The Neuro-protective Effects of Exercise in Children With Brain Tumors

The Neuro-protective Effects of Exercise in Children Treated With Cranial Radiation for Brain Tumors

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.

Study Overview

• Status: Completed
• Conditions: Brain Tumor
• Intervention / Treatment: Behavioral: Exercise Program

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.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • The Hospital for Sick Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exercise Training; The 16 participants in this group will be quasi-randomized based on the order of recruitment to start the 12 week exercise intervention without delay (immediate condition).	Behavioral: Exercise Program; Designed to improve cardio-respiratory fitness, the exercise program will be conducted for 12 weeks at a frequency of 3-4 sessions per week. Each exercise session will be conducted after school for a total duration of 90 minutes (group sessions) or 30 minutes (home-based sessions). Group session activities will include i) warm-up (i.e. walk/jog, games) [10 mins], ii) aerobic training/fitness games [30 mins], iii) organized sports [30 mins], iv) cool down (i.e. stretching, low intensity games) [10 mins] and v) snack and reward (15 mins). Participants in the Group setting had three 90-minute group sessions per week. Participants in the Combined setting had two 90-minute group sessions and two 30-minute individual home-based sessions per week.
Experimental: Delayed Exercise Training; The 16 participants in this group will be quasi-randomized based on the order of recruitment to start the 12 week exercise intervention after a 12 week no exercise training period (delayed condition).	Behavioral: Exercise Program; Designed to improve cardio-respiratory fitness, the exercise program will be conducted for 12 weeks at a frequency of 3-4 sessions per week. Each exercise session will be conducted after school for a total duration of 90 minutes (group sessions) or 30 minutes (home-based sessions). Group session activities will include i) warm-up (i.e. walk/jog, games) [10 mins], ii) aerobic training/fitness games [30 mins], iii) organized sports [30 mins], iv) cool down (i.e. stretching, low intensity games) [10 mins] and v) snack and reward (15 mins). Participants in the Group setting had three 90-minute group sessions per week. Participants in the Combined setting had two 90-minute group sessions and two 30-minute individual home-based sessions per week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of implementing an excercise intervention	We will look at several factors, including recruitment rate, exercise adherence rate, retention rate and participant/parent satisfaction to determine the feasability of this intervention	At week 42-45

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fitness	Fitness will be measured using the volume of oxygen consumed while exercising at maximum capacity (VO2max) on a stationary bicycle.	Baseline, once at week 26-29 and once at week 42-45
Neuro-cognitive outcome	Three neuro-cognitive processes important for cognitive development, and found to be sensitive to radiation injury, will be assessed. These measures of cognition include attention, information processing speed, and declarative memory.	Baseline, once at week 26-29 and once at week 42-45
Neural recovery (gliogenesis/neurogenesis)	Changes in white matter integrity may occur as a result of gliogenesis and will be measured using Diffusion Tensor Imaging (DTI). Neurogenesis occurs primarily within the hippocampus, a structure important for learning a memory. Cerebral blood flow (CBF) has been demonstrated to be a potential surrogate imaging measure of neurogenesis. As such, we will use Arterial Spin Labeled (ASL) perfusion MRI to obtain estimates of CBF within the hippocampus.	Baseline, once at week 26-29 and once at week 42-45

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: Donald Mabbott, PhD, The Hospital for Sick Children, Toronto Canada

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2011
• Primary Completion (Actual): March 16, 2015
• Study Completion (Actual): March 16, 2015

Study Registration Dates

• First Submitted: August 15, 2013
• First Submitted That Met QC Criteria: September 13, 2013
• First Posted (Estimated): September 18, 2013

Study Record Updates

• Last Update Posted (Actual): July 16, 2025
• Last Update Submitted That Met QC Criteria: July 11, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Exercise; Brain Tumor; Pediatrics; Neuro-radiation
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms; Brain Neoplasms
• Other Study ID Numbers: 1000019124

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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