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

• Sponsor: University of Michigan Rogel Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02006407
• Collaborator: (none)
• Enrollment: 5
• Location: 1
• Arm: 1
• Duration (Months): 30
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Brain Tumor, Primary	Radiation: Cranial Radiotherapy; Device: MRI with Diffusion Tensor Imaging (DTI); Behavioral: Neuro-cognitive Testing (CogState)	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: A Pilot Study to Evaluate Neurocognitive Injury and Longitudinal Changes in White Matter During Radiation Therapy in Children With Primary Brain Tumors
• Study Start Date: Jun 1, 2013
• Actual Primary Completion Date: Aug 1, 2015
• Actual Study Completion Date: Dec 1, 2015

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. 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. [Baseline, 3 weeks, and 6 weeks]

   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.

Secondary Outcome Measures

1. 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. [Baseline, 3 weeks, and 6 weeks]

   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.

2. Evaluate the Correlation Between Global COGState Scores, Radiation Dose, and the Perpendicular Diffusivity of Water as Measured by Diffusion Tensor Imaging at 6 Months [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Michigan Cancer Center	Ann Arbor	Michigan	United States	48109

Sponsors and Collaborators

• University of Michigan Rogel Cancer Center

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Michigan Rogel Cancer Center
• ClinicalTrials.gov Identifier: NCT02006407
• Other Study ID Numbers: UMCC 2012.117
• First Posted: Dec 10, 2013
• Last Update Posted: Dec 30, 2016
• Last Verified: Nov 1, 2016

• Additional relevant MeSH terms: Brain Neoplasms

Study Results

Participant Flow

Arm/Group Title	Primary Brain Tumor
Arm/Group Description	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). Cranial Radiotherapy: Standard cranial radiotherapy administered dependent upon patient and brain tumor type. MRI with Diffusion Tensor Imaging (DTI): Magnetic Resonance Imaging (MRI) with Diffusion Tensor Imaging (DTI) Neuro-cognitive Testing (CogState): CogState is a computerized software testing system that offers various cognitive assessments based traditional expansive neurocognitive tests.
Period Title: Overall Study
STARTED	5
COMPLETED	5
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Primary Brain Tumor
Arm/Group Description	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). Cranial Radiotherapy: Standard cranial radiotherapy administered dependent upon patient and brain tumor type. MRI with Diffusion Tensor Imaging (DTI): Magnetic Resonance Imaging (MRI) with Diffusion Tensor Imaging (DTI) Neuro-cognitive Testing (CogState): CogState is a computerized software testing system that offers various cognitive assessments based traditional expansive neurocognitive tests.
Overall Participants	5
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	14
Gender (Count of Participants)
Female	2 40%
Male	3 60%

Outcome Measures

1. Primary Outcome

Title	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.
Description	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.
Time Frame	Baseline, 3 weeks, and 6 weeks

Outcome Measure Data

Analysis Population Description

Because the outcome measure was CHANGE FROM BASELINE to 3 and 6 weeks, and data were not able to be collected at 3 and 6 weeks, the outcome measure could not be analyzed

Arm/Group Title	Primary Brain Tumor
Arm/Group Description	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). Cranial Radiotherapy: Standard cranial radiotherapy administered dependent upon patient and brain tumor type. MRI with Diffusion Tensor Imaging (DTI): Magnetic Resonance Imaging (MRI) with Diffusion Tensor Imaging (DTI) Neuro-cognitive Testing (CogState): CogState is a computerized software testing system that offers various cognitive assessments based traditional expansive neurocognitive tests.
Measure Participants	0

2. Secondary Outcome

Title	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.
Description	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.
Time Frame	Baseline, 3 weeks, and 6 weeks

Outcome Measure Data

Analysis Population Description

Data can not be accessed due to technical difficulties with the COGState server.

Arm/Group Title	Primary Brain Tumor
Arm/Group Description	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). Cranial Radiotherapy: Standard cranial radiotherapy administered dependent upon patient and brain tumor type. MRI with Diffusion Tensor Imaging (DTI): Magnetic Resonance Imaging (MRI) with Diffusion Tensor Imaging (DTI) Neuro-cognitive Testing (CogState): CogState is a computerized software testing system that offers various cognitive assessments based traditional expansive neurocognitive tests.
Measure Participants	0

3. Secondary Outcome

Title	Evaluate the Correlation Between Global COGState Scores, Radiation Dose, and the Perpendicular Diffusivity of Water as Measured by Diffusion Tensor Imaging at 6 Months
Description	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.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Data can not be accessed due to technical difficulties with the COGState server.

Arm/Group Title	Primary Brain Tumor
Arm/Group Description	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). Cranial Radiotherapy: Standard cranial radiotherapy administered dependent upon patient and brain tumor type. MRI with Diffusion Tensor Imaging (DTI): Magnetic Resonance Imaging (MRI) with Diffusion Tensor Imaging (DTI) Neuro-cognitive Testing (CogState): CogState is a computerized software testing system that offers various cognitive assessments based traditional expansive neurocognitive tests.
Measure Participants	0

Adverse Events

Time Frame	Data on adverse events were collected from the time of the initial study intervention through the 12 month post baseline visit.
Adverse Event Reporting Description	Only events related to the study intervention (MRI and Neuro-cognitive Testing) were reported. No adverse events related to these interventions were reported.
Arm/Group Title	Primary Brain Tumor
Arm/Group Description	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). Cranial Radiotherapy: Standard cranial radiotherapy administered dependent upon patient and brain tumor type. MRI with Diffusion Tensor Imaging (DTI): Magnetic Resonance Imaging (MRI) with Diffusion Tensor Imaging (DTI) Neuro-cognitive Testing (CogState): CogState is a computerized software testing system that offers various cognitive assessments based traditional expansive neurocognitive tests.
All Cause Mortality
	Primary Brain Tumor
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Primary Brain Tumor
	Affected / at Risk (%)	# Events
Total	0/5 (0%)
Other (Not Including Serious) Adverse Events
	Primary Brain Tumor
	Affected / at Risk (%)	# Events
Total	0/5 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.