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Cognitive Biomarkers in Pediatric Brain Tumor Patients

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ClinicalTrials.gov Identifier: NCT02914067
Recruitment Status : Recruiting
First Posted : September 26, 2016
Last Update Posted : March 14, 2019
Sponsor:
Collaborator:
Children's Discovery Institute
Information provided by (Responsible Party):
Washington University School of Medicine

Brief Summary:
The investigators will focus on two cohorts of brain tumor patients aged, 4-18 years, to answer two critical questions: 1) Can the investigators acquire high quality data relevant to cognitive function during the peri-diagnostic period and, 2) can the investigators develop predictive models for cognitive outcomes using serial examination of functional imaging and cognitive function. Any patient with a newly diagnosed brain tumor aged 4-18 will be eligible for enrollment in cohort 1. Only patients with previously diagnosed tumors of the posterior fossa will be eligible for cohort 2. The rationale for of the focus on these patients is that first, the posterior fossa is the most common location for pediatric brain tumors and therefore this focus will impact the largest segment of this patient population. Second, three tumors commonly occur here, medulloblastoma, ependymoma and pilocytic astrocytoma. These are treated with surgery, radiation and chemotherapy (medulloblastoma), surgery and radiation therapy (ependymoma) or surgery only (pilocytic astrocytoma). Thus, this focus will provide a platform to analyze the impact that different tumor types and different standard treatments have on cognitive dysfunction. Finally, the fact that all subjects will have tumors of the same brain region will control for the effect that tumor location will have on cognitive testing and rsfcMRI. Here, repeated evaluations on and off therapy will provide the necessary data points to establish trajectories of cognitive development and recovery in this population.

Condition or disease Intervention/treatment Phase
Childhood Brain Tumor Other: Neurocognitive testing Device: rsfcMRI Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Cognitive Biomarkers in Pediatric Brain Tumor Patients
Actual Study Start Date : October 26, 2016
Estimated Primary Completion Date : November 30, 2019
Estimated Study Completion Date : January 30, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Brain Tumors

Arm Intervention/treatment
Experimental: Cohort 1
  • Prior to surgery, subjects will have a complete standard of care history and physical exam by the neurosurgeon and then undergo peri-diagnostic neurocognitive testing utilizing the NIH Toolbox Cognitive Battery computer testing software for iPad (will take 45 minutes). The peri-diagnostic period will be defined as the period from first presentation to 2 weeks post-diagnosis or two weeks post-op, whichever is later.
  • Participants will also undergo a rsfcMRI during their standard of care MRI imaging which will add 15 minutes to their scan time
Other: Neurocognitive testing
Device: rsfcMRI
The imaging protocols will be a combined version of a standard of care (SOC) protocol with a research portion. The SOC portion of the pre-surgical scans includes a 3D T2-weighted (T2w) scans and 3D pre- and post-contrast T1-weighted (T1w) images, both at high resolution (1.0 mm3) for use in the intraoperative navigation system. This scan also includes a DTI portion for definition of fiber bundles of interest. The SOC portion of the post-surgical scans includes transverse FLAIR and post-contrast T1w images in all 3 planes. The research portion of the scan will be identical at all 3 time points and include 15 min of rsfcMRI during which the non-sedated subjects will be asked to stay still and awake while looking at a fixation cross

Experimental: Cohort 2
  • Patients with diagnosis of a posterior tumor will undergo neurocognitive testing utilizing the NIH Toolbox. Testing will be every 6 months for children currently receiving therapy and annually for those that have completed all therapy for a total of 2 sessions. During standard of care MRI images, rsfcMRI imaging will be performed which will add 15 minutes of time. rsfcMRI will be obtained every 6 months for children currently receiving therapy and annually for those that have completed therapy for a total of 3 rsfcMRIs for each patient.
  • Patients in Cohort 1 with posterior fossa tumors will also be eligible to continue with the longitudinal assessment as just described. These participants will then undergo repeat neurocognitive testing using the NIH toolbox 6-9 months for an additional 2 testing sessions. rsfcMRI will be obtained during their follow-up imaging at 6-9 month intervals for a total of 3 additional rsfcMRIs (4 total scans).
Other: Neurocognitive testing
Device: rsfcMRI
The imaging protocols will be a combined version of a standard of care (SOC) protocol with a research portion. The SOC portion of the pre-surgical scans includes a 3D T2-weighted (T2w) scans and 3D pre- and post-contrast T1-weighted (T1w) images, both at high resolution (1.0 mm3) for use in the intraoperative navigation system. This scan also includes a DTI portion for definition of fiber bundles of interest. The SOC portion of the post-surgical scans includes transverse FLAIR and post-contrast T1w images in all 3 planes. The research portion of the scan will be identical at all 3 time points and include 15 min of rsfcMRI during which the non-sedated subjects will be asked to stay still and awake while looking at a fixation cross




Primary Outcome Measures :
  1. Identify reliable peri-diagnostic estimators of cognition as measured by neurocognitive testing [ Time Frame: Peri-diagnostic period (from first presentation to 2 weeks post-diagnosis or two weeks post-op, whichever is later) ]
  2. Identify reliable peri-diagnostic estimators of cognition as measured by advanced resting-state functional connectivity MRI (rsfcMRI) data [ Time Frame: Peri-diagnostic period (from first presentation to 2 weeks post-diagnosis or two weeks post-op, whichever is later) ]
  3. Predictors of cognitive recovery in children as determined by multiplexed analyses of a combination of potential biomarkers across multiple modalities (rsfcMRI, structural MRI, NIH Toolbox, patient demographics, treatment information) [ Time Frame: Up to 27 months ]
    As dictated by information theory, properly combining predictors across modalities must increase the accuracy of the prediction algorithm, unless a given modality contains no information about the question of interest (in this case, long-term cognitive outcomes).

  4. Identify reliable peri-diagnostic estimators of brain function as measured by neurocognitive testing [ Time Frame: Peri-diagnostic period (from first presentation to 2 weeks post-diagnosis or two weeks post-op, whichever is later) ]
  5. Identify reliable peri-diagnostic estimators of brain function as measured by advanced resting-state functional connectivity MRI (rsfcMRI) data [ Time Frame: Peri-diagnostic period (from first presentation to 2 weeks post-diagnosis or two weeks post-op, whichever is later) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   4 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Cohort 1 (30 patients will be enrolled to this cohort)

Inclusion Criteria:

  • Between 4 and 18 years of age, inclusive
  • Newly diagnosed primary brain tumor of any location and any histology
  • Life expectancy of at least one year
  • Able to understand and willing to consent or assent to the research proposed, along with consent of legal guardian(s) if applicable

Exclusion Criteria:

  • Presence of visual impairment to an extent that the patient is unable to complete the computer testing
  • Contraindication to MRI scan (i.e. due to cardiac pacemaker)

Cohort 2 (30 patients will enrolled to this cohort. This may include some or all of the patients enrolled to Cohort 1.)

Inclusion Criteria:

  • Between 4 and 18 years of age, inclusive
  • Previous diagnosis of a posterior fossa brain tumor; patients who are either undergoing active treatment for posterior fossa tumor or who have completed treatment will be eligible for study enrollment
  • Life expectancy of at least one year
  • Able to understand and willing to consent assent to the research proposed, along with consent of legal guardian(s) if applicable

Exclusion Criteria:

  • Presence of visual impairment to an extent that the patient is unable to complete the computer testing
  • Contraindication to MRI scan (i.e. due to cardiac pacemaker)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02914067


Contacts
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Contact: Josh Rubin, M.D., Ph.D. 314-286-2790 rubin_j@wustl.edu

Locations
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United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Josh Rubin, M.D., Ph.D.    314-286-2790    rubin_j@wustl.edu   
Principal Investigator: Josh Rubin, M.D., Ph.D.         
Sub-Investigator: Bradley Schlagger, M.D., Ph.D.         
Sub-Investigator: David Limbrick, M.D., Ph.D.         
Sub-Investigator: Joshua Shimony, M.D., Ph.D.         
Sub-Investigator: Nico Dosenbach, M.D., Ph.D.         
Sub-Investigator: Stephanie Perkins, M.D.         
Sub-Investigator: Dennis Barbour, M.D., Ph.D.         
Sponsors and Collaborators
Washington University School of Medicine
Children's Discovery Institute
Investigators
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Principal Investigator: Josh Rubin, M.D., Ph.D. Washington University School of Medicine

Additional Information:
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Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT02914067     History of Changes
Other Study ID Numbers: 201609023
First Posted: September 26, 2016    Key Record Dates
Last Update Posted: March 14, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Washington University School of Medicine:
Pediatric brain tumors
Cognitive deficits
Resting state functional connectivity
NIH toolbox
Additional relevant MeSH terms:
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Brain Neoplasms
Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases