Brain TumorsBIO-RINNCT06779487
Systemic Biomarkers to Predict Radiation-Induced Neurocognitive Decline
An observational study of Brain Tumors and Medulloblastoma, run by Tata Memorial Centre at 1 site in India.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 5 to 39 years
- Conditions the study is for
- Brain Tumors, Medulloblastoma, Glioma
- How many people
- 200 participants
- Where
- 1 siteIndia
- Study dates
- 11 Feb 2025to Feb 2032
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 39 years
- All sexes
- No healthy volunteers
- Child, Adult
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.
Who may be able to join
- Age 5-39 years
- Histological diagnosis of primary brain tumor
- Decision for treatment with radical intent radiotherapy
- Signed assent and parental consent form for pediatric age group and signed consent form for adults.
Who cannot join
- Inability to undergo neurocognitive evaluation
- Palliative radiotherapy.
- Expected life expectancy < 1 year
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
India1 site, 1 recruiting
- Recruiting
Tata Memorial Hospital (TMH) Parel, and Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Kharghar
Mumbai, Maharashtra, 400012,
Dr. Archya Dasgupta, MBBS, MD, 91-22-24177000 ext. 6861/6017, archya1010@gmail.com
About this study
Official title: 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).
Read the 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.
- Conditions
- Brain Tumors, Medulloblastoma, Glioma, Ependymoma
- Keywords
- Brain Tumor, Radiotherapy, Proton Beam Therapy, Neuro-cognition, Bio-markers
- Medical subject headings
- Brain Neoplasms, Medulloblastoma, Glioma, Ependymoma
What is being measured
The primary outcome is the main question the study is designed to answer.
Biomarkers associated with radiation-induced neurocognitive decline
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.
Measured: 84 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2025
- Study start11 Feb 2025
- Primary completionFeb 2032 (estimated)
- Study completionFeb 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Brain TumorsStudies of the same condition, open and under way.
- More trials run by Tata Memorial CentreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tata Memorial Centre
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr Archya Dasgupta, Tata Memorial Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06779487
- Sponsor's protocol ID
- 4580
- Acronym
- BIO-RIN
- Status last verified
- Apr 2025
- First submitted
- 11 Jan 2025
- Last updated
- 11 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Data will be kept secured with investigators and can be shared as per institutional ethics committee rules and regulations.
Publications
Ayoub R, Ruddy RM, Cox E, Oyefiade A, Derkach D, Laughlin S, Ades-Aron B, Shirzadi Z, Fieremans E, MacIntosh BJ, de Medeiros CB, Skocic J, Bouffet E, Miller FD, Morshead CM, Mabbott DJ. Assessment of cognitive and neural recovery in survivors of pediatric brain tumors in a pilot clinical trial using metformin. Nat Med. 2020 Aug;26(8):1285-1294. doi: 10.1038/s41591-020-0985-2. Epub 2020 Jul 27.
PubMed 32719487Brown PD, Pugh S, Laack NN, Wefel JS, Khuntia D, Meyers C, Choucair A, Fox S, Suh JH, Roberge D, Kavadi V, Bentzen SM, Mehta MP, Watkins-Bruner D; Radiation Therapy Oncology Group (RTOG). Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial. Neuro Oncol. 2013 Oct;15(10):1429-37. doi: 10.1093/neuonc/not114. Epub 2013 Aug 16.
PubMed 23956241Kahalley LS, Peterson R, Ris MD, Janzen L, Okcu MF, Grosshans DR, Ramaswamy V, Paulino AC, Hodgson D, Mahajan A, Tsang DS, Laperriere N, Whitehead WE, Dauser RC, Taylor MD, Conklin HM, Chintagumpala M, Bouffet E, Mabbott D. Superior Intellectual Outcomes After Proton Radiotherapy Compared With Photon Radiotherapy for Pediatric Medulloblastoma. J Clin Oncol. 2020 Feb 10;38(5):454-461. doi: 10.1200/JCO.19.01706. Epub 2019 Nov 27.
PubMed 31774710Salloum R, Chen Y, Yasui Y, Packer R, Leisenring W, Wells E, King A, Howell R, Gibson TM, Krull KR, Robison LL, Oeffinger KC, Fouladi M, Armstrong GT. Late Morbidity and Mortality Among Medulloblastoma Survivors Diagnosed Across Three Decades: A Report From the Childhood Cancer Survivor Study. J Clin Oncol. 2019 Mar 20;37(9):731-740. doi: 10.1200/JCO.18.00969. Epub 2019 Feb 7.
PubMed 30730781Ostrom QT, Price M, Neff C, Cioffi G, Waite KA, Kruchko C, Barnholtz-Sloan JS. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2016-2020. Neuro Oncol. 2023 Oct 4;25(12 Suppl 2):iv1-iv99. doi: 10.1093/neuonc/noad149.
PubMed 37793125
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Systemic Biomarkers to Predict Radiation-Induced Neurocognitive Decline in Pediatric and Young Adults With Primary Brain Tumors (BIO-RIN)
- ClinicalTrials.gov ID
- NCT06779487
- Acronym / sponsor ID
- BIO-RIN / 4580
- Conditions
- Brain Tumors, Medulloblastoma, Glioma, Ependymoma
- Keywords
- Brain Tumor, Radiotherapy, Proton Beam Therapy, Neuro-cognition, Bio-markers
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Tata Memorial CentreUniversity, hospital or other
- Study start
- 11 Feb 2025 (actual)
- Primary completion
- Feb 2032 (estimated)
- Study completion
- Feb 2032 (estimated)
- First posted
- 16 Jan 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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 design
- Observational model
- Other
- Time perspective
- Prospective
Who may qualify
- Ages
- 5 to 39 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- 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.
Key inclusion criteria (4 listed)
- Age 5-39 years
- Histological diagnosis of primary brain tumor
- Decision for treatment with radical intent radiotherapy
- Signed assent and parental consent form for pediatric age group and signed consent form for adults.
Key exclusion criteria (3 listed)
- Inability to undergo neurocognitive evaluation
- Palliative radiotherapy.
- Expected life expectancy < 1 year
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2025.
- Results publication: PubMed 32719487Ayoub R, Ruddy RM, Cox E, Oyefiade A, Derkach D, Laughlin S, Ades-Aron B, Shirzadi Z, Fieremans E, MacIntosh BJ, de Medeiros CB, Skocic J, Bouffet E, Miller FD, Morshead CM, Mabbott DJ. Assessment of cognitive and neural recovery in survivors of pediatric brain tumors in a pilot clinical trial using metformin. Nat Med. 2020 Aug;26(8):1285-1294. doi: 10.1038/s41591-020-0985-2. Epub 2020 Jul 27.
- Results publication: PubMed 23956241Brown PD, Pugh S, Laack NN, Wefel JS, Khuntia D, Meyers C, Choucair A, Fox S, Suh JH, Roberge D, Kavadi V, Bentzen SM, Mehta MP, Watkins-Bruner D; Radiation Therapy Oncology Group (RTOG). Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial. Neuro Oncol. 2013 Oct;15(10):1429-37. doi: 10.1093/neuonc/not114. Epub 2013 Aug 16.
- Results publication: PubMed 31774710Kahalley LS, Peterson R, Ris MD, Janzen L, Okcu MF, Grosshans DR, Ramaswamy V, Paulino AC, Hodgson D, Mahajan A, Tsang DS, Laperriere N, Whitehead WE, Dauser RC, Taylor MD, Conklin HM, Chintagumpala M, Bouffet E, Mabbott D. Superior Intellectual Outcomes After Proton Radiotherapy Compared With Photon Radiotherapy for Pediatric Medulloblastoma. J Clin Oncol. 2020 Feb 10;38(5):454-461. doi: 10.1200/JCO.19.01706. Epub 2019 Nov 27.
- Results publication: PubMed 30730781Salloum R, Chen Y, Yasui Y, Packer R, Leisenring W, Wells E, King A, Howell R, Gibson TM, Krull KR, Robison LL, Oeffinger KC, Fouladi M, Armstrong GT. Late Morbidity and Mortality Among Medulloblastoma Survivors Diagnosed Across Three Decades: A Report From the Childhood Cancer Survivor Study. J Clin Oncol. 2019 Mar 20;37(9):731-740. doi: 10.1200/JCO.18.00969. Epub 2019 Feb 7.
- Results publication: PubMed 37793125Ostrom QT, Price M, Neff C, Cioffi G, Waite KA, Kruchko C, Barnholtz-Sloan JS. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2016-2020. Neuro Oncol. 2023 Oct 4;25(12 Suppl 2):iv1-iv99. doi: 10.1093/neuonc/noad149.
- Individual participant dataSharing planned: No. Data will be kept secured with investigators and can be shared as per institutional ethics committee rules and regulations.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Tata Memorial Hospital (TMH) Parel, and Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Kharghar
Mumbai, India
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Brain Tumors and Medulloblastoma, run by Tata Memorial Centre at 1 site in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 11 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Biomarkers associated with radiation-induced neurocognitive decline (time frame: 84 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06779487, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Apr 2025.