NST-SPARK Open-Label Phase 1 STTR (IGNITE)

The investigators will evaluate NST-SPARK v2.0 in a 12-week, single-arm, open-label clinical trial in 30 individuals with schizophrenia spectrum disorders (SSD) who exhibit moderate to severe negative symptoms. Participants will be recruited from stable outpatient populations at Zucker Hillside Hospital (n=20) and the University of Pennsylvania (n=10). The primary objective of the study is to assess the feasibility and acceptability of NST-SPARK, along with generating preliminary evidence of efficacy in reducing experiential negative symptoms. Secondary objectives include evaluating changes in defeatist beliefs, effort expenditure, affect, global functioning, and overall symptom burden, as well as characterizing user engagement and collecting qualitative feedback to inform future product development. The investigators hypothesize that NST-SPARK will demonstrate strong feasibility and acceptability, defined by mean Acceptability of Intervention Measure (AIM) and Feasibility of Intervention Measure (FIM) scores greater than 3.5, and adherence exceeding 75% of prescribed sessions. The investigators further expect to observe moderate improvements in experiential negative symptoms and reductions in defeatist beliefs. Eligible participants will be adults aged 18 and older with a diagnosis of schizophrenia, schizoaffective disorder, schizophreniform disorder, or unspecified psychotic disorder. All participants must be clinically stable, with no recent exacerbation of positive symptoms, hospitalization, or medication changes within the prior month. Participants must exhibit moderate to severe negative symptoms, defined by a CAINS Motivation and Pleasure (MAP) subscale score greater than 17, and must have sufficient cognitive and functional capacity to consent and participate in a longitudinal study. Participants will be excluded if they present a significant safety risk (including recent suicidal or homicidal ideation), have impairments that would prevent use of a smartphone-based intervention (e.g., severe sensory or physical limitations), have an estimated IQ below 70, or demonstrate cognitive or psychiatric conditions that would limit engagement (including active mood episodes such as mania or major depression). Participants will access NST-SPARK either on their personal compatible smartphone or on a study-provided device. A trained research coordinator at each site will support onboarding, conduct assessments, and provide technical assistance. Outcome assessments will be conducted by centralized raters blinded to study conditions for key endpoints. Participants will be instructed to engage with the application at least three times per week over the 12-week treatment period, with the option for more frequent use. Based on prior experience in this population, approximately 20 participants are anticipated to complete the study. Study activities will begin with a screening phase to confirm eligibility, followed by baseline assessments prior to initiating treatment. Participants will then complete interim follow-up assessments at weeks 3, 6, and 9, and a final endpoint assessment at week 12. Recruitment will begin after finalization of the NST-SPARK v2.0 platform, with enrollment occurring over approximately 10 months at a rate of 3-4 participants per month. This will be followed by a three-month period for completion of follow-up assessments and an additional three months for data analysis, manuscript preparation, and planning of a subsequent Phase II study. Input from individuals with lived experience will be incorporated throughout the trial to contextualize findings and inform future study design. Participants will undergo a comprehensive assessment battery spanning diagnostic, symptomatic, behavioral, and functional domains. Diagnostic eligibility will be confirmed during screening using structured clinical interviews focused on mood and psychotic disorders, with additional screening to exclude individuals with significant depressive symptoms. All analyses will be conducted on available data regardless of adherence to the intervention. Given the exploratory nature of this early-stage study, adjustments for multiple comparisons will not be applied. Approximately 20 participants are anticipated to complete the study after accounting for expected attrition. This sample size provides sufficient statistical power to detect moderate treatment effects in within-subject analyses. Key indicators of success include demonstration of strong feasibility and acceptability, meaningful engagement with the intervention, and at least moderate improvement in experiential negative symptoms. In addition, successful completion of this study is expected to yield a trial-ready version of NST-SPARK capable of delivering a full 12-week therapeutic experience, incorporating both cognitive-behavioral and augmented reality components.

• Global Functioning [Time frame: This measure will be collected at baseline and at the 12-week endpoint.]
• Defeatist Beliefs [Time frame: This measure will be collected at baseline, during the interim 3-, 6-, and 9-week timepoints, and at the 12-week endpoint.]
• Positive Self Regard [Time frame: This measure will be collected at baseline, during the interim 3-, 6-, and 9-week timepoints, and at the 12-week endpoint.]
• Effort Expenditure [Time frame: This measure will be collected at baseline, during the interim 3-, 6-, and 9-week timepoints, and at the 12-week endpoint.]
• Loneliness [Time frame: This measure will be collected at baseline and at the 12-week endpo]
• Overall Psychosis Symptoms [Time frame: This measure will be collected at baseline and at the 12-week endpoint.]
• Qualitative Feedback on App Experience [Time frame: This measure will be collected at the 12-week endpoint.]
• Vocal Biomarker Composite Score [Time frame: This measure will be collected at baseline and at the 12-week endpoint.]