Clinical trial NCT06312969: Technological Gaming in Cancer Survivors (WINNERS)
Official title: Cognitive Training Through Technological Gaming To Ameliorate Cognitive Effects Related To Childhood Cancer Treatment (WINNERS)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Survivors of Childhood Cancer
Keywords: Cancer Survivors
Survivors of Childhood Cancer
Chemotherapy-related Cognitive Impairment
Functional Magnetic Resonance Imaging (fMRI)
Video Games
Exergaming
Lead sponsor: Instituto de Investigación Hospital Universitario La Paz
Sponsor class: OTHER
Collaborators: name: Hospital Ruber Internacional
name: Universidad Rey Juan Carlos
First posted: 2024-03-15
Enrollment: 56
Sex: ALL
Minimum age (years): 8
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized versus control group clinical trial.
Primary purpose: TREATMENT

Brief summary: HYPOTHESIS

1. Neurocognitive deficits in cancer survivors are underestimated. They represent a very limiting long-term side effect in this group of patients.
2. An individualized, planned and limited intervention using technological gaming can improve neurocognitive function in these pediatric patients by taking advantage of the plasticity of the central nervous system (CNS) in the pediatric age.
3. Changes can be demonstrated not only at the cognitive level, but also at the structural and functional level using neuroimaging techniques after our intervention.
4. In addition to the aforementioned benefits, this therapeutic tool can improve some clinical-analytical markers used in the follow-up of cancer survivors, such as immunological markers like lymphocyte populations and inflammatory cytokines.
5. The neurocognitive effects of this therapy are not only produced at the time of the intervention, but remain until months after the intervention.
6. The positive impact of the treatment is not only observed in the patients, but also in the psychological and emotional state of the family members.

VARIABLES

1. Clinically relevant improvement with moderate or large effect size in the following parameters as measured by neuropsychological tests.
2. Statistically significant changes in neuroimaging tests.
3. Statistically significant changes in immune and inflammatory biomarkers before and after treatment.

STUDY DESIGN In this clinical trial, randomized versus control group, unblinded, the aim is to demonstrate the neuropsychological, structural and functional benefit of an intervention using video games in child cancer survivors.

POPULATION OF THE STUDY The target population participating in the study will include patients of either sex aged 8-17 years who completed cancer treatment 1-5 years ago. They must have received treatment with neurotoxic potential: intrathecal/intraventricular chemotherapy, high-dose chemotherapy with crossing of the blood-brain barrier, CNS radiotherapy or hematopoietic stem cell transplantation (HSCT).

Detailed description: BACKGROUND AND RATIONALE Several authors have described specific cognitive damage following cancer treatments (often chemotherapy and radiotherapy), which has been termed "chemo-brain". This condition produces alterations in different neurocognitive fields such as memory, learning, concentration, reasoning, executive functions, attention and visuospatial skills.

In this research project the investigator team propose an intervention aimed at one of the most limiting adverse effects of cancer and its treatment such as neurocognitive deficits through technological game platforms and brain training used in a directed, controlled and supervised manner.

HYPOTHESIS

1. Neurocognitive deficits in cancer survivors are underestimated. They represent a very limiting long-term side effect in this group of patients.
2. An individualized, planned and limited intervention using technological gaming can improve neurocognitive function in these pediatric patients by taking advantage of the plasticity of the central nervous system (CNS) in the pediatric age.
3. Changes can be demonstrated not only at the cognitive level, but also at the structural and functional level using neuroimaging techniques after our intervention.
4. In addition to the aforementioned benefits, this therapeutic tool can improve some clinical-analytical markers used in the follow-up of cancer survivors, such as immunological markers like lymphocyte populations and inflammatory cytokines.
5. The neurocognitive effects of this therapy are not only produced at the time of the intervention, but remain until months after the intervention.
6. The positive impact of the treatment is not only observed in the patients, but also in the psychological and emotional state of the family members.

VARIABLES

1. Clinically relevant improvement with moderate or large effect size in the following parameters as measured by neuropsychological tests: TAVECI/TAVEC, CATA, TONI-4 (form A), Digits, SDMT, ROCF, TFV, Stroop, Vocabulary
2. Statistically significant changes in neuroimaging tests. The following variables will be measured:

   1. Structural imaging: volume measurement and Voxel Based Morphometry
   2. Diffusion Imaging: diffusion maps and structural connectivity
   3. Functional imaging: resting state and task based fMRI
3. Statistically significant changes in immune and inflammatory biomarkers before and after treatment:

   1. Study of lymphocyte populations by parametric flow cytometry: T lymphocytes, B lymphocytes, natural killer (NK) lymphocytes, NK T lymphocytes
   2. Study of inflammatory cytokines by LUMINEX: IL-2, IL-4, IL-6, TNF alpha, IFN gamma, IL-10, IL-17TH, IL-1R antagonist

STUDY DESIGN

In this clinical trial, randomized versus control group, unblinded, the aim is to demonstrate the neuropsychological, structural and functional benefit of an intervention using video games in child cancer survivors, patients will follow the following phases:

* Informed consent
* Recruitment, inclusion and exclusion criteria.
* Initial T0 assessment
* Randomization
* Treatment phase for the intervention group. Waiting phase for control group
* Early post-treatment evaluation T+3
* Late post-treatment evaluation T+6

POPULATION OF THE STUDY The target population participating in the study will include patients of either sex aged 8-17 years who completed cancer treatment 1-5 years ago. They must have received treatment with neurotoxic potential: intrathecal/intraventricular chemotherapy, high-dose chemotherapy with crossing of the blood-brain barrier, CNS radiotherapy or hematopoietic stem cell transplantation (HSCT).

TREATMENT OF THE STUDY Type of intervention

Cognitive training through 3 types of video games:

* "Serious games" or "brain-training games".
* Exer-gaming
* Skill-training games Method of administration

The patient will receive the treatment for a period of 12 weeks, in which they will commit to use the video games of the intervention with the following pattern:

* "Brain-training game": sessions of 7-12 minutes with a frequency of 4 days a week.
* "Exer-gaming": sessions of 15-20 minutes 2 days a week.
* "Skill-training games": sessions of 15-20 minutes 2 days a week.

SAMPLE SIZE It is planned to recruit 56 patients (28 patients for each group, of which 14 will be from the 8-12 years age group and 14 will be from the 13-17 years age group). Recruitment will be for 12 months, with a follow-up period for each patient of 6 months.

Eligibility criteria: Inclusion Criteria:

* Patients between 8 and 17 years of age at the time of recruitment.
* Have completed treatment between 1 and 6 years prior to recruitment.
* Have had one of the following diagnoses:

  * Patients with CNS disease (posterior fossa tumors and supratentorial gliomas smaller than 1 cm affecting associative areas).
  * Patients with hematologic malignancies (leukemia or lymphoma).
  * Patients with solid tumors.
  * Patients with non-malignant hematological diseases and indication for allogeneic hematopoietic progenitor transplantation.
* Having received at least one of the following treatments:

  * Central nervous system surgery.
  * Central nervous system radiotherapy.
  * Intrathecal/intraventricular chemotherapy.
  * Neurotoxic systemic chemotherapy.
  * Hematopoietic stem cell transplantation.
* Informed consent signed by parent/guardian.

Exclusion Criteria:

* Active oncologic disease or relapse of active oncologic disease.
* Prior neurological or psychiatric pathology that may preclude trial or treatment evaluations:

  * Psychological or neurocognitive illness or sequelae that preclude neuropsychological assessment or are expected to significantly artifact MRI results (examples: significant decrease in visual acuity, CNS surgical scar that artifacts imaging results, severe cognitive delay that precludes testing, etc.).
  * Psychological or neurocognitive illnesses or sequelae that prevent or contraindicate the use of video games (epilepsy that prevents the use of screens, significant decrease in visual acuity, etc.).
  * Mild or self-limiting neurological or psychiatric pathology that does not interfere with trial diagnosis and treatment (headache, epilepsy in remission with effective treatment, mild cognitive delay, etc.) will be allowed.
* Current or recent (less than 1 year) use of other cognitive stimulation or brain training that may interfere with study results.
* Refusal to abstain from the use of the study treatment games in case of being assigned to group B (control group).
* Medical treatment that may significantly interfere with neuropsychological, imaging or biomarker assessments.

Primary outcomes:
measure: SDMT Test
timeFrame: Baseline
measure: Change in SDMT Test
timeFrame: At 3 months after recruitment
measure: Change in SDMT Test
timeFrame: At 6 months after recruitment
measure: "DIGITOS" Test
timeFrame: Baseline
measure: Change in "DIGITOS" Test
timeFrame: At 3 months after recruitment
measure: Change in "DIGITOS" Test
timeFrame: At 6 months after recruitment
measure: "TONI-4" test
timeFrame: Baseline
measure: Change in "TONI-4" test
timeFrame: At 3 months after recruitment
measure: Change in "TONI-4" test
timeFrame: At 6 months after recruitment
measure: "ROCF" test
timeFrame: Baseline
measure: Change in "ROCF" test
timeFrame: At 3 months after recruitment
measure: Change in "ROCF" test
timeFrame: At 6 months after recruitment
measure: "TFV" test
timeFrame: Baseline
measure: Change in "TFV" test
timeFrame: At 3 months after recruitment
measure: Change in "TFV" test
timeFrame: At 6 months after recruitment
measure: "STROOP" test
timeFrame: Baseline
measure: Change in "STROOP" test
timeFrame: At 3 months after recruitment
measure: Change in "STROOP" test
timeFrame: At 6 months after recruitment
measure: "TAVECI" test
timeFrame: Baseline
measure: Change in "TAVECI" test
timeFrame: At 3 months after recruitment
measure: Change in "TAVECI" test
timeFrame: At 6 months after recruitment
measure: "CPT3"
timeFrame: Baseline
measure: Change in "CPT3"
timeFrame: At 3 months after recruitment
measure: Change in "CPT3"
timeFrame: At 6 months after recruitment
measure: "BRIEF" survey
timeFrame: Baseline
measure: Change in "BRIEF" survey
timeFrame: At 3 months after recruitment
measure: Change in "BRIEF" survey
timeFrame: At 6 months after recruitment
measure: "BASC" survey
timeFrame: Baseline
measure: Change in "BASC" survey
timeFrame: At 3 months after recruitment
measure: Change in "BASC" survey
timeFrame: At 6 months after recruitment
measure: Statistically significant changes in neuroimaging tests
timeFrame: At 3 months after recruitment
measure: Statistically significant changes in neuroimaging tests
timeFrame: At 6 months after recruitment
measure: Immune and inflammatory biomarkers
timeFrame: Baseline
measure: Statistically significant changes in immune and inflammatory biomarkers
timeFrame: At 3 months after recruitment
measure: Statistically significant changes in immune and inflammatory biomarkers
timeFrame: At 6 months after recruitment
Secondary outcomes:
measure: Prevalence
timeFrame: Baseline
measure: Perception of the family measured by satisfaction survey
timeFrame: Through study completion, 6 months
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Hospital La Paz
Study officials:
affiliation: Hospital la Paz
name: Antonio Pérez-Martínez, PhD
role: PRINCIPAL_INVESTIGATOR
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