Cognitive Testing + Brain Imaging for Childhood Brain Cancer

Recruiting at 1 trial location

Overseen By Stephanie Perkins, M.D.

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Washington University School of Medicine

Disqualifiers: Visual impairment, Cardiac pacemaker, Programmable shunt, Dental braces, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how brain tumors in children affect thinking and brain function over time. It focuses on using brain imaging and cognitive tests to gather data that can predict cognitive outcomes. The trial includes children and young adults between 4 and 30 years old with various brain tumor histories, including those with posterior fossa syndrome, which severely impacts thinking and movement. Eligible participants include those diagnosed with a brain tumor, able to undergo an MRI scan, and willing to participate in cognitive testing, including neurocognitive testing and rsfcMRI (Resting-State Functional Connectivity Magnetic Resonance Imaging). As an unphased trial, this study offers participants the opportunity to contribute to groundbreaking research that could improve future treatments for brain tumors.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It seems the focus is on cognitive testing and brain imaging, so it's best to discuss your specific medications with the trial coordinators.

What prior data suggests that neurocognitive testing and rsfcMRI are safe for children with brain tumors?

Research has shown that both neurocognitive testing and rsfcMRI (resting-state functional MRI) are safe and well-tolerated.

The NIH Toolbox Cognition Battery, used for neurocognitive testing, is a digital tool that assesses thinking skills such as memory and attention. It has proven safe and reliable for both children and adults, including children as young as three years old.

For rsfcMRI, research indicates it is non-invasive and safe. It is often used to map brain activity and assist in planning surgeries for brain tumors. This type of MRI takes slightly longer than a regular MRI scan but does not add any extra risks.

Overall, previous studies have shown both tools to be safe, making them a low-risk option for participation in studies like this one. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it combines cutting-edge neurocognitive testing and advanced brain imaging techniques to gain insights into childhood brain cancer. Unlike standard treatments that focus only on the physical aspects of tumors, this trial uses the NIH Toolbox Cognitive Battery and rsfcMRI imaging to assess and track cognitive functions alongside tumor progression. By integrating these tools, researchers aim to understand how brain cancer and its treatments affect cognitive abilities over time, potentially leading to improved patient care and tailored therapeutic strategies.

What evidence suggests that this trial's treatments could be effective for childhood brain cancer?

Research shows that the NIH Toolbox for neurocognitive testing can effectively identify cognitive weaknesses in children with brain tumors. This tool provides important insights into how these conditions affect the brain. In this trial, participants in various cohorts will undergo neurocognitive testing using the NIH Toolbox. Studies have found that it can detect significant changes in brain networks over time, especially in children who have received certain treatments.

Additionally, research indicates that rsfcMRI, a type of brain scan that examines how different parts of the brain connect at rest, can reveal differences in brain networks in children who have survived brain tumors. Participants in this trial will also undergo rsfcMRI imaging as part of their assessment. This imaging helps researchers understand changes in brain connections, which may relate to the cognitive difficulties these patients experience. Both methods are valuable for understanding and predicting cognitive outcomes in young brain tumor patients. ^{6 7 8 9 10}

Who Is on the Research Team?

Stephanie Perkins, M.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for children aged 4-18 with new brain tumors, focusing on those with posterior fossa tumors or related syndromes. Participants need a life expectancy of at least one year and must consent along with their guardians.

Inclusion Criteria

I am 12-30 years old, was diagnosed with a brain tumor over 3 years ago, can undergo an MRI without sedation, and expect to live at least another year.

Exclusion Criteria

Cohort 1: 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), programmable Shunt

Cohort 2: 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)

I cannot have an MRI due to a pacemaker, dental braces, or needing sedation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Peri-diagnostic

Participants undergo neurocognitive testing and rsfcMRI during the peri-diagnostic period

Up to 2 weeks post-diagnosis or post-op

1 visit (in-person)

Longitudinal Assessment

Participants undergo repeated neurocognitive testing and rsfcMRI imaging every 6-9 months

6-9 months intervals for up to 27 months

3 visits (in-person)

Follow-up

Participants are monitored for cognitive recovery and outcomes

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Neurocognitive testing
• rsfcMRI

Trial Overview

The study aims to collect data on cognitive function using neurocognitive tests and resting-state functional MRI (rsfcMRI) in kids during diagnosis and treatment to predict cognitive outcomes.

How Is the Trial Designed?

Group I: Cohort 4 Arm B Experimental Treatment 2 Interventions

* During standard of care MRI images, rsfcMRI imaging will be performed which will add 15 minutes of scan time. * Will complete cognitive testing using the NIH Toolbox Cognitive Battery * All patients will complete the Attention Deficit/Hyperactivity Disorder (ADHD) Rating Scale - 5 questionnaire. All patients will complete a self-reported assessment of neurological quality of life (QOL). Adult patients (age ≥ 18 years) will complete the adult version of the Quality of Life in Neurological Disorders (Neuro-QOL) Cognitive Function measure. All pediatric patients will complete the pediatric version of the Neuro-QOL Cognitive Function measure. For patients \<18 years of age and for adult patients with parent present, parent/caregiver will complete the PROMIS® Parent Proxy for cognition. All adult patients will complete the Colorado Learning Difficulties Questionnaire (CLDQ). This questionnaire will be completed by parent/caregiver for patients \< 18 years of age.

Group II: Cohort 4 Arm A Experimental Treatment 2 Interventions

Undergo the following MRI images: RSFC MRI, T2/T1 MRI, and DTI. * Will complete cognitive testing using the NIH Toolbox Cognitive Battery * All patients will complete the Attention Deficit/Hyperactivity Disorder (ADHD) Rating Scale - 5 questionnaire. All patients will complete a self-reported assessment of neurological quality of life (QOL). Adult patients (age ≥ 18 years) will complete the adult version of the Quality of Life in Neurological Disorders (Neuro-QOL) Cognitive Function measure. All pediatric patients will complete the pediatric version of the Neuro-QOL Cognitive Function measure. For patients \<18 years of age and for adult patients with parent present, parent/caregiver will complete the PROMIS® Parent Proxy for cognition. All adult patients will complete the Colorado Learning Difficulties Questionnaire (CLDQ). This questionnaire will be completed by parent/caregiver for patients \< 18 years of age.

Group III: Cohort 3 Experimental Treatment 1 Intervention

* During standard of care MRI images, rsfcMRI imaging will be performed which will add 15 minutes of scan time. * rsfcMRI will be obtained annually for total of 3 rsfcMRIs for each patient.

Group IV: Cohort 2 Experimental Treatment 2 Interventions

* 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 3 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 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 3 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).

Group V: Cohort 1 Experimental Treatment 2 Interventions

* 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

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Children's Discovery Institute

Collaborator

Trials

4

Recruited

430+

The Andrew McDonough B+ Foundation

Collaborator

Trials

3

Recruited

220+

Children's Discovery Institute

Collaborator

Trials

6

Recruited

540+

Neurosurgery Research & Education Foundation

Collaborator

Trials

1

Recruited

200+

The Andrew McDonough B+ (Be Positive) Foundation

Collaborator

Trials

1

Recruited

200+

Published Research Related to This Trial

In a study of 49 pediatric brain tumor patients aged 7-18, significant alterations in functional brain network organization were observed, particularly in those who received propofol sedation, indicating that sedation may impact brain function during imaging.

Patients exhibited cognitive deficits in executive function domains over a median follow-up of 3.1 years, with a weak correlation found between decreased segregation in the default mode network and poorer vocabulary scores, suggesting potential predictors for long-term cognitive outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive deficits and altered functional brain network organization in pediatric brain tumor patients. Seitzman, BA., Anandarajah, H., Dworetsky, A., et al.[2023]

A study of 16 adult survivors of childhood cerebellar tumors, averaging 14.9 years post-diagnosis, revealed significant differences in brain functional connectivity compared to matched controls, particularly in networks related to executive functions.

Survivors showed hyperconnectivity in the executive control network, default mode network, and salience network, suggesting that their brain connectivity patterns may reflect adaptations similar to those seen in other neurological conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased frontal functional networks in adult survivors of childhood brain tumors. Chen, H., Wang, L., King, TZ., et al.[2019]

In a study of 43 childhood cancer survivors (aged 7-16) who had completed treatment at least a year prior, it was found that while their overall cognitive performance was normal, they exhibited lower executive functions compared to healthy controls.

The study revealed significant differences in brain connectivity patterns, with survivors showing stronger connectivity in some areas and weaker in others, which correlated with poorer memory performance, indicating lasting effects of non-CNS cancer treatments on brain development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of non-CNS childhood cancer on resting-state connectivity and its association with cognition. Spitzhüttl, JS., Kronbichler, M., Kronbichler, L., et al.[2023]

A study involving 76 newly diagnosed breast cancer patients and 50 healthy controls found that baseline resting state fMRI can predict cognitive impairments, such as executive dysfunction and memory issues, after chemotherapy treatment.

Patients undergoing chemotherapy experienced a significant increase in executive dysfunction and a decrease in memory function over time, highlighting the potential for early neuroimaging assessments to identify those at risk for cognitive decline and improve patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predicting Patient Reported Outcomes of Cognitive Function Using Connectome-Based Predictive Modeling in Breast Cancer. Henneghan, AM., Gibbons, C., Harrison, RA., et al.[2021]

Pediatric brain tumor patients treated with proton therapy showed significant cognitive deficits, particularly in attention and processing speed, with brain network organization being altered as indicated by resting-state functional MRI (rsfMRI).

Higher radiation doses to the right hippocampus were linked to worse cognitive performance in attention and inhibition, as well as decreased segregation in the dorsal attention network, highlighting the impact of radiation on brain function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognition and Brain System Segregation in Pediatric Brain Tumor Patients Treated with Proton Therapy. Dowling, AV., Seitzman, BA., Mitchell, TJ., et al.[2023]

Resting state functional MRI (fMRI) can predict cognitive impairment in breast cancer patients with up to 100% accuracy at long-term follow-up, based on a study of 31 patients evaluated before treatment, after chemotherapy, and one year later.

The study found that specific brain regions, or hubs, were key indicators of cognitive outcomes, suggesting that brain injury may spread over time, highlighting the potential of fMRI in identifying patients at risk for long-term cognitive issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predicting Long-Term Cognitive Outcome Following Breast Cancer with Pre-Treatment Resting State fMRI and Random Forest Machine Learning. Kesler, SR., Rao, A., Blayney, DW., et al.[2020]

Pediatric brain tumor survivors showed poorer neurocognitive performance compared to healthy children, particularly in processing speed, divided attention, and working memory, despite similar parent ratings of day-to-day executive function.

The study found distinct patterns of brain connectivity in survivors, with lower connectivity in the salience network and higher in the default mode network, suggesting an adaptive hyperconnectivity that may relate to their cognitive performance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot Study of Associations Among Functional Connectivity and Neurocognition in Survivors of Pediatric Brain Tumor and Healthy Peers. Seck, S., Kim, YJG., Cunningham, WA., et al.[2022]

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