N-PhenoGENICS: Neurocognitive-Phenome, Genome, Epigenome and Nutriome In Childhood Leukemia Survivors

NCT01913093 | Completed

• 1 other identifier: 1000033923
• Study Type: observational
• Target: 204
• Locations: 1 country
• Sites: 1

Brief Summary

To find possible therapeutic targets to help prevent long-term brain and behavioural side effects in survivors of childhood leukemia that may have been caused by chemotherapy (Treatment-Related late Adverse Neuro-Cognitive Effects: TRANCE). The study hypothesis is that genetic variations of the elements in the folate-related cycles and methotrexate disposition networks are associated with the deficit phenotype (TRANCE) of childhood leukemia survivors.

Conditions

Childhood Leukemia Survivors

Keywords

Childhood leukemia survivors; Acute lymphoblastic leukemia; Leukemia; Late effects; Folate; Blood folate; Neurotoxicity; Methotrexate; Pharmacogenetics; Cognitive; Cognitive late effects; N-PhenoGENICS

Outcome Measures

Primary Outcomes (4)

• DIVERGET

  This is a short battery of tests that has been shown to be predictive of both global and academic impairment in survivors of childhood cancer. All neuro-cognitive tests are done on a same day.

  Within 6 months from the enrolment

• Stop Signal Task (SST)

  Response inhibition, disturbed by behavioral inattention, will be characterized using our task-based computer program, the Stop Signal Task (SST). All neuro-cognitive tests are done on a same day.

  Within 6 months from the enrolment

• CONNERS 3

  To characterize behavioural aspects, we will administer the standard measure based on parent report. All neuro-cognitive tests are done on a same day.

  Within 6 months from the enrolment

• Pathway-based gene variant status

  In the hypothesis-driven genome-wide approach, we will focus on the candidate pathways/regions including (but not limited to): a) Folate/methionine cycle genes and transporters; b) drug metabolizing enzymes and transporters (including families of CYP, SLC and ABC transporters); c) epigenetic modifying factors; and d) neuro-regeneration and tissue repair.

  Within 3 months from the end of enrolment

Secondary Outcomes (8)

• WISC-IV

  Within 6 months from the enrolment

• WIAT-III numerical operations and math fluency composite score

  Within 6 months from the enrolment

• Brief Rating Inventory of Executive Function (BRIEF)

  Within 6 months from the enrolment

• N-Back Task

  Within 6 months from the enrolment

• Folate, vitamin B12 and iron intake

  Within 6 months from the enrolment

Other Outcomes (1)

• Epigenetics marker

  Within 3 months from the end of enrolment

Study Arms (2)

Leukemia survivors with neurocognitive deficit

Leukemia survivors with neuro-cognitive deficit phenotype. Based on DIVERGET and other phenotyping tools, we will identify those with the deficit phenotype. This will be treated as "case".

Leukemia survivors without neurocognitive deficit

Leukemia survivors who did not show impaired neurocognitive function, compared to the Control group defined above.

Eligibility Criteria

• Age: 8 Years - 20 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Childhood leukemia survivors

You may qualify if:

• Past diagnosis of acute lymphoblastic leukemia
• years : 0 months - 20 years : 11 months old at the time of their study visit
• At least 2 years : 0 months from the last treatment for acute lymphoblastic leukemia at the time of their study visit
• Continuous complete remission and undergone no bone marrow transplantation or cranial radiation therapy
• Fluent in English (a subject and one parent) for test completion
• Signed informed consent

You may not qualify if:

• Inability to complete the phenotyping tests
• Down Syndrome diagnosis

Sponsors & Collaborators

• The Hospital for Sick Children: lead
• Canadian Institutes of Health Research (CIHR): collaborator
• Canadian Cancer Society (CCS): collaborator
• C17 Council: collaborator
• Garron Family Cancer Centre: collaborator
• Pediatric Oncology Group of Ontario: collaborator

Study Sites (1)

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Biospecimen

Retention: SAMPLES WITH DNA

DNA samples obtained via blood, saliva and buccal sample collection.

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia; Neurotoxicity Syndromes

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Nervous System Diseases; Poisoning; Chemically-Induced Disorders

Study Officials

• Dr. Shinya Ito, MD

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

• Dr. Sharon Guger

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

• Dr. Johann Hitzler

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

• Dr. Deborah L O'Connor

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

• Dr. Russell Schachar

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

• Dr. Brenda Spiegler

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

• Dr. Rosanna Weksberg

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Division Head, Clinical Pharmacology and Toxicology

Study Record Dates

• First Submitted: July 29, 2013
• First Posted: July 31, 2013
• Study Start: July 1, 2013
• Primary Completion: January 1, 2018
• Study Completion: June 1, 2019
• Last Updated: October 8, 2020

Record last verified: 2020-10

Locations

CA (1)