Systemic Biomarkers to Predict Radiation-Induced Neurocognitive Decline (BIO-RIN)

April 8, 2025 updated by: Dr Archya Dasgupta, Tata Memorial Centre

Systemic Biomarkers to Predict Radiation-Induced Neurocognitive Decline in Pediatric and Young Adults With Primary Brain Tumors (BIO-RIN)

Radiation constitutes an integral component in the management of primary brain tumors in pediatric and young adults like medulloblastoma, ependymoma, low-grade glioma, pituitary tumors, etc. A decline in neurocognitive outcomes is a multifactorial effect occurring from the primary disease as well as associated with treatments, including radiation. Since many of these tumors are highly curable, it is crucial to reduce long-term side effects, including memory loss, to improve the quality of life in these patients, leading to better rehabilitation. Radiation-induced neurocognitive deterioration is postulated to occur from multiple factors like neuroinflammation, vascular damage, and depletion of neural stem cells. The proposed study will prospectively evaluate 200 pediatric and young adults with brain tumors treated with radiotherapy. Biological samples (peripheral blood and cerebrospinal fluid) will be procured during routine investigations (an additional amount will be collected for study purposes without the need for additional investigations). Serial blood markers (whenever available pre-operative and before, during, and after completion of radiation) of neuroinflammation and neural markers will be tested in patients undergoing radiation as part of their standard treatment, and correlate with the neurocognitive outcomes measured by age-appropriate Wechsler intelligence scales. Also, the impact of clinical (e.g. age) and radiotherapy parameters like volume, dose of radiation, and technique (photon versus proton therapy) on acute (during radiotherapy) and late systemic inflammatory markers will be analyzed. The study will even provide the opportunity to know the influence of radiation on systemic neuroinflammatory markers in the human population, providing better biological insights into the neurocognitive decline. If proven successful, these biomarkers can be used in routine clinical practice for early intervention to improve neurocognitive function in patients receiving radiation (even for other histology or other patients receiving radiation like brain metastasis).

Study Overview

Status

Recruiting

Conditions

Detailed Description

The requirement would be (approximately 13ml) of peripheral blood sample before starting radiotherapy (Whenever available pre-operative blood samples will be collected). Along with this baseline sample, blood sample will also be collected weekly during the course of fractionated radiation (3ml peripheral blood weekly for 6-7 weeks) and thereafter, 1 month after radiation completion and periodically at regular intervals (every 6-12 months) during follow-up visits (approximately 13ml of blood). The biomarkers and inflammatory panels will be tested using multiplexing kits. Serial blood markers of neuroinflammation (including IL-6, IL-1β, IL-4, IL-10, IL-11, IL-12, TNF-α, IFN-ϒ, GM-CSF, YKL-40, TGB-β, CCL8, ApoJ, ApoE, or ApoA protein with additional neuronal markes like Aβ-42, Aβ-40, BDNF, pNF-H, tau), DNA damage like p53-Binding protein 1, Gamma histone protein from the H2A family (g-H2AX), cell activation and damage like vascular endothelial growth factor (VEGF), vascular cell adhesion molecule Intercellular adhesion molecule 1 (ICAM-1). The plasma samples will be processed using Flow cytometer-based bead assay. This method is best suited for our inflammatory panel detection as its crucial in immunology and clinical research for its ability to assess multiple cytokines simultaneously from limited sample volumes, providing a comprehensive profile of immune responses in various conditions such as inflammation. This will offer us with high sensitivity, specificity, and efficiency with the limited number of samples that we will be collecting. This method is known to be a powerful tool for biomarker discovery, disease monitoring, and understanding complex immune responses. In this assay the Cytokine multiplexing via bead array methods involves the simultaneous detection and quantification of multiple cytokines in a single sample. To perform this technique, microspheres or beads will be coated with capture antibodies specific to different cytokines. These beads will then be incubated with the sample containing cytokines of interest, allowing each cytokine to bind to its corresponding capture antibody on the bead surface. Detection will be achieved by adding fluorescently labelled detection antibodies that will bind to the captured cytokines, thus enabling quantification based on fluorescence intensity using a flow cytometer or similar instrument. Comprehensive neurocognitive evaluation will be conducted using age-appropriate Weschler's intelligence scale or NIMHANS Neuropsychology battery, ACE 3, MOCA, FAB will be conducted. The global scores and other subdomains like verbal quotient (VQ) and performance quotient (PQ) will be obtained as per standard practice. Neurocognitive tests will be performed pre-radiotherapy (baseline), 6 months, 1 year after completion of radiotherapy and thereafter annually. Patients will undergo treatment (radiation, chemotherapy) as per standard practice and followed up every 3-6 months after treatment completion as per standard protocols along with periodic imaging.

Study Type

Observational

Enrollment (Estimated)

200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • India
    • Maharashtra
      • Mumbai, Maharashtra, India, 400012,
        • Recruiting
        • Tata Memorial Hospital (TMH) Parel, and Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Kharghar
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

  1. Age 5-39 years
  2. Histological diagnosis of primary brain tumor
  3. Decision for treatment with radical intent radiotherapy
  4. Signed assent and parental consent form for pediatric age group and signed consent form for adults.

Description

Inclusion Criteria:

  1. Age 5-39 years
  2. Histological diagnosis of primary brain tumor
  3. Decision for treatment with radical intent radiotherapy
  4. Signed assent and parental consent form for pediatric age group and signed consent form for adults.

Exclusion Criteria:

  1. Inability to undergo neurocognitive evaluation
  2. Palliative radiotherapy.
  3. Expected life expectancy < 1 year

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Biomarkers associated with radiation-induced neurocognitive decline
Time Frame: 84 months
Differential values of individual biomarkers will be compared for patient groups with or without neurocognitive decline using Mann Whitney U test and independent t-test.
84 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tata Memorial Centre

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 11, 2025

Primary Completion (Estimated)

February 1, 2032

Study Completion (Estimated)

February 1, 2032

Study Registration Dates

First Submitted

January 11, 2025

First Submitted That Met QC Criteria

January 11, 2025

First Posted (Actual)

January 16, 2025

Study Record Updates

Last Update Posted (Actual)

April 11, 2025

Last Update Submitted That Met QC Criteria

April 8, 2025

Last Verified

April 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 4580

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Data will be kept secured with investigators and can be shared as per institutional ethics committee rules and regulations.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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