A Pilot Study to Evaluate Neurocognitive Injury and Longitudinal Changes in White Matter During Radiation Therapy in Children With Primary Brain Tumors

This is a pilot study to assess the changes in white matter, in the brain, in response to radiation therapy and correlate these changes with later declines in cognitive function.

Study Overview

• Status: Terminated
• Conditions: Brain Tumor, Primary
• Intervention / Treatment: Radiation: Cranial Radiotherapy; Device: MRI with Diffusion Tensor Imaging (DTI); Behavioral: Neuro-cognitive Testing (CogState)

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Pediatric patients (age 6-21) who will receive cranial radiotherapy for brian tumors. This could include but is not limited to: low grade glioma, high grade glioma (to include grade III but not grade IV glioma), germ cell tumors, primitive neuroectodermal tumors, craniopharyngioma, or medulloblastoma.
• Patients should, in the estimate of the treating physician, be anticipated to have a median survival of greater than 1 year.

Exclusion Criteria:

• Patients with previous Central Nervous System (CNS) radiation or or CNS tumors that, in the judgement of the investigators, are likely to undergo progression during or shortly after radiotherapy are excluded.
• Patients with glioblastoma, multiforme, gliosarcoma, diffuse pontine glioma, or other tumors presumed to have expected median survival per the investigators of less than 1 year.
• Patients who require sedation for Magnetic Resonance Imagining (MRI)are excluded.
• Patients at risk for nephrogenic systemic sclerosis will be excluded as a safety precaution due to the contrast used in the scans.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Primary Brain Tumor; Patients receiving standard cranial radiotherapy will undergo (1) Magnetic Resonance Imaging (MRI) with Diffusion Tensor Imaging (DTI) and (2) Neuro-cognitive testing (CogState-a computerized software testing system that offers various cognitive assessments based on traditional expansive neurocognitive tests) at four timepoints (Baseline, 3 weeks, 6 weeks and 6 months).

Radiation: Cranial Radiotherapy; Standard cranial radiotherapy administered dependent upon patient and brain tumor type.; Device: MRI with Diffusion Tensor Imaging (DTI); Magnetic Resonance Imaging (MRI) with Diffusion Tensor Imaging (DTI); Behavioral: Neuro-cognitive Testing (CogState); CogState is a computerized software testing system that offers various cognitive assessments based traditional expansive neurocognitive tests.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the Change From Baseline in Perpendicular Diffusivity of Water as Measured by Diffusion Tensor Imaging (DTI) at 3 Weeks and at 6 Weeks Post Radiation Therapy.	Descriptive statistics and plots will be used to determine Diffusion Tensor Imaging (DTI) parameters for various regions in the brain. The mean (across subject) change in DTI parameter for a given region, at a given time, will be used to assess white matter injury.	Baseline, 3 weeks, and 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the Correlation Between Global COGState Scores and the Perpendicular Diffusivity of Water by Diffusion Tensor Imaging at Baseline, 3 Weeks, and 6 Weeks Into Treatment.	Determine the change in cognitive test scores from baseline to time-points early during radiation therapy (3 and 6 weeks) using CogState (a computerized software testing system that offers various cognitive assessments based on expansive neurocognitive tests). Correlate test scores from COGState with changes in Diffusion Tensor Imaging (DTI) at the same timepoints using scatter plots with Pearson and Spearman's correlation coefficients. As a pilot study multiple comparisons will be assessed; however, the working hypothesis is that DTI changes as measured by an increase in diffusivity of water perpendicular to the direction of axonal transport will be measurable even in this acute setting and will correlate with global response as measured on COGState with the sub-domains on executive function anticipated to be most highly correlated.	Baseline, 3 weeks, and 6 weeks
Evaluate the Correlation Between Global COGState Scores, Radiation Dose, and the Perpendicular Diffusivity of Water as Measured by Diffusion Tensor Imaging at 6 Months	Determine the change in cognitive test scores from baseline, at 6 months using CogState (a computerized software testing system that offers various cognitive assessments based on expansive neurocognitive tests). Correlate test scores from COGState with changes in Diffusion Tensor Imaging (DTI) at the same timepoints (Baseline and 6 months) using scatter plots with Pearson and Spearman's correlation coefficients. As a pilot study multiple comparisons will be assessed; however, the working hypothesis based upon results in adults treated with radiation therapy is that DTI changes as measured by an increase in diffusivity of water perpendicular to the direction of axonal transport will correlate with changes in global response as measured on COGState with the sub-domains on executive function most highly correlated. In addition, these regional changes in DTI will be directly related to the radiation doses received in these regions.	6 months

Collaborators and Investigators

• Sponsor: University of Michigan Rogel Cancer Center
• Investigators: Principal Investigator: Carl Koschmann, M.D., University of Michigan Rogel Cancer Center

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: November 26, 2013
• First Submitted That Met QC Criteria: December 4, 2013
• First Posted (Estimate): December 10, 2013

Study Record Updates

• Last Update Posted (Estimate): December 30, 2016
• Last Update Submitted That Met QC Criteria: November 11, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Neoplasms
• Other Study ID Numbers: UMCC 2012.117