Trial Evaluating an Enhanced Physical Activity Intervention to Improve Cognitive Late Effects in Children Treated With Cranial Radiation for Brain Tumors

BACKGROUND:

- Children treated with cranial radiation therapy (CRT) for brain tumors are at high risk
for developing neurocognitive late effects consisting of significant declines in overall
IQ and specific cognitive impairments, particularly in attention, memory, and processing
speed. Academic functioning, daily activities, and quality of life (QOL) also are
impacted, and children often require special educational services.

- Despite adaptations in radiation therapy (delay of radiation, reduced dose, specialized
techniques), cognitive deficits still develop. Interventions targeting cognitive
rehabilitation are limited yet sorely needed.

- A potential and novel intervention for cognitive rehabilitation that has not been
explored in children with cancer involves physical activity (PA). Compelling evidence
from both human and animal studies indicates that PA affects the same brain mechanisms
and cognitive functions damaged by CRT and chemotherapy.

- Previous PA intervention studies in children with cancer have been found to be feasible,
safe, and beneficial to health but have not examined cognition outcomes. Therefore, we
will conduct a randomized controlled trial to evaluate the effects of PA on the
cognitive functioning of children treated with CRT for brain tumors. In addition, we
will enhance the intervention by combining it with Acceptance and Commitment Therapy
(ACT) techniques to maximize participants' motivation to engage in PA.

- The immediate intervention group (the intervention group ) will engage in the enhanced
PA intervention program for the first 12 weeks followed by 12 weeks of PA maintenance on
their own, while the delayed intervention control group (the control group ) will engage
in their usual physical activity for the first 12 weeks followed by the enhanced PA
intervention program for the second 12 weeks.

OBJECTIVES:

-To assess the effects of a 12-week enhanced physical activity (PA) home intervention on
visual memory (CogState One Card Learning Accuracy score) in children treated with CRT for
brain tumors compared to a control group engaged in usual physical activity during the first
12 weeks.

ELIGIBILITY:

- Children ages 8 - 18 years previously diagnosed with a brain tumor in childhood who are
at least 1 year post-completion of CRT and who are not on an active anti-tumor treatment
will be eligible.

- Children should have reported or documented cognitive difficulties in attention,
learning and memory, or processing speed per the child s parent or legal guardian.

DESIGN:

-This is a prospective single-institution trial. Children will be randomized to one of two
groups: Group 1 (n=30): The immediate intervention group (the intervention group ) will
participate in the enhanced PA home intervention group for the first 12 weeks; followed by 12
weeks of PA maintenance on their own.

Group 2 (n=30): The delayed intervention control group (the control group ) will engage in
their usual physical activity (no intervention) for 12 weeks; followed by the enhanced PA
home intervention for 12 weeks.

- Neurobehavioral, circulating growth factors, and cardiorespiratory evaluations will be
conducted at baseline (T0) and after the first 12 weeks at home (T2) in both the
intervention and control groups. The acute effects of the in-lab PA will be assessed
immediately following the baseline treadmill fitness test (T1) using selected cognitive
measures in both groups. PA for both groups will be measured throughout the period at
home via activity monitors.

- After the completion of the first 12 week period at home and the follow-up evaluations
(T2), the intervention group will be asked to maintain their PA levels on their own for
the next 12 weeks while the control group will participate in the enhanced PA
intervention at home for 12 weeks. A final cognitive evaluation will be conducted in
both groups after the completion of the second 12- week period (T3). The primary outcome
measure is the Cogstate One Card Learning Accuracy Score. The effects of PA on other
neurobehavioral outcomes and circulating growth factors also will be examined.

- INCLUSION CRITERIA:

1. Children ages 8 - 18 years of age, diagnosed with brain tumor in childhood.

2. Must be at least 1 year post completion of radiation therapy to the brain or
brain and spine.

3. Must be off anti-neoplastic therapy for at least 2 weeks and all therapy-related
toxicities should return to baseline or less than or equal to Grade 1 if
previously nonexistent.

4. Have parent-reported or documented difficulties in attention, processing speed,
memory, or learning as assessed by the screening questions (a score of at least 3
on any one of the 4 questions or the participant having greater than or equal to
1/2 SD decline in test scores, scores < 85, or special education services or
accommodations).

5. Must have a parent or legal guardian willing to complete the parent proxy
behavioral questionnaires and help their child participate in the study
procedures at home.

6. Ability to read and understand the English language.

7. Have regular access to a computer (either PC or Mac with a built-in USB port).

8. Must be willing to register online and install the software to use an
age-appropriate activity monitor and website which will include sharing some
personal identifiable information, to allow the participant to track their
physical activity.

9. Ability of subject or Legally Authorized Representative (LAR) to understand and
willingness to sign a written informed consent document.

EXCLUSION CRITERIA

1. A child with diffuse intrinsic pontine glioma (DIPG) or recurrent high grade brain
tumors will be excluded due to the poor prognosis, making participation for the length
of this study difficult.

2. Significant medical problems, such as severe uncontrolled illnesses, or physical
impairments that prohibit the child from exercising at moderate to vigorous levels
based on the clinical judgment of the examining physician or nurse practitioner.

3. Currently engaging in > 3 hours of moderate to vigorous physical activity per week, as
reported in the exercise screening questions completed at the pre-study screening
evaluation.

4. Significant cognitive, behavioral, or emotional impairments as judged by an
investigator that would prevent the child from understanding or completing the
intervention or assessment measures.

5. A child has plans to start a new treatment for attention/memory problems in the next 3
months.

6. Currently on or planning to begin active neoplastic therapy, as the side effects may
significantly impair ability to participate in physical activity.

7. Unable to travel to NIH for the evaluations.