Childhood Leukemia SurvivorsNPGNCT01913093

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

An observational study of Childhood Leukemia Survivors, run by The Hospital for Sick Children at 1 site in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 8 to 20 years
Conditions the study is for: Childhood Leukemia Survivors
How many people: 204 participants
Where: 1 siteCanada
Study dates: Jul 2013to Jun 2019
Phase: Observational
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 8 to 20 years
All sexes
No healthy volunteers
Child, Adult

Study population: Childhood leukemia survivors

Who may be able to join

Past diagnosis of acute lymphoblastic leukemia
8 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

Who cannot join

Inability to complete the phenotyping tests
Down Syndrome diagnosis

Trial locations and contacts

1 site in 1 country.

Canada1 site

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

Other trials in Canada

About this study

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.

Read the detailed description

Hypothesis Genetic variants of the elements in the folate-related cycles and methotrexate disposition networks are associated with the TRANCE phenotype of childhood leukemia survivors.

Objectives

To identify TRANCE phenotypes of the childhood leukemia survivors.
To characterize the folate and vitamin B12 levels of these children
To identify DNA methylation patterns associated with TRANCE trait in the leukemia survivors
To identify SNPs associated with the TRANCE trait in the leukemia survivors.
To identify the "deficit genotype" associated only with the TRANCE leukemia survivors, but not with general population children who show developmental phenotypes similar to TRANCE: TRANCE-unique deficit variant
To replicate the association between the TRANCE-unique deficit variants and the TRANCE trait in a population of childhood leukemia survivors.
To evaluate the importance of rare genetic variants in the TRANCE trait in the leukemia survivors.

Study design: A case-control study of leukemia survivors

Analyses

Leukemia survivors will be characterized by their status of neurocognitive function, and categorized into the Deficit case and the non-deficit Control case.
They will be also characterized by the following attributes
Pathway-based genetic variant status (folate and PK-related genes)
Folate and vitamin B12 status
Epigenetic markers
Comparative analyses between neuro-cognitiive deficit phenotype (TRANCE) and Control on those parameters

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
Medical subject headings: Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Neurotoxicity Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT01913093
Study group	Role	What they receive
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.

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Within 3 months from the end of enrolment

Secondary outcomes (8)

WISC-IV
In order to confirm validity of DIVERGT in our sample, and provide the data source for future studies, we will include tests of general cognitive function (WISC-IV). All neuro-cognitive tests are done on a same day.
Measured: Within 6 months from the enrolment
WIAT-III numerical operations and math fluency composite score
In order to confirm validity of DIVERGT in our sample, and provide the data source for future studies, we will include tests of general cognitive function: WIAT-III numerical operations and math fluency composite score. All neuro-cognitive tests are done on a same day.
Measured: Within 6 months from the enrolment
Brief Rating Inventory of Executive Function (BRIEF)
In order to confirm validity of DIVERGT in our sample, and provide the data source for future studies, we will administer Brief Rating Inventory of Executive Function (BRIEF), which is designed to assess executive functioning in the home environment. All neuro-cognitive tests are done on a same day.
Measured: Within 6 months from the enrolment
N-Back Task
In order to confirm validity of DIVERGT in our sample, and provide the data source for future studies, we will administer N-Back Task, which is a continuous performance computerized task used to measure aspects of working memory. All neuro-cognitive tests are done on a same day.
Measured: Within 6 months from the enrolment
Folate, vitamin B12 and iron intake
Folate and other vitamin intakes vary among individuals. Folic acid fortification in Canadian food product has changed the Canadian population norm of folate status, virtually eliminating folate deficiency status. However, a large inter-individual variation still remains. We will use a Supplement Questionnaire to capture information on all and any supplements that participants may be currently taking.
Measured: Within 6 months from the enrolment
Folate status
In order to complement the Supplement Questionnaire (above), we will measure the folate concentration in plasma and red blood cells.
Measured: Within 6 months from the enrolment
Serum vitamin B12
Vitamin B12 and folate pathways interact to maintain biochemical homeostasis. To complement the intake assessment (above), we will measure serum vitamin B12.
Measured: Within 6 months from the enrolment
Iron status
Iron status affects cognitive function of children. In addition to the intake assessment (above), we will estimate iron status by measuring hemoglobin and soluble transferrin receptor.
Measured: Within 6 months from the enrolment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2013Jun 2019

First posted31 Jul 2013 (estimated)
Study startJul 2013
Primary completionJan 2018
Study completionJun 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Childhood Leukemia SurvivorsStudies of the same condition, open and under way.
More trials run by The Hospital for Sick ChildrenThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Observational
Observational model: Case-control
Time perspective: Prospective
Enrolment: 204 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01913093
Sponsor's protocol ID: 1000033923
Acronym: NPG
Status last verified: Oct 2020
First submitted: 29 Jul 2013
Last updated: 8 Oct 2020
Results posted: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Childhood Leukemia Survivors trials

Study at a glance

From the registry record, last updated by the sponsor on 8 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: N-PhenoGENICS: Neurocognitive-Phenome, Genome, Epigenome and Nutriome In Childhood Leukemia Survivors
ClinicalTrials.gov ID: NCT01913093
Acronym / sponsor ID: NPG / 1000033923
Conditions: Childhood Leukemia Survivors
Keywords: Childhood leukemia survivors, Acute lymphoblastic leukemia, Leukemia, Late effects, Folate, Blood folate, Neurotoxicity, Methotrexate
Study type: Observational
Recruitment status: Completed
Enrolment: 204 participants (actual)
Lead sponsor: The Hospital for Sick ChildrenUniversity, hospital or other
Collaborators: Canadian Institutes of Health Research (CIHR), Canadian Cancer Society (CCS), C17 Council, Garron Family Cancer Centre, Pediatric Oncology Group of Ontario
Study start: Jul 2013 (actual)
Primary completion: Jan 2018 (actual)
Study completion: Jun 2019 (actual)
First posted: 31 Jul 2013 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Hypothesis Genetic variants of the elements in the folate-related cycles and methotrexate disposition networks are associated with the TRANCE phenotype of childhood leukemia survivors.

Objectives

To identify TRANCE phenotypes of the childhood leukemia survivors.
To characterize the folate and vitamin B12 levels of these children
To identify DNA methylation patterns associated with TRANCE trait in the leukemia survivors
To identify SNPs associated with the TRANCE trait in the leukemia survivors.
To identify the "deficit genotype" associated only with the TRANCE leukemia survivors, but not with general population children who show developmental phenotypes similar to TRANCE: TRANCE-unique deficit variant
To replicate the association between the TRANCE-unique deficit variants and the TRANCE trait in a population of childhood leukemia survivors.
To evaluate the importance of rare genetic variants in the TRANCE trait in the leukemia survivors.

Study design: A case-control study of leukemia survivors

Analyses

Leukemia survivors will be characterized by their status of neurocognitive function, and categorized into the Deficit case and the non-deficit Control case.
They will be also characterized by the following attributes
Pathway-based genetic variant status (folate and PK-related genes)
Folate and vitamin B12 status
Epigenetic markers
Comparative analyses between neuro-cognitiive deficit phenotype (TRANCE) and Control on those parameters

Study design

Observational model: Case-control
Time perspective: Prospective
Number of arms: 2

Arm	Type	Receives
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.

Who may qualify

Ages: 8 to 20 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult
Study population: Childhood leukemia survivors

Key inclusion criteria (6 listed)

Past diagnosis of acute lymphoblastic leukemia
8 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

Key exclusion criteria (2 listed)

Inability to complete the phenotyping tests
Down Syndrome diagnosis

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Primary outcome

DIVERGET
Time frame: Within 6 months from the enrolment
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.
Stop Signal Task (SST)
Time frame: Within 6 months from the enrolment
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.
CONNERS 3
Time frame: Within 6 months from the enrolment
To characterize behavioural aspects, we will administer the standard measure based on parent report. All neuro-cognitive tests are done on a same day.
Pathway-based gene variant status
Time frame: Within 3 months from the end of enrolment
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.

8 secondary outcomes

WISC-IV
Time frame: Within 6 months from the enrolment
WIAT-III numerical operations and math fluency composite score
Time frame: Within 6 months from the enrolment
Brief Rating Inventory of Executive Function (BRIEF)
Time frame: Within 6 months from the enrolment
N-Back Task
Time frame: Within 6 months from the enrolment
Folate, vitamin B12 and iron intake
Time frame: Within 6 months from the enrolment
Folate status
Time frame: Within 6 months from the enrolment
Serum vitamin B12
Time frame: Within 6 months from the enrolment
Iron status
Time frame: Within 6 months from the enrolment

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2020.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Dr. Shinya Ito, MD principal investigator

The Hospital for Sick Children

Dr. Sharon Guger principal investigator

The Hospital for Sick Children

Dr. Johann Hitzler principal investigator

The Hospital for Sick Children

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

An observational study of Childhood Leukemia Survivors, run by The Hospital for Sick Children at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

DIVERGET (time frame: Within 6 months from the enrolment). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01913093.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2020.