Mechanisms of Response to Therapeutic Intervention in Clinical High Risk (CHR) for Psychosis
NCT Number: NCT06542640
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Psychosis; Schizophrenia-Like|Healthy Controls
Interventions: DEVICE: Mb-rt-fMRI-NFB|DEVICE: Sham mb-rt-fMRI-NFB|DEVICE: rTMS|DEVICE: Sham rTMS
Sponsor: Beth Israel Deaconess Medical Center
Collaborators: Shanghai Jiao Tong University School of Medicine|Florida A&M University|Brigham and Women's Hospital|Massachusetts General Hospital|VA Boston Healthcare System|National Institute of Mental Health (NIMH)
Sex: ALL
Age: CHILD, ADULT
Enrollment: 300
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: QUADRUPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2024-09-01
Completion Date: 2027-06-30

Summary:
This study, "Psychobiological Follow-up Study of Transition from Prodrome to Early Psychosis", will be conducted in collaboration with the Shanghai Mental Health Center (SMHC) and several data processing sites in the United States. The current study builds on findings from the investigator's previous work that identified several biomarkers in participants at clinical high risk (CHR) for psychosis that may be related to clinical outcomes such as the development of psychosis. This study responds to the critical need to understand links between biomarkers (could be clinical, cognitive, biological or other abnormalities) and later clinical outcomes.

Participants will receive either one of two real interventions or one of two sham (a procedure that looks like the real treatment but is not) interventions, involving either: 1. repetitive transcranial magnetic stimulation (rTMS)1; or 2. mindfulness-based real time fMRI neurofeedback (mb-rt-fMRI-NFB). Both procedures will measure brain capacity for change in CHR individuals, thus paving the way forward for future therapeutic interventions.

The main hypotheses to be addressed by this study are:

1. - Following real interventions, novel biomarkers will be more effective predictors of clinical outcome than standard biomarkers in participants at CHR for psychosis
2. - Following real interventions, novel biomarkers will be more effective predictors of clinical outcomes in participants who received the real intervention than in participants who received sham treatments
3. - The novel interventions will reduce biomarker abnormalities in individuals with CHR relative to their own baselines and relative to healthy controls (HC)
4. - The sham interventions will will not reduce biomarker abnormalities in individuals with CHR relative to their own baselines or relative to HC

Primary Outcome Measures: mb-rt-fMRI-NFB intervention: functional connectivity, Context-dependent changes in functional connectivity (i.e., coupling) between brain regions will be measured by statistical software programs as Pearson correlation coefficients between brain regions whose activity depends on an interaction between psychological context (the task) and physiological state (the time course of brain activity), 1 month, 1 year, 2 years|rTMS intervention: functional connectivity, Context-dependent changes in functional connectivity (i.e., coupling) between brain regions will be measured by statistical software programs as Pearson correlation coefficients between brain regions whose activity depends on an interaction between psychological context (the task) and physiological state (the time course of brain activity), 1 month, 1 year, 2 years
Secondary Outcome Measures: Clinical, Changes in Clinical High Risk clinical function from baseline will measured using the Structured Interview for Psychosis Risk Syndromes, specifically the Scale for Psychosis Risk Symptoms and the Criteria for Psychosis Risk Syndromes, 1 month, 1 year, 2 years|Neuropsychological function: verbal learning, Changes in verbal learning from baseline will be measured in the Clinical High Risk participants using the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery: Hopkins Verbal Learning Test - Revised, 1 month, 1 year, 2 years|Neuropsychological function: visual learning, Changes in visual learning from baseline will be measured in the Clinical High Risk participants using the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery: Brief Visuospatial Memory Test - Revised, 1 month, 1 year, 2 years|Neuropsychological function: visual-spatial / speed of processing, Changes in visual-spatial speed of processing from baseline will be measured in the Clinical High Risk participants using the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery: Trail Making Test, 1 month, 1 year, 2 years|Neuropsychological function: verbal fluency / speed of processing, Changes in verbal fluency / speed of processing from baseline will be measured in the Clinical High Risk participants using the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery: Category Fluency: Animal Naming Test, 1 month, 1 year, 2 years|Neuropsychological function: visual-motor / speed of processing, Changes in visual-motor / speed of processing from baseline will be measured in the Clinical High Risk participants using the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery: Brief Assessment of Cognition in Schizophrenia: Symbol Coding, 1 month, 1 year, 2 years|Neuropsychological function: attention, Changes in attention from baseline will be measured in the Clinical High Risk participants using the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery: Continuous Performance Test: Identical Pairs Version, 1 month, 1 year, 2 years|Neuropsychological function: working memory, Changes in working memory from baseline will be measured in the Clinical High Risk participants using the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery: Wechsler Memory Scale - Third Edition: Spatial Span, 1 month, 1 year, 2 years|Neuropsychological function: reasoning and problem solving, Changes in reasoning and problem solving from baseline will be measured in the Clinical High Risk participants using the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery: Neuropsychological Assessment Battery: Mazes, 1 month, 1 year, 2 years|Event Related Potentials, Changes in Clinical High Risk participant's electrophysiological function from baseline will be measured through measures of wave amplitudes and latencies in 'P300 Oddball' and 'P300 Novel' paradigms, 1 month, 1 year, 2 years|Natural Language Processing: Linguistic, Changes in Clinical High Risk participant's natural language function from baseline will be measured linguistically using machine learning: semantic coherence, 1 month, 1 year, 2 years|Natural Language Processing: Acoustic, Changes in Clinical High Risk participant's natural language function from baseline will be measured acoustically using machine learning: pauses in words, 1 month, 1 year, 2 years|Structural MRI, Changes in Clinical High Risk participant's cortical gray matter brain function will be measured through cortical thickness, 1 month, 1 year, 2 years|Diffusion Tensor Imaging, Changes in Clinical High Risk participant's brain white matter function will be measured using 'fractional anisotropy', which is a measurement of the directionality of water diffusion in white matter, which is used in diffusion imaging to assess the density of white matter fibers, axonal diameter, and myelination, 1 month, 1 year, 2 years