The Cognitive-Behavioral Dysfunctions and the Potential of Neuroplasticity in Brain Tumors Patients During Radiotherapy

NCT05192447 | Unknown

• 2 other identifiers: 2020/37/B/NZ7/01122480821
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

Primary and secondary brain tumors are a constant challenge for the medicine. Tissue sensitivity to ionizing radiation differs and depends on numerous factors and the same dose of radiation may produce different effects in particular structures of the CNS. It can also affect the surrounding healthy tissues and lead to adverse effects like the cognitive or physical function impairment. One of brain structures most sensitive to ionizing radiation is the limbic system, especially the hippocampus, because it is here that the postnatal neurogenesis takes place via neural stem cells, which are a self-renewing population of precursor cells. There have been no studies that would thoroughly examine the impact of different CNS radiation therapy techniques on the cognitive function, potential neuroplasticity markers or blood-brain barrier damage in brain tumor patients with a concomitant use of neurocognitive combination therapies or physical exercise, and their impact on the CNS function. The aim of the study is to assess the impact of selected RT techniques: IMRT, WBRT, and CyberKnife (SRS) on the processes regulating cognitive and physical function in patients with primary (Group III and IV, WHO, 2016) and metastatic CNS tumors. The secondary objective is the analysis of the effect of selected forms of neurorehabilitation on the parameters studied. The study will be a prospective clinical trial conducted in 150 patients. Patient evaluation will be carried out before RT, after RT, during a follow-up visit-3 months after RT, and finally after 6 months. The methods will be used: analysis of the blood-brain barrier permeability markers including exact connection proteins, markers confirming neuroplasticity of the brain, cerebral secretory activity, and onco- and anti-neuronal antibody activity, brain structure analysis (MRI) and volume testing of selected brain structures, and assessment of cognitive and physical function of the patients. The study will be a part of the search trend aiming to explain the mechanism of the formation of cognitive-behavioral disorders in humans based on the most fundamental principles governing information processing in CNS, and the impact of neoplasia and ionizing radiation on selected brain structures and functions. The results of the study might become a starting point for the formulation of new guidelines on the level of physical activity or cognitive exercise in patients treated with CNS radiation therapy.

Conditions

Brain Tumors; Radiotherapy

Keywords

neuroplasticity; rehabilitation

Outcome Measures

Primary Outcomes (3)

• Markers of BBB disruption

  The astrocytic protein S-100β will be estimated using enzyme-linked immunoassay (ELISA).

  up to 48 months

• Circulating tight junction-related proteins

  To estimate circulating tight junction-related proteins (OCLN, CLDN5, ZO-1) concentrations, rabbit anti - human OCLN antibodies will be used.

  up to 48 months

• Onkoneural antibodies in blood

  Onconeural antibodies will be identified with indirect immunofluorescence and confirmed with Line blott with the use of recombinants.

  up to 48 months

Secondary Outcomes (3)

• Anti-neural antibodies in blood

  up to 48 months

• Superficial anti-neuronal antibodies in blood

  up to 48 months

• MRI scans and the selected structures of the brain

  up to 48 months

Other Outcomes (2)

• Neuropsychological Assessment

  up to 48 months

• Functional Assessment

  up to 48 months

Study Arms (2)

Intervention Group = Exercise Group

EXPERIMENTAL

EG will perform complementary cognitive and physical training (120 min./5/per week during study observation)

Behavioral: Exercise treatment

Control Group

NO INTERVENTION

CG will be provided with normal hospital care during RT and next will conduct a normal daily activity at home.

Interventions

Exercise treatment BEHAVIORAL

Patients selected to EG will carry out complementary cognitive and physical training under supervision of rehabilitation staff. For neuropsychological exercises, the investigators will use the RehaCom system - high quality scientific neurocognitive disorder therapy programs and software. (Time: 30 min./5 times/week per patient during RT). In this time, EG patients will do physical training (such as cycling, running on properly calibrated equipment for the circulatory system parameter measurement (1hour/ 5 days/ week), and neuromuscular and cognitive reeducation exercises using a technically advanced tool - Neuroforma computer software - 30 min/ 5 times/ week). After the end of RT, patients in EG will do a special exercise training at home under supervision of staff from the Department of Rehabilitation, and cognitive training using special tasks (3 times an hour/per week) at home, and two times/week using RehaCom and Neuroforma (60 min/sesion) in our cancer ceter.

Also known as: Rehabilitation treatment

Intervention Group = Exercise Group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with three different CNS groups of tumors: from III and IV brain tumor groups, and metastatic tumors enrolled to RT,
• Age between 18-70 years,
• good general health conditions (according to Eastern Cooperative Oncology Group (ECOG) 0-2),
• obtaining informed consent for participation in the study.

You may not qualify if:

• Patients with numerous tumors (above two),
• psychological or psychiatric illnesses treated pharmacologically,
• neurological disorders (e.g. MS, Parkinson's disease, meningitis, etc.),
• significant clinical circulatory failure (above III NYHA).

Sponsors & Collaborators

• The Greater Poland Cancer Centre: lead
• National Science Centre, Poland: collaborator

Study Sites (1)

Greater Poland Cancer Centre

Poznan, Greater Poland Voivodeship, 61-866, Poland

RECRUITING

Related Publications (18)

• Attia A, Page BR, Lesser GJ, Chan M. Treatment of radiation-induced cognitive decline. Curr Treat Options Oncol. 2014 Dec;15(4):539-50. doi: 10.1007/s11864-014-0307-3.

  PMID: 25228143 BACKGROUND

• Baillieux H, De Smet HJ, Paquier PF, De Deyn PP, Marien P. Cerebellar neurocognition: insights into the bottom of the brain. Clin Neurol Neurosurg. 2008 Sep;110(8):763-73. doi: 10.1016/j.clineuro.2008.05.013. Epub 2008 Jul 7.

  PMID: 18602745 BACKGROUND

• Benraiss A, Chmielnicki E, Lerner K, Roh D, Goldman SA. Adenoviral brain-derived neurotrophic factor induces both neostriatal and olfactory neuronal recruitment from endogenous progenitor cells in the adult forebrain. J Neurosci. 2001 Sep 1;21(17):6718-31. doi: 10.1523/JNEUROSCI.21-17-06718.2001.

  PMID: 11517261 BACKGROUND

• Blyth BJ, Farhavar A, Gee C, Hawthorn B, He H, Nayak A, Stocklein V, Bazarian JJ. Validation of serum markers for blood-brain barrier disruption in traumatic brain injury. J Neurotrauma. 2009 Sep;26(9):1497-1507. doi: 10.1089/neu.2008.0738.

  PMID: 19257803 BACKGROUND

• Fischl B. FreeSurfer. Neuroimage. 2012 Aug 15;62(2):774-81. doi: 10.1016/j.neuroimage.2012.01.021. Epub 2012 Jan 10.

  PMID: 22248573 BACKGROUND

• Greene-Schloesser D, Moore E, Robbins ME. Molecular pathways: radiation-induced cognitive impairment. Clin Cancer Res. 2013 May 1;19(9):2294-300. doi: 10.1158/1078-0432.CCR-11-2903. Epub 2013 Feb 6.

  PMID: 23388505 BACKGROUND

• Hipkiss AR, Cartwright SP, Bromley C, Gross SR, Bill RM. Carnosine: can understanding its actions on energy metabolism and protein homeostasis inform its therapeutic potential? Chem Cent J. 2013 Feb 25;7(1):38. doi: 10.1186/1752-153X-7-38.

  PMID: 23442334 BACKGROUND

• Kanner AA, Marchi N, Fazio V, Mayberg MR, Koltz MT, Siomin V, Stevens GH, Masaryk T, Aumayr B, Vogelbaum MA, Barnett GH, Janigro D. Serum S100beta: a noninvasive marker of blood-brain barrier function and brain lesions. Cancer. 2003 Jun 1;97(11):2806-13. doi: 10.1002/cncr.11409.

  PMID: 12767094 BACKGROUND

• Louis DN, et al. (2016) WHO classification of tumours of the central nervous system, ed 4 Lyon, IARC Press

  BACKGROUND

• Manda K, Ueno M, Anzai K. Cranial irradiation-induced inhibition of neurogenesis in hippocampal dentate gyrus of adult mice: attenuation by melatonin pretreatment. J Pineal Res. 2009 Jan;46(1):71-8. doi: 10.1111/j.1600-079X.2008.00632.x. Epub 2008 Sep 16.

  PMID: 18798786 BACKGROUND

• McDuff SG, Taich ZJ, Lawson JD, Sanghvi P, Wong ET, Barker FG 2nd, Hochberg FH, Loeffler JS, Warnke PC, Murphy KT, Mundt AJ, Carter BS, McDonald CR, Chen CC. Neurocognitive assessment following whole brain radiation therapy and radiosurgery for patients with cerebral metastases. J Neurol Neurosurg Psychiatry. 2013 Dec;84(12):1384-91. doi: 10.1136/jnnp-2013-305166. Epub 2013 May 28.

  PMID: 23715918 BACKGROUND

• Ming GL, Song H. Adult neurogenesis in the mammalian brain: significant answers and significant questions. Neuron. 2011 May 26;70(4):687-702. doi: 10.1016/j.neuron.2011.05.001.

  PMID: 21609825 BACKGROUND

• Mizumatsu S, Monje ML, Morhardt DR, Rola R, Palmer TD, Fike JR. Extreme sensitivity of adult neurogenesis to low doses of X-irradiation. Cancer Res. 2003 Jul 15;63(14):4021-7.

  PMID: 12874001 BACKGROUND

• Schulzke JD, Fromm M. Tight junctions: molecular structure meets function. Ann N Y Acad Sci. 2009 May;1165:1-6. doi: 10.1111/j.1749-6632.2009.04925.x.

  PMID: 19538280 BACKGROUND

• Sun YX, Chu GL (2010) Expression changes of tight junction proteins ZO-1 and occludin after hypoxic-ischemic brain damage in neonatal rats. Zhongguo Xiandai Yixue Zazhi. 20(21):3210-3213

  BACKGROUND

• Wen PY, Chang SM, Van den Bent MJ, Vogelbaum MA, Macdonald DR, Lee EQ. Response Assessment in Neuro-Oncology Clinical Trials. J Clin Oncol. 2017 Jul 20;35(21):2439-2449. doi: 10.1200/JCO.2017.72.7511. Epub 2017 Jun 22.

  PMID: 28640707 BACKGROUND

• Wu PH, Coultrap S, Pinnix C, Davies KD, Tailor R, Ang KK, Browning MD, Grosshans DR. Radiation induces acute alterations in neuronal function. PLoS One. 2012;7(5):e37677. doi: 10.1371/journal.pone.0037677. Epub 2012 May 25.

  PMID: 22662188 BACKGROUND

• Voss MW, Prakash RS, Erickson KI, Basak C, Chaddock L, Kim JS, Alves H, Heo S, Szabo AN, White SM, Wojcicki TR, Mailey EL, Gothe N, Olson EA, McAuley E, Kramer AF. Plasticity of brain networks in a randomized intervention trial of exercise training in older adults. Front Aging Neurosci. 2010 Aug 26;2:32. doi: 10.3389/fnagi.2010.00032. eCollection 2010.

  PMID: 20890449 BACKGROUND

MeSH Terms

Conditions

Brain Neoplasms

Interventions

Rehabilitation

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Health Services; Health Care Facilities Workforce and Services

Study Officials

• Katarzyna Hojan, MD, PhD

  Greater Poland Cancer Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Katarzyna Hojan, MD, PhD

CONTACT

+48601509967; katarzyna.hojan@wco.pl

Ewa Tańska, PhD

CONTACT

+48618850767; ewa.tanska@wco.pl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2021
• First Posted: January 14, 2022
• Study Start: April 1, 2021
• Primary Completion: March 31, 2025
• Study Completion: March 31, 2025
• Last Updated: January 3, 2024

Record last verified: 2023-12

Locations

PL (1)