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Is Cognitive Training Neuroprotective in Early Psychosis?

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ClinicalTrials.gov Identifier: NCT03049800
Recruitment Status : Recruiting
First Posted : February 10, 2017
Last Update Posted : May 6, 2019
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
University of Minnesota - Clinical and Translational Science Institute

Tracking Information
First Submitted Date January 26, 2017
First Posted Date February 10, 2017
Last Update Posted Date May 6, 2019
Actual Study Start Date June 12, 2017
Estimated Primary Completion Date June 12, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: May 1, 2019)
  • Longitudinal changes in gray matter volume [ Time Frame: 1 year ]
    The investigators will conduct 3 7T and 3 Prisma 3T structural and functional MRI scans over a period of 10-12 months to observe any changes in gray matter volume between cohorts and over time. The investigators will examine gray matter volume in the left Heschl gyrus (HS), left planum temporale (PT), and the prefrontal, parietal, and hippocampal cortices.
  • Longitudinal changes in white matter integrity [ Time Frame: 1 year ]
    The investigators will conduct 3 7T and 3 Prisma 3T diffusion weighted MRI scans over a period of 10-12 months to observe any changes in white matter integrity between cohorts and over time. The investigators will examine changes in the left temporal lobe, left superior longitudinal fasiculus, left arcuate fasciculus, left uncinated fasciculus, left uncinated fasciculus, cingulum bundle, and corpus callosum.
  • Association of changes in gray matter volume and white matter integrity with changes in clinical, cognitive and functional outcome measures in FEP participants [ Time Frame: 1 year ]
    The investigators will compare the longitudinal changes in gray matter volume and in white matter integrity to the changes in measures of clinical, cognitive, and functional assessments in the associated randomized controlled study of cognitive training (NCT03079024), between cohorts and over time. The investigators will examine the differences between participants who received cognitive training and those who received treatment as usual.
Original Primary Outcome Measures
 (submitted: February 9, 2017)
  • Changes in Functional 7T MRI scans of the auditory cortex (superior temporal gyrus) [ Time Frame: 1 year ]
    The investigators will conduct 2 7T MRI scans over the course of one year to observe any changes in the functional, structural, and diffusion weight imaging between cohorts and over time. The investigators will be observing changes in neural tissue in the auditory cortex (superior temporal gyrus), and possibly in other related cortical regions.
  • Changes in Structural 7T MRI scans of the auditory cortex (superior temporal gyrus) [ Time Frame: 1 year ]
    The investigators will conduct 2 7T MRI scans over the course of one year to observe any changes in the structural imaging between cohorts and over time. The investigators will be observing changes in neural tissue in the auditory cortex (superior temporal gyrus), and possibly in other related cortical regions.
  • Changes in diffusion weight 7T MRI scans of the auditory cortex (superior temporal gyrus) [ Time Frame: 1 year ]
    The investigators will conduct 2 7T MRI scans over the course of one year to observe any changes in the diffusion weight imaging between cohorts and over time. The investigators will be observing changes in neural tissue in the auditory cortex (superior temporal gyrus), and possibly in other related cortical regions.
  • Changes in white matter integrity [ Time Frame: 1 year ]
    The investigators will conduct 2 7T MRI scans over the course of one year to observe any changes in white matter integrity between cohorts and over time.
Change History Complete list of historical versions of study NCT03049800 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: May 1, 2019)
  • Longitudinal changes in extracellular volume fraction [ Time Frame: 1 year ]
    The investigators will examine changes in MRI diffusion imaging of this novel biomarker that may represent neuroinflammation. The investigators will examine the changes between cohorts and over time.
  • Association between longitudinal changes in extracellular volume fraction and changes in clinical, cognitive, and functional outcomes in FEP participants. [ Time Frame: 1 year ]
    The investigators will compare the longitudinal changes in extracellular volume fraction to the changes in measures of clinical, cognitive, and functional assessments in the associated randomized controlled study of cognitive training (NCT03079024), between cohorts and over time. The investigators will examine the differences between participants who received cognitive training and those who received treatment as usual.
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Is Cognitive Training Neuroprotective in Early Psychosis?
Official Title Is Cognitive Training Neuroprotective in Early Psychosis?
Brief Summary The purpose of this study is to perform longitudinal high-resolution 7T MRI and Prisma 3T MRI in participants with first-episode psychosis (FEP) enrolled in our ongoing randomized controlled clinical trial (RCT) of cognitive training. The investigators seek to determine whether a 12-week course of intensive cognitive training of auditory processing in young FEP patients delivered remotely as a stand-alone treatment is neuroprotective against neural tissue loss in auditory cortex (superior temporal gyrus, STG), and possibly in other cortical regions. The investigators will also observe the effects of training on white matter integrity in the brain.
Detailed Description

The current protocol seeks to examine whether cognitive training can prevent accelerated gray matter loss and promote changes in the functional connectome in first-episode psychosis patients. Specifically, we aim to use Prisma 3T and 7T imaging to examine functional, structural, and diffusion weighted images to determine whether these treatments can influence neural plasticity. Scanning will be done at the Center for Magnetic Resonance Research (CMRR) at the University of Minnesota. Participants will complete three approximately one-hour scanning sessions on the 3T Siemens Prisma scanner and three approximately one-hour scanning sessions on the 7T-AS scanner. We aim to use scan sequences compatible with the Human Connectome Project both for purposes of cross collaboration and data sharing.

This study will seek to enroll 80 participants. 60 participants will be considered First Episode Psychosis (FEP) patients, meaning that they have been diagnosed with a psychotic illness and have started receiving treatment at a First Episode Psychosis clinic (following the NAVIGATE model) within the last two years prior to enrollment. These participants will be recruited from a separate study protocol conducted by Dr. Sophia Vinogradov which examines remote cognitive training in FEP subjects (Minnesota Community-Based Cognitive Training in Early Psychosis, NCT03079024). 20 of these participants will receive treatment as usual (TAU), 20 will be assigned to Targeted Cognitive Training (TCT), and 20 will be assigned to Generalized Cognitive Exercises (GCE). Additionally, the investigators will enroll 20 healthy, age and gender matched controls (HC). All participants will undergo one 7T MRI and one Prisma scan at three time points: Baseline; Post-Intervention/12-weeks; and 6 month follow up.

The three 3T scan sessions will be matched as closely as possible, given hardware limitations, to the HCP 3T imaging protocol described here: http://protocols.humanconnectome.org/HCP/3T/imaging-protocols.html. This will include ~16 minutes of 3D structural imaging using MP-RAGE and T2-weighted scans, ~14 minutes of resting state fMRI relying on a gradient-echo EPI sequence, and 18 minutes of diffusion weighted MRI relying on a spin-echo EPI sequence. Scan parameters for acquisitions will seek to match the HCP Lifespan data acquired to date on the CMRR Prisma 3T.

For 7T scans, we will collect a standard T1-weighted MP2-RAGE structural scan, 12 minutes of resting fMRI using standard gradient-echo EPI sequences, and a diffusion-weighted DTI sequence compatible both with HCP and 7T-AS hardware. To maximize use of high-resolution imaging techniques while balancing ease of access and use, we aim to use the Siemens 7T-AS scanner with the NOVA 32-Channel head coil optimized for both structural and functional imaging.

Specific Aims

  1. Use the Siemens Prisma 3T MRI system and 7T MRIs to investigate longitudinal changes in brain gray matter volume in left Heschl gyrus (HG) and left planum temporale (PT) between baseline, post-training (approximately 12 weeks), and 12 months, within 20 FEP subjects who have undergone targeted cognitive training of auditory processing and 20 FEP subjects who have undergone general cognitive exercises, as compared to 20 treatment-as-usual FEP subjects and 20 age and gender matched healthy controls. Secondarily, we will also examine gray matter volume changes in prefrontal, parietal, and left hippocampual cortex.
  2. Use the Siemens Prisma 3T MRI system and 7T MRI to investigate longitudinal changes in left temporal lobe white matter integrity between baseline, post-training (approximately 12 weeks), and 12 months, within 20 FEP subjects who have undergone targeted cognitive training of auditory processing and 20 FEP subjects who have undergone general cognitive exercises, as compared to 20 treatment-as-usual FEP subjects and 20 age and gender matched healthy controls. Secondarily, we will also examine changes in left superior longitudinal fasiculus, left arcuate fasciculus, left uncinated fasciculus, left uncinated fasciculus, cingulum bundle, and corpus callosum.
  3. Investigate the association of changes in brain gray matter volume and white matter integrity with changes in clinical, cognitive and functional outcome measures in the FEP subjects who have undergone training.

Exploratory Aims

  1. Use Prisma 3T and 7T MRI to explore longitudinal changes between baseline, post-training (approximately 12 weeks), and at 6 month follow-up, in a novel putative MRI diffusion imaging biomarker that may represent neuroinflammation (extracellular volume fraction) in 20 FEP subjects who have undergone targeted cognitive training and 20 FEP subjects who have undergone general cognitive exercises, as compared to 20 treatment-as-usual FEP subjects and 20 age and gender matched healthy controls.
  2. Investigate the association of these changes with clinical, cognitive, and functional outcomes in the subject groups.
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population

FEP participants will be currently enrolled in "Minnesota Community Based Cognitive Training in Early Schizophrenia," NCT03079024. This study examines cognitive training delivered remotely to patients who receive treatment for FEP at a NAVIGATE-model clinic. There are three groups in this study: one receives targeted cognitive training (TCT); one receives general cognitive exercises (GCE); and the third receives treatment-as-usual (TAU). Cognitive training groups complete up to 30 hours of training over 6-12 weeks. 20 participants in each arm will be recruited for a total of 60.

Control subjects who are matched to the FEP participants in age and gender will be recruited from the community. We will recruit a total of 20 psychologically and physically healthy adults for this study.

Condition
  • Psychosis
  • Healthy
Intervention Device: Magnetic Resonance Imaging
Functional, structural, and diffusion weighted imaging conducted with a 7T-PS scanner and a Prisma 3T scanner.
Study Groups/Cohorts
  • FEP - Treatment as Usual
    First Episode Psychosis patients who receive treatment as usual while participating in an associated randomized controlled trial examining the effect of computerized cognitive training.
    Intervention: Device: Magnetic Resonance Imaging
  • FEP - Targeted Cognitive Training
    First Episode Psychosis patients who receive targeted cognitive training exercises while participating in an associated randomized controlled trial examining the effect of computerized cognitive training.
    Intervention: Device: Magnetic Resonance Imaging
  • FEP - General Cognitive Exercises
    First Episode Psychosis patients who receive general cognitive exercises while participating in an associated randomized controlled trial examining the effect of computerized cognitive training.
    Intervention: Device: Magnetic Resonance Imaging
  • Healthy Controls
    Age and gender matched controls who are psychologically and physically healthy will be recruited from the community to participate in this cohort.
    Intervention: Device: Magnetic Resonance Imaging
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: May 1, 2019)
80
Original Estimated Enrollment
 (submitted: February 9, 2017)
60
Estimated Study Completion Date June 12, 2021
Estimated Primary Completion Date June 12, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria

First Episode Psychosis (FEP) Participants

Inclusion Criteria:

  • Enrolled in the Mini-COTES randomized controlled trial examining cognitive training in First Episode Psychosis (NCT03079024)
  • Clinical diagnosis of schizophrenia, schizoaffective disorder, schizophreniform disorder, major depressive disorder with psychotic features, bipolar disorder with psychotic features, psychosis disorder not otherwise specified, or unspecified schizophrenia spectrum disorder, and started receiving treatment services at a First Episode Psychosis Program within the last two years
  • Good general physical health
  • Age between 16 and 35 (inclusive)
  • Fluent in written and spoken English
  • No neurological disorder (diagnosis of Autism Spectrum Disorder is allowed)
  • Achieved clinical stability, defined as outpatient status for at least one month prior to study participation, stable doses of psychiatric medications for at least one month prior to study participation
  • Women who are pregnant or breastfeeding may participate in this study

Healthy Controls (HC) Participants

Inclusion Criteria:

  • Age between 16 and 35 (inclusive)
  • Fluent in English
  • Good general physical health
  • No neurological disorder
  • No current or past diagnosis of a psychotic disorder, mood disorder, or anxiety disorder

All Participants

Exclusion Criteria:

  • Unable to provide informed consent (or assent if under 18)
  • Parents do not provide consent for participants under 18
  • Clinically significant substance abuse that is impeding the subject's ability to participate fully during recruitment, assessment, or training (is unable to remain sober for assessments).
  • Cannot pass the CMRR safety screen for receiving an MRI
  • Participant does not comply with study procedures. Exclusion is determined at PI discretion.
Sex/Gender
Sexes Eligible for Study: All
Ages 16 Years to 35 Years   (Child, Adult)
Accepts Healthy Volunteers Yes
Contacts
Contact: Riley Capizzi 612-626-5167 minicotes@umn.edu
Contact: Brandon Schemitzler 612-626-0953 minicotes@umn.edu
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT03049800
Other Study ID Numbers 7T R21
R21MH110208-01A1 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement
Plan to Share IPD: Yes
Plan Description: Data from this study will be shared with the NIMH Data Archive, ID C2788. Additionally, interested collaborators may reach out to the PI directly to share data.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Analytic Code
Time Frame: Supporting information will be made available one year after completion of all study procedures, and will be available indefinitely.
Access Criteria: Interested researchers may access this data using the NIMH Data Archive by following the requirements of this registry. Those who would like to see other supporting information may reach out to the PI directly. The PI may share data at their discretion, according to institutional policies, which may include entering into a Data Use Agreement and accessing data within a data shelter.
Responsible Party University of Minnesota - Clinical and Translational Science Institute
Study Sponsor University of Minnesota - Clinical and Translational Science Institute
Collaborators National Institute of Mental Health (NIMH)
Investigators
Principal Investigator: Sophia Vinogradov, MD University of Minnesota Department of Psychiatry
PRS Account University of Minnesota - Clinical and Translational Science Institute
Verification Date May 2019