indicating worse outcome. |
| World Health Organization Disability Schedule (WHODAS 2.0) | Baseline (at study enrollment), post-10 TCT sessions (approximately week 10), post-20 TCT sessions (approximately week 13) and post-30 TCT sessions (approximately week 16). | 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 16 weeks). 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) | Baseline (at study enrollment), post-10 TCT sessions (approximately week 10), post-20 TCT sessions (approximately week 13) and post-30 TCT sessions (approximately week 16). | 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 16 weeks). The MATRICS Consensus Cognitive Battery (MCCB) composite T-score has no minimum or maximum score because it uses T-scores (e.g., 50 indicates the population mean with a standard deviation of 10), 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
| Measure | Time frame | Description |
|---|---|---|
| Positive & Negative Symptom Scale (PANSS) - Positive Symptom Subscale | Baseline (at study enrollment), post-10 TCT sessions (approximately week 10), post-20 TCT sessions (approximately week 13) and post-30 TCT sessions (approximately week 16). | Positive \& Negative Symptom Scale (PANSS) positive symptom subscale measured at baseline vs. post-TCT session 10, 20 and 30 (approximately 16 weeks). The PANSS positive symptom subscale is rated from 1 to 7 points ranging from absent to extreme. The range for the Positive Symptom subscale is 7-49 and higher scores indicate worse outcome. |
| Positive & Negative Symptom Scale (PANSS) - Negative Symptom Subscale | Baseline (at study enrollment), post-10 TCT sessions (approximately week 10), post-20 TCT sessions (approximately week 13) and post-30 TCT sessions (approximately week 16). | Positive \& Negative Symptom Scale (PANSS) negative symptom subscale measured at baseline vs. post-TCT session 10, 20 and 30 (approximately 16 weeks). The PANSS negative symptom subscale is rated from 1 to 7 points ranging from absent to extreme. The range for the negative symptom subscale is 7-49 and higher scores indicate worse outcome. |
| Psychotic Symptoms - PSYRATS Hallucination Subscale | Baseline (at study enrollment), post-10 TCT sessions (approximately week 10), post-20 TCT sessions (approximately week 13) and post-30 TCT sessions (approximately week 16). | Psychotic Symptom Rating Scales (PSYRATS hallucination subscale) measured at baseline vs. post-TCT session 10, 20 and 30 (approximately 16 weeks). 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 | Baseline (at study enrollment), post-10 TCT sessions (approximately week 10), post-20 TCT sessions (approximately week 13) and post-30 TCT sessions (approximately week 16). | Young Mania Rating Scale total score measured at baseline vs. post-TCT session 10, 20 and 30 (approximately 16 weeks). 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 | Baseline (at study enrollment), post-10 TCT sessions (approximately week 10), post-20 TCT sessions (approximately week 13) and post-30 TCT sessions (approximately week 16). | Patient Health Questionnaire-9 (PHQ-9) total score measured at baseline vs. post-TCT session 10, 20 and 30 (approximately 16 weeks). The PHQ-9 has a range from 0 to 27 with higher scores indicating more severe depression or worse outcome. |
Countries
United States
Participant flow
Recruitment details
Antipsychotic-medicated outpatients with a primary diagnosis of SZ or schizoaffective disorder (depressed type) ages 18-65 were recruited from the San Diego community between 7/6/2021 and 11/15/2023. Of the 62 consented/enrolled participants, 42 met inclusion criteria and were randomized to treatment, however 2 dropped out prior to initiation of treatment. Therefore 40 subjects participated in the trial.
Pre-assignment details
A total of 62 participants were enrolled but 15 were excluded for not meeting inclusion criteria and 5 withdrew from the study. Two withdrew before initiation of treatment; therefore 40 participants were included. 17 were randomized to placebo and 23 were randomized to memantine.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 48.3 years STANDARD_DEVIATION 12.07 |
| Duration of illness | 20.7 years STANDARD_DEVIATION 11.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants |
| Race (NIH/OMB) More than one race | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 13 Participants |
| Region of Enrollment United States | 17 Participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 23 |
| other Total, other adverse events | 11 / 17 | 10 / 23 |
| serious Total, serious adverse events | 0 / 17 | 0 / 23 |
Outcome results
None listed