Clinical trial NCT05112432: EPI-MINN: Targeting Cognition and Motivation
Official title: EPI-MINN: Targeting Cognition and Motivation in Coordinated Specialty Care for Early Psychosis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Psychosis
Keywords: Cognitive Training
Motivation Enhancement
First Episode Psychosis
Schizophrenia Spectrum Disorders
Lead sponsor: University of Minnesota
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2021-11-08
Enrollment: 400
Sex: ALL
Minimum age (years): 15
Maximum age (years): 40
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 enrolled in a chart review study of measurement-based care will be recruited to participate in this study. In the measurement-based care study, participants are enrolled in coordinated specialty care programs for early psychosis that provide comprehensive clinical services such as psychotherapy, medication management, psychoeducation, work or education support, and measurement-based care. Participants will complete a set of well-defined measures every 6 months that assess symptoms, functioning, cognition and motivation as standard of care. The current study will utilize the data acquired in the measurement-based care study.

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. The investigators will test for differences in the clinical trajectories over 18 months in those who receive the intervention vs. those who do not.

This study will be conducted jointly with a sister protocol under a separate NCT listing. This iteration will be conducted locally within the EPI-MINN Network, while the other project will be conducted on a national scale.

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 the EPI-MINN: Measurement-Based Care study will provide data-driven knowledge on factors that contribute to 2-year treatment response trajectories in early psychosis. This knowledge will be combined with insights from the investigators' current study to 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.

Eligibility criteria: Inclusion Criteria:

* Enrolled in EPI-MINN: Measurement Based Care protocol, STUDY00009334
* Good general health (i.e. not acutely ill or experiencing a severe/chronic illness that would impede their ability to complete study activities. This determination shall be, if necessary, made at the discretion of the PIs)
* Estimated IQ at or above 70, as estimated by the Penn CNP Matrix Reasoning Test
* Achieved clinical stability, defined as outpatient status for at least one month prior to study participation and clinically stable doses of psychiatric medication (by PI discretion) for at least one month prior to study participation (including no medication)
* Has access to a smartphone or other mobile device to use the PRIME app

Exclusion Criteria:

* Under legal commitment to treatment or is under medical guardianship, and there is no provision in the guardianship order or a court order to allow the guardian to consent to participation in research
* Participated in significant cognitive training programs within the last three years
* Diagnosed with a neurological disorder (Autism Spectrum Disorder is allowed)
* Clinically significant substance abuse that is impeding the participant's abulity to participate fully during recruitment, enrollment, assessment, or training, (is unable to remain sober for assessments and training)
* Risk of suicidal behavior, as indicated by the clinicall obtained C-SSRS or clinician judgement. Risk of suicidal behavior is defined as:

  * Active suicidal ideation at screening or baseline, or
  * Previous intent to act on suicidal ideation with a specific plan, preparatory acts, or an actual suicide attempt within the last 3 months

Primary outcomes:
measure: Change Penn Computerized Neuropsychological Testing System (Penn CNP) Scores
timeFrame: 18 months
measure: Change in Test My Brain Scores
timeFrame: 18 months
measure: Change in Dysfunctional Attitudes Scale - Defeatist Beliefs Subscale (DAS-DB) Score
timeFrame: 18 months
measure: Quality of Life Scale - Abbreviated
timeFrame: 18 months
measure: Change in Behavioral Inhibition and Activation Scale (BIS/BAS) - BIS Score
timeFrame: 18 months
measure: Change in Behavioral Inhibition and Activation Scale (BIS/BAS) - BAS Reward Responsiveness Score
timeFrame: 18 months
measure: Change in Behavioral Inhibition and Activation Scale (BIS/BAS) - BAS Drive Score
timeFrame: 18 months
measure: Change in Behavioral Inhibition and Activation Scale (BIS/BAS) - BAS Fun Seeking Score
timeFrame: 18 months
measure: Change in Motivation and Pleasure Scale - Self Report (MAPS-SR) - Social Pleasure Score
timeFrame: 18 months
measure: Change in Motivation and Pleasure Scale - Self Report (MAPS-SR) - Recreational or Work Pleasure Score
timeFrame: 18 months
measure: Change in Motivation and Pleasure Scale - Self Report (MAPS-SR) - Feelings and Motivations About Close, Caring Relationships Score
timeFrame: 18 months
measure: Change in Motivation and Pleasure Scale - Self Report (MAPS-SR) - Motivation and Effort to Engage in Activities Score
timeFrame: 18 months
Secondary outcomes:
measure: COMPASS-10
timeFrame: 18 months
Other outcomes:
measure: BrainHQ Cognitive Training Performance Data
timeFrame: 12 weeks
measure: Tolerability of BrainHQ Cognitive Training & PRIME
timeFrame: 12 weeks
Locations:
city: Duluth
country: United States
facility: Human Development Center
state: Minnesota
city: Minneapolis
country: United States
facility: Hennepin Healthcare
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
Study officials:
affiliation: University of Minnesota Department of Psychiatry and Behavioral Sciences
name: Sophia Vinogradov, MD
role: PRINCIPAL_INVESTIGATOR
References: