Clinical trial NCT01944761: The Neuro-protective Effects of Exercise in Children With Brain Tumors
Official title: The Neuro-protective Effects of Exercise in Children Treated With Cranial Radiation for Brain Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Brain Tumor
Keywords: Pediatrics
Brain Tumor
Neuro-radiation
Exercise
Lead sponsor: The Hospital for Sick Children
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2013-09-18
Enrollment: 32
Sex: ALL
Minimum age (years): 7
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The objectives of our proposed study are to (a) evaluate the feasibility of conducting a structured exercise program in children treated with cranial radiation for brain tumors, (b) test whether exercise results in improved thinking skills and emotional function, and (c) examine potential mechanisms of improved outcome, particularly recovery of white matter and grey matter.

Detailed description: Brain tumors are the leading cause of death and disability from childhood disease in developed countries. With treatment advances over the last 25 years, survival rates have improved dramatically. However, survival is often achieved at considerable cost. Cranial radiation is frequently required for effective tumor control, and is associated with significant neuro-toxicity, including white matter damage and cognitive morbidity. In order to achieve the best possible outcome for survivors, and ultimately conquer the long-term consequences of this disease, new interventions must be developed to ameliorate the neuro-toxic effects experienced by children. radiation injury can now be used to guide the development of interventions designed to rescue neural tissue. Furthermore, various new agents and activities with potential to stimulate neuro-recovery are now available. The potential value of exercise for rescuing the brain from neuro-toxic effects, for instance, has recently been reported. Next, neuro-cognitive processes that are particularly sensitive to the effects of cranial radiation have been identified and can serve as behavioral assays to test the effectiveness of these new interventions. Finally, novel neuro-imaging tools are available to perform in vivo evaluations in order to delineate potential mechanisms of neuro-recovery. We intend to integrate these new research findings to develop and evaluate a physical exercise-based intervention targeted at rescuing brain tissue of children with brain tumors from the neuro-toxic impact of cranial radiation.

Eligibility criteria: Inclusion Criteria:

* Survivors will be included if they are between 7 and 17 years of age.
* Survivors will be included if they either declare English as their native language or have had at least two years of schooling in English at the time of their first assessment.
* Survivors must have been diagnosed with a hemispheric or posterior fossa tumor and been treated with cranial spinal radiation.
* Survivors no more than 10 years may have elapsed between diagnosis and time of study.
* Survivors with a shunt will be included in the study, but will need to be identified prior to study on-set to discuss any specific considerations for imaging and physical activity.

Exclusion Criteria:

* are younger than 7 years (the delivery of an intervention program to young children carries challenges that make it difficult to include in an initial feasibility grant) or older than 17 years
* require sedation for MRI imaging
* is claustrophobic
* have severe neurological/motor dysfunction that would preclude safe participation in an exercise program.

Primary outcomes:
measure: Feasibility of implementing an excercise intervention
timeFrame: At week 42-45
Secondary outcomes:
measure: Fitness
timeFrame: Baseline, once at week 26-29 and once at week 42-45
measure: Neuro-cognitive outcome
timeFrame: Baseline, once at week 26-29 and once at week 42-45
measure: Neural recovery (gliogenesis/neurogenesis)
timeFrame: Baseline, once at week 26-29 and once at week 42-45
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
Study officials:
affiliation: The Hospital for Sick Children, Toronto Canada
name: Donald Mabbott, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Szulc-Lerch KU, Timmons BW, Bouffet E, Laughlin S, de Medeiros CB, Skocic J, Lerch JP, Mabbott DJ. Repairing the brain with physical exercise: Cortical thickness and brain volume increases in long-term pediatric brain tumor survivors in response to a structured exercise intervention. Neuroimage Clin. 2018 Mar 5;18:972-985. doi: 10.1016/j.nicl.2018.02.021. eCollection 2018.
citation: Piscione PJ, Bouffet E, Timmons B, Courneya KS, Tetzlaff D, Schneiderman JE, de Medeiros CB, Bartels U, Mabbott DJ. Exercise training improves physical function and fitness in long-term paediatric brain tumour survivors treated with cranial irradiation. Eur J Cancer. 2017 Jul;80:63-72. doi: 10.1016/j.ejca.2017.04.020. Epub 2017 May 25.
citation: Riggs L, Piscione J, Laughlin S, Cunningham T, Timmons BW, Courneya KS, Bartels U, Skocic J, de Medeiros C, Liu F, Persadie N, Scheinemann K, Scantlebury N, Szulc KU, Bouffet E, Mabbott DJ. Exercise training for neural recovery in a restricted sample of pediatric brain tumor survivors: a controlled clinical trial with crossover of training versus no training. Neuro Oncol. 2017 Mar 1;19(3):440-450. doi: 10.1093/neuonc/now177.
citation: Cox E, Bells S, Timmons BW, Laughlin S, Bouffet E, de Medeiros C, Beera K, Harasym D, Mabbott DJ. A controlled clinical crossover trial of exercise training to improve cognition and neural communication in pediatric brain tumor survivors. Clin Neurophysiol. 2020 Jul;131(7):1533-1547. doi: 10.1016/j.clinph.2020.03.027. Epub 2020 Apr 13.