EPI-MINN: Targeting Cognition and Motivation - National

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to perform a practice-based research project designed to assess whether cognition and motivated behavior in early psychosis can be addressed as key treatment goals within real-world settings by using a 12-week mobile intervention program. Participants who are receiving care at coordinated specialty care (CSC) early psychosis clinics across the United States will be recruited to participate in this study. A qualifying CSC program will provide comprehensive clinical services such as psychotherapy, medication management, psychoeducation, and work or education support. This study will be conducted remotely, and participants can participate at home with their own electronic devices. The aim of this study is to investigate a well-defined 12-week mobile intervention program specifically designed to target cognitive functioning and motivated behavior for individuals with early psychosis. Participants will complete a screening interview which will include diagnosis and symptom ratings, neurocognitive assessment, and self-reports of symptoms, behavior, and functioning. Then participants will be randomized to receive the 12-week mobile intervention, or an active control of treatment as usual. The investigators will test for differences in the clinical trajectories after training, and at two follow up appointments at 6 and 12 months post-training.

Detailed Description
-----------------
Cognitive dysfunction is a core pathophysiological feature of psychosis and one of the strongest predictors of functional outcomes. Several studies indicate that current early intervention programs may not significantly alter long-term clinical outcome, suggesting that critical treatment target(s), beyond symptoms and functional status, are not being addressed. Evidence strongly indicates that, along with cognitive dysfunction, impaired motivation is also a critical target and unmet therapeutic need. The application of effective treatment to improve cognition in early phases of psychosis has a very high likelihood of significantly improving long-term community functioning. The investigators have demonstrated both behavioral gains and improved neural system functioning after neuroscience-informed cognitive training in schizophrenia, in both chronic and early phases of the illness. In young recent-onset individuals (average age of 21 years), the investigators' multi-site double-blind randomized controlled trial showed that 40 hours/ 10 weeks of cognitive training delivered at home over a laptop resulted in significant gains in global cognition, verbal memory, and problem solving compared to a computer games control condition. Cognitive gains were significantly correlated with enhanced thalamic volume and thalamo-cortical connectivity, as well as increased white matter integrity. A meta-analysis of 11 RCTs in early schizophrenia has also indicated the benefit of cognitive remediation approaches. Impaired motivation is also a core feature and very strong predictor of functional outcome in early stages of psychosis. Some studies have shown positive effects in improving motivation immediately after the intervention, but treatments that induce enduring improvements in motivated behavior are scarce. Disturbances in motivated behavior reflect a range of factors, including diminished anticipatory pleasure, difficulty learning from rewarding outcomes, reduction in effort expended to obtain rewarding outcomes, and impairment and disconnection between components of social motivation. This makes it difficult to determine optimal therapeutic approaches. However, some headway is starting to appear in the literature. For instance, social cognition impairments appear to play a specific contributing role to dysfunctions in motivated behavior, and are amenable to intervention. We have found that ratings of motivated behavior improve after social cognition training, and are significantly greater in subjects who performed cognitive training combined with social cognition training, than in those who completed only cognitive training. The investigators have also demonstrated a significant relationship between 6-month social functioning and training-induced improvements in the neural correlates of a self-other reality monitoring task. These data, along with the literature on reward anticipation and on social engagement in psychosis, led this group to work with young clients in a user-centered design process, to develop a mobile app called Personalized Real-time Intervention for Motivational Enhancement (PRIME). The app has been extremely well received by users and published behavioral findings are highly promising. Thus, the investigators will combine a focused course of cognitive plus social cognitive training (delivered remotely) with PRIME, to address the cognitive dysfunction and impaired motivation. Functional recovery lags behind symptom recovery in early intervention programs, is sometimes difficult for individuals to attain, and is closely aligned with cognitive and motivational deficits. How could outcomes for individuals with early psychosis to improved? The results from this study will provide data-driven knowledge on factors that contribute to 2-year treatment response trajectories in early psychosis. The knowledge gained from this clinical trial will deepen understanding of methods to optimize coordinated specialty care to improve clinical trajectories, using a well-defined scalable mobile program that addresses as-of-yet unmet therapeutic needs.

Official Title
-----------------
EPI-MINN: Targeting Cognition and Motivation in Coordinated Specialty Care for Early Psychosis: A National Comparison Study

Conditions
-----------------
Bipolar Disorder, Psychosis, Psychosis Nos/Other, Schizophrenia, Schizo Affective Disorder, Schizoaffective Disorder, Prodromal Schizophrenia, Schizophrenia Spectrum and Other Psychotic Disorders, Schizophreniform Disorders, Major Depression With Psychotic Features, Unspecified Psychosis

Intervention / Treatment
-----------------
* Device: Cognitive and Social Cognitive Training
* Behavioral: Personalized Real-Time Intervention for Motivational Enhancement (PRIME) App
* Other: Early Psychosis Coordinated Specialty Care


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Aged 18-40 (inclusive) Is enrolled in an early psychosis coordinated specialty care clinic In in good general phsycial health (e.g., not acutely ill or experiencing a sever/chronic illness that would impede their ability to complete study activities) Fluent in spoken and written English Estimated IQ at or above 70, as estimated by the Test My Brain matrices task Participants will show overall clinical stability as determined by interview measures. Generally, participants who have not been hospilatlized within the last 30 days and do not have active suicidal ideation will be considered stable. Has access to a smart phone or other mobile device to use the PRIME App Has access to a computer or tablet to complete cognitive training exercises and study assessments Exclusion Criteria: Unable to provide informed consent (i.e., cannot pass UBACC assessment) Participant is under legal commitment to treatment or is under medical guardianship Participated in significant cognitive training programs within the last 3 years Diagnosed with a neurological disorder that may interfere with participation in the study Clinically significant substance abuse that is impeding the participant's ability to participate fully during enrollment, assessment, or training (i.e., is unable to remain sober) Risk of suicidal behavior

Ages Eligible for Study
-----------------
Minimum Age: 15 Years
Maximum Age: 40 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment as Usual<br>Participants will be treated as usual in their early psychosis CSC program and will not complete cognitive training or use the Personalized Real-Time Motivational Enhancement App. | Other: Early Psychosis Coordinated Specialty Care<br>* Participants will continue to engage in treatment as usual at their early psychosis coordinated specialty care clinic. These clinics may follow the NAVIGATE model, as an example.<br>|
| Experimental: Cognitive Training plus Personalized Real-Time Intervention for Motivational Enhancement<br>The Mobile Intervention. 20 hours of training consisting of 10 hours of cognitive training exercises plus 10 hours of social cognitive training exercises will be delivered over the course of 12 weeks. Participants will also engage in the PRIME app on a smart phone and will receive personalized support from a motivation enhancement coach. | Device: Cognitive and Social Cognitive Training<br>* The Cognitive Training Module is designed to improve the speed and accuracy of auditory information processing while engaging working memory and cognitive control under conditions of close attention and reward. The goal is to increase the effectiveness by which salient stimuli engage and drive plastic changes in brain systems that in individuals with psychosis exhibit relatively poor temporal response. The Social Cognition Training Module consists of exercises designed to ameliorate core deficits in social cognition expressed in schizophrenia and Autism Spectrum Disorders. The exercises apply principles of implicit learning to restore the brain's capacity to process and utilize socially-relevant information, and include training to improve affect perception, social cue perception, theory of mind, self-referential style, and emotion labeling and working memory.<br>Behavioral: Personalized Real-Time Intervention for Motivational Enhancement (PRIME) App<br>* The PRIME smartphone-based app is designed to be used for 12 weeks to enhance motivation in people with early psychosis. Participants work towards self-identified goals with the support of the virtual community of age-matched peers, as well as with motivation coaches. Participants discuss their interests and aspirations with each other and with their coach, and the coach sends daily individualized motivational messages. Coaches also provide tailored interventions to enhance motivation, and post daily discussion topics to the PRIME community to encourage interaction between members. Coaches will maintain close communication and feedback on progress with each individual's clinical team.<br>Other: Early Psychosis Coordinated Specialty Care<br>* Participants will continue to engage in treatment as usual at their early psychosis coordinated specialty care clinic. These clinics may follow the NAVIGATE model, as an example.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Test My Brain Scores | Test My Brain is reported as the total score on 4 cognitive domains. The Digit Symbol Matching ranges from 0 -300+, the Verbal Paired Associated ranges from 0 - 25, the Matrix Reasoning ranges from 0 - 35, and the Multiracial Face Emotion Identification Test ranges from 0 - 48. Test My Brain will be assessed at baseline, during pre-training, at 6 months, 12 months, and 18 months. Higher scores indicate higher cognitive function. Performance score is calculated based on accuracy and reaction speed. | 18 months | 
| Change in Dysfunctional Attitudes Scale - Defeatist Beliefs Subscale (DAS-DB) Score | DAS-DB is measured over 14 items with total scores ranging from 14-98, where higher scores indicate greater defeatist beliefs. DAS-DB will be assessed at baseline, 6 months, 12 months, and 18 months. | 18 months | 
| Quality of Life Scale - Abbreviated | The quality of life scale contains 9 items rated from 0 to 6, with higher scores indicating increased functioning/decreased symptom severity. Outcome is reported as 9 separate domain scores. | 18 months | 
| Change in Behavioral Inhibition and Activation Scale (BIS/BAS) - BIS Score | BIS/BAS BIS questionnaire consists of 24 items with total scores ranging from 7-28, where higher scores indicate greater sensitivity to negative aspects of goals. BIS/BAS BIS will be assessed at baseline, 6 months, 12 months, and 18 months. | 18 months | 
| Change in Behavioral Inhibition and Activation Scale (BIS/BAS) - BAS Reward Responsiveness Score | BIS/BAS BAS reward responsiveness questionnaire consists of 24 items with total scores ranging from 5-20, where higher scores indicate greater tendency to be influenced by the possibility of reward when pursuing a goal. BIS/BAS BAS reward responsiveness will be assessed at baseline, 6 months, 12 months, and 18 months. | 18 months | 
| Change in Behavioral Inhibition and Activation Scale (BIS/BAS) - BAS Drive Score | BIS/BAS BAS drive questionnaire consists of 24 items with total scores ranging from 4-16, where higher scores indicate greater persistence in efforts towards obtaining a goal. BIS/BAS BAS drive will be assessed at baseline, 6 months, 12 months, and 18 months. | 18 months | 
| Change in Behavioral Inhibition and Activation Scale (BIS/BAS) - BAS Fun Seeking Score | BIS/BAS BAS fun seeking questionnaire consists of 24 items with total scores ranging from 4-16, where higher scores indicate greater tendency to be influenced by novelty and seeking out new experiences. BIS/BAS BAS fun seeking will be assessed at baseline, 6 months, 12 months, and 18 months. | 18 months | 
| Change in Motivation and Pleasure Scale - Self Report (MAPS-SR) - Social Pleasure Score | MAPS-SR social pleasure questionnaire consists of 15 items with total scores ranging from 0-12, where higher scores indicate increased pathology in this domain. MAPS-SR social pleasure will be assessed at baseline, 6 months, 12 months, and 18 months. | 18 months | 
| Change in Motivation and Pleasure Scale - Self Report (MAPS-SR) - Recreational or Work Pleasure Score | MAPS-SR recreational or work pleasure questionnaire consists of 15 items with total scores ranging from 0-12, where higher scores indicate increased pathology in this domain. MAPS-SR recreational or work pleasure will be assessed at baseline, 6 months, 12 months, and 18 months. | 18 months | 
| Change in Motivation and Pleasure Scale - Self Report (MAPS-SR) - Feelings and Motivations About Close, Caring Relationships Score | MAPS-SR feelings and motivations about close, caring relationships questionnaire consists of 15 items with total scores ranging from 0-24, where higher scores indicate increased pathology in this domain. MAPS-SR feelings and motivations about close, caring relationships will be assessed at baseline, 6 months, 12 months, and 18 months. | 18 months | 
| Change in Motivation and Pleasure Scale - Self Report (MAPS-SR) - Motivation and Effort to Engage in Activities Score | MAPS-SR motivation and effort to engage in activities questionnaire consists of 15 items with total scores ranging from 0-24, where higher scores indicate increased pathology in this domain. MAPS-SR motivation and effort to engage in activities will be assessed at baseline, 6 months, 12 months, and 18 months. | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| COMPASS-10 | The Compass-10 scale consists of 10 items rated on a scale from 0 to 6, with higher scores indicating more severe symptoms of depression and anxiety. Outcome will be reported as 10 separate domain scores. | 18 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Schizophrenia Spectrum Disorders, Remote, Cognitive Training, Motivation Enhancement, First Episode Psychosis