Memory Neuroimaging in Children, Adolescents and Young Adults Following Pediatric Cancer

Pediatric Cancer Clinical Trial

— IMPALA  

Official title:

Memory Neuroimaging in Children, Adolescents and Young Adults Following Pediatric Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04324450
• Other study ID #: C19-17
• Status: Recruiting
• Phase: N/A
• Start date: February 12, 2020
• Est. completion date: February 9, 2023

Study information

• Verified date: April 2021
• Source: Institut National de la Santé Et de la Recherche Médicale, France
• Contact: Anne LAPRIE, MD
• Phone: +33(0)562746164
• Email: laprie.anne[@]iuct-oncopole.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Brain tumours are the leading cause of cancer-related death and morbidity in children, adolescents and young adults. The brain is also one of the most sensitive organs to treatments used in pediatric oncology, even for cancers not related to the central nervous system. Therapeutic index is therefore a major issue in pediatric neuro-oncology. The efficacy of the therapy as well as its toxicity are difficult to measure using standard tests. In order to optimize therapies that could have an impact on the brain, and consequently on the quality of life of patients, it becomes crucial to optimize the means of evaluation.

Few studies to date have focused on the various components of memory impacted following treatment of a posterior fossa tumour. However, supra-tentorial structures such as the hippocampus, which have long been described for their role in memory, are either partially irradiated (irradiated in their lower part due to their proximity to the target volume during irradiation of the posterior fossa) or completely irradiated (e.g. included in the prophylactic irradiation of medulloblastoma prior to dose supplementation in the posterior fossa). On the other hand, the cerebellum plays a central role in learning and procedural memory involved in motor and cognitive learning, as it enables automation and procedural retention such as reading (automation of the grapho-phonemic conversion procedure) or arithmetic (mental arithmetic).

IMPALA study is aimed at investigating the impact of different irradiation doses received by children treated with radiotherapy on cognitive functions related to the hippocampus and to the cerebellum.

This exploratory study will thus provide elements enabling a better limitation of radiotherapy doses on regions linked to the development of cognition and memory. The project brings together researchers and clinicians with complementary expertise in oncology, neurology and imaging in both children and adults. This study will also provide a better understanding of the role of the cerebellum in memory and executive functions, and develop a method that can then be used in a prospective longitudinal multicentre form.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: February 9, 2023
• Est. primary completion date: September 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

FOR ALL PARTICIPANTS

• Affiliation to or beneficiary of a social security scheme

• French mother tongue

• Sufficient visual, auditory (hearing aids permitted), speaking and writing skills for proper performance of neuropsychological tests

• Written informed consent of the adult participant, or of the representatives of parental authority, if applicable

FOR IRRADIATED PATIENTS

• Patient treated before 18 years old

• Patient considered cured after irradiation of a brain tumour (complete clinical and iconographic response at 5 years after the end of radiotherapy).

• Patient who has received localized brain irradiation or craniospinal irradiation for a brain tumour whose treatment includes first-line radiotherapy (ependymomas, medulloblastomas, malignant germinal tumours)

• Patient who received 54 or 59.4 Gy in a localized part of the posterior fossa or supra-tentorial brain; or patients who received 54 Gy over all or part of the posterior fossa and prophylactic irradiation of the entire brain

FOR PATIENTS TREATED BY SURGERY AND/OR CHEMOTHERAPY

• Patients resected from a posterior fossa tumour without radiotherapy (i.e., brain tumours whose treatment does not include first-line radiotherapy: low-grade gliomas including pilocytic astrocytomas)

• Patient treated before 18 years old

• Patient considered cured at 5 years after the end of treatment

Exclusion Criteria:

FOR ALL PARTICIPANTS

• Individual under legal protection of adults (judicial safeguard, guardianship, curatorship, institutionalized, or under a mandate for future protection)

• Severe ataxia

• Individual who participated in another research study that included treatment within the previous 3 years

• Individual with a contraindication to MRI (i.e. in particular, cardiac pacemaker or defibrillator carriers, implanted equipment activated by an electrical, magnetic or mechanical system, carriers of haemostatic clips on intracerebral aneurysms, carriers of orthopaedic implants, claustrophobic)

FOR HEALTHY VOLUNTEERS

• Known neurological or psychiatric history

• History of learning disability or neurodevelopmental disorder follow-up

• Patients undergoing psychotropic treatment (methylphenidate, antidepressants, etc.).

Related Conditions & MeSH terms

• Cancer Brain
• Pediatric Cancer

Intervention

Device:
• MRI
The MRI protocol is composed of: T1-weighted anatomical sequences DTI sequences resting functional MRI 3D MR spectroscopic imaging

Behavioral:
• Cognitive assessment
Battery of neuropsychological tests

Locations

Country	Name	City	State
France	ToNIC / UMR1214	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
Institut National de la Santé Et de la Recherche Médicale, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Structural characteristics of declarative memory neuronal substrate: volume of the hippocampus	Volume of the hippocampus obtained from T1-weighted anatomical	Day 1
Primary	Structural characteristics of declarative memory neuronal substrate: cortical thickness of the hippocampus	Cortical thickness of the hippocampus obtained from T1-weighted anatomical	Day 1
Primary	Structural characteristics of declarative memory neuronal substrate: Microstructural integrity of the hippocampus	Microstructural integrity of the hippocampus obtained from Diffusion Tensor Imaging (DTI) sequences used to calculate the fraction of anisotropy and the mean diffusion sequences	Day 1
Primary	Episodic memory performance	Episodic memory performance of the participants in the different groups when evaluating episodic declarative memory, assessed with Children's Memory Scale in participants under 16 years old and with Wechsler Memory Scale MEM-III in participants over 16 years old (Day 2)	Day 2
Secondary	Declarative episodic memory assessment scores	Scores obtained at memory clinical scale for children	Day 2
Secondary	Declarative semantic memory assessment scores	Scores obtained at Wechsler Intelligence Scale for Children	Day 2
Secondary	Procedural memory assessment scores	Scores obtained at Serial Reaction Time Task	Day 2
Secondary	Short-term auditive memory assessment scores	Scores obtained at Wechsler Intelligence Scale for Children	Day 2
Secondary	Short-term visual memory assessment scores	Scores obtained at Wechsler Memory Scale	Day 2
Secondary	Intellectual capacities assessment scores	Scores obtained at Wechsler Intelligence Scale for Children	Day 2
Secondary	Language assessment scores	Scores obtained at Peabody Picture Vocabulary Test	Day 2
Secondary	Motor functions assessment scores	Scores obtained at Purdue Pegboard Test	Day 2
Secondary	Executive functions assessment scores	Scores obtained at TMT A and B, Stroop Test and Wisconsin Card Sorting Test	Day 2
Secondary	Attentional capacities assessment scores	Scores obtained at Test of Attentional Performance 2.3.1	Day 2
Secondary	Cerebellar volume	Cerebellar volume obtained from T1-weighted anatomical sequences	Day 1
Secondary	Micro-structural integrity of the cerebellum	Micro-structural integrity of the cerebellum achieved by using DTI sequences to calculate the fraction of anisotropy and average diffusivity	Day 1
Secondary	Cerebral blood volume obtained from brain perfusion imaging	Cerebral blood volume obtained from brain perfusion imaging	Day 1
Secondary	Post-therapeutic hypoxia	Post-therapeutic hypoxia as measured by magnetic resonance spectrometry of the hippocampus and cerebellum	Day 1
Secondary	Neuronal density	Neuronal density as measured by magnetic resonance spectrometry of the hippocampus and cerebellum	Day 1
Secondary	Functional connectivity index	Functional connectivity index, obtained via resting functional MRI.	Day 1
Secondary	Age at the time of treatment	Age at the time of treatment from the patients' medical records	Day 1
Secondary	Radiotherapy doses	Radiotherapy doses received in the cerebellum, in the hippocampus, and in the whole brain from the patients' medical records	Day 1
Secondary	Cerebellum and hippocampus Normal Tissue Complication Probability	Cerebellum and hippocampus Normal Tissue Complication Probability (NTCP)	Day 1