Neurocognitive ImpairmentNCT01014195
Risk of Psychopathology and Neurocognitive Impairment in Leukemia Survivors
An observational study of Neurocognitive Impairment and Acute Lymphoblastic Leukemia, run by St. Jude Children's Research Hospital at 1 site in United States.
Trial summary
1. This study will evaluate the association between changes in basic cognitive and behavioral functioning by the end of chemotherapy treatment, and the later development of higher order executive functions in pediatric acute lymphoblastic leukemia (ALL). 2. Read more about this study
- Who is it for?
- Ages 8 years and older
- Conditions the study is for
- Neurocognitive Impairment, Acute Lymphoblastic Leukemia
- What is being tested?
- Neurocognitive and behavioral evaluation
- How many people
- 237 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2010to Oct 2014
- 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 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Children originally enrolled and treated on the SJCRH TOTXV protocol. The study has reviewed TOTXV patient database and has identified 343 patients (189 males and 154 females) who will meet the inclusion criteria (assuming no additional deaths or relapse).
Who may be able to join
- Enrolled on SJCRH TOTXV ALL protocol
- ≥ 5 years post diagnosis of ALL
- ≥ 8.0 years of age at time of follow-up evaluation
Who cannot join
- History of cranial or total-body radiation therapy
- History of bone marrow transplant
- History of relapse
- History of head injury, neurological condition unrelated to ALL treatment, or diagnosis of a genetic disorder associated with neurocognitive impairment (e.g. Down Syndrome)
Trial locations and contacts
1 site in 1 country.
United States1 site
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
About this study
- This study will evaluate the association between changes in basic cognitive and behavioral functioning by the end of chemotherapy treatment, and the later development of higher order executive functions in pediatric acute lymphoblastic leukemia (ALL).
- The association between acute treatment-related changes in brain integrity and subsequent brain maturation in long-term survivors of pediatric ALL will be evaluated.
- The association between patterns of behavioral and executive dysfunction and brain maturation in long-term survivors of pediatric ALL will be examined.
- The association between genetic polymorphisms in key enzyme pathways and higher order brain development in long-term survivors of pediatric ALL will be explored.
- The associations between biologic and behavioral indices of fatigue/sleep and higher order brain development in long-term survivors of pediatric ALL will be explored.
Read the detailed description
Survival rates for pediatric acute lymphoblastic leukemia (ALL) now exceed 80%. With this growing population of long-term survivors comes recognition that a considerable proportion experience one or more significant late effects. For children undergoing central nervous system (CNS) treatment, common late effects include neurocognitive impairment and neurobehavioral problems. Although these problems first manifest as subtle difficulties with attention and processing speed, they can evolve into deficits in higher order brain functions that significantly impact functional skills in a subset of long-term survivors. There currently is no method to accurately identify patients at greatest risk for these long-term behavioral and neurocognitive problems. Through this proposal, this study plans to utilize existing data collected during acute treatment to identify predictors of long-term neurocognitive and brain maturation outcomes. The study also proposes to collect data on attention-deficit/hyperactivity disorder (ADHD) and associated comorbidities, higher order executive functions, and structural and functional brain imaging in survivors who are at least 8 years of age and greater than 5 years from diagnosis.
All patients will undergo a single neurocognitive evaluation focused on assessment of higher order executive functions. Patients will be evaluated during their regularly scheduled annual follow-up visit, when health-related monitoring will also occur. Parents of participants will be asked to complete questionnaires designed to assess the family environment and the impact of cancer diagnosis on family functioning and parent stress.
Brain Imaging: To better demonstrate untoward treatment effects upon cortical brain development, quantitative MR imaging of myelin integrity using diffusion tensor imaging (DTI) and cortical thickness assessment using high resolution volumetric imaging will be utilized. All patients will also be evaluated using functional MRI (fMRI) procedures during resting state and participation in attention and working memory tasks. fMRI and DTI data will be de-identified then analyzed at MD Anderson Cancer Center in Houston, Texas.
- Being tested
- Neurocognitive and behavioral evaluation
- Keywords
- Acute Lymphoblastic Leukemia, Neurocognitive function, ADHD, brain imaging, genetic polymorphisms, Psychopathology and neurocognitive Impairment in Leukemia Survivors
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Attention Deficit Disorder with Hyperactivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Neurocognitive and behavioral evaluationOther
The primary neurocognitive outcome will be performance on measures of cognitive flexibility and cognitive fluency. Functional behavior will be evaluated via the child or adult version of the Behavior Rating Inventory of Executive Function, using parent respondent for each version. The presence of ADHD and common comorbid conditions (i.e. depression, anxiety) will be determined with structured diagnostic interviews. Quality of life will be re-assessed with the PedQL.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Survivors of pediatric leukemia treated on Total Therapy Protocol XV (TOTXV) at St. Jude Children's Research Hospital (SJCRH), who are ≥ 8 years of age and ≥ 5 years from diagnosis.
Intervention: Neurocognitive and behavioral evaluation Receives: Other: Neurocognitive and behavioral evaluation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neurocognitive assessment of attention, processing speed, and executive functions.
Measured: Once, at least 5 years post ALL diagnosis and 2 years off treatment
Secondary outcomes (4)
Quantitative magnetic resonance imaging (MRI) and DTI and functional magnetic resonance imaging (fMRI) of brain structure and function.
Measured: Once, at least 5 years post ALL diagnosis and 2 years off treatment
Family and parental stress as reported by primary caregiver.
Measured: Once, at least 5 years post ALL diagnosis and 2 years off treatment
Associations between genetic polymorphisms in key enzyme pathways and higher order brain development in long-term survivors of pediatric ALL.
Measured: Once, at least 5 years post ALL diagnosis and 2 years off treatment
Associations between fatigue and neurocognitive performance and between sleep problems and neurocognitive performance.
Measured: Once, at least 5 years post ALL diagnosis and 2 years off treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2009 (estimated)
- Study startJan 2010
- Primary completionOct 2014
- Study completionOct 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neurocognitive ImpairmentStudies of the same condition, open and under way.
- More trials run by St. Jude Children's Research HospitalThe 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 only
- Time perspective
- Prospective
- Enrolment
- 237 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Jude Children's Research Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kevin Krull, Ph.D, Principal investigator, St. Jude Children's Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01014195
- Sponsor's protocol ID
- NEULS
- Other IDs
- R01MH085849
- Status last verified
- Jun 2016
- First submitted
- 13 Nov 2009
- Last updated
- 7 Jun 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Cheung YT, Sabin ND, Reddick WE, Bhojwani D, Liu W, Brinkman TM, Glass JO, Hwang SN, Srivastava D, Pui CH, Robison LL, Hudson MM, Krull KR. Leukoencephalopathy and long-term neurobehavioural, neurocognitive, and brain imaging outcomes in survivors of childhood acute lymphoblastic leukaemia treated with chemotherapy: a longitudinal analysis. Lancet Haematol. 2016 Oct;3(10):e456-e466. doi: 10.1016/S2352-3026(16)30110-7. Epub 2016 Sep 14.
PubMed 27658980
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Risk of Psychopathology and Neurocognitive Impairment in Leukemia Survivors
- ClinicalTrials.gov ID
- NCT01014195
- Acronym / sponsor ID
- NEULS
- Keywords
- Acute Lymphoblastic Leukemia, Neurocognitive function, ADHD, brain imaging, genetic polymorphisms, Psychopathology and neurocognitive Impairment in Leukemia Survivors
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 237 participants (actual)
- Lead sponsor
- St. Jude Children's Research HospitalUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH), M.D. Anderson Cancer Center
- Study start
- Jan 2010
- Primary completion
- Oct 2014 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 16 Nov 2009 (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.
- This study will evaluate the association between changes in basic cognitive and behavioral functioning by the end of chemotherapy treatment, and the later development of higher order executive functions in pediatric acute lymphoblastic leukemia (ALL).
- The association between acute treatment-related changes in brain integrity and subsequent brain maturation in long-term survivors of pediatric ALL will be evaluated.
- The association between patterns of behavioral and executive dysfunction and brain maturation in long-term survivors of pediatric ALL will be examined.
- The association between genetic polymorphisms in key enzyme pathways and higher order brain development in long-term survivors of pediatric ALL will be explored.
- The associations between biologic and behavioral indices of fatigue/sleep and higher order brain development in long-term survivors of pediatric ALL will be explored.
Detailed description
Survival rates for pediatric acute lymphoblastic leukemia (ALL) now exceed 80%. With this growing population of long-term survivors comes recognition that a considerable proportion experience one or more significant late effects. For children undergoing central nervous system (CNS) treatment, common late effects include neurocognitive impairment and neurobehavioral problems. Although these problems first manifest as subtle difficulties with attention and processing speed, they can evolve into deficits in higher order brain functions that significantly impact functional skills in a subset of long-term survivors. There currently is no method to accurately identify patients at greatest risk for these long-term behavioral and neurocognitive problems. Through this proposal, this study plans to utilize existing data collected during acute treatment to identify predictors of long-term neurocognitive and brain maturation outcomes. The study also proposes to collect data on attention-deficit/hyperactivity disorder (ADHD) and associated comorbidities, higher order executive functions, and structural and functional brain imaging in survivors who are at least 8 years of age and greater than 5 years from diagnosis.
All patients will undergo a single neurocognitive evaluation focused on assessment of higher order executive functions. Patients will be evaluated during their regularly scheduled annual follow-up visit, when health-related monitoring will also occur. Parents of participants will be asked to complete questionnaires designed to assess the family environment and the impact of cancer diagnosis on family functioning and parent stress.
Brain Imaging: To better demonstrate untoward treatment effects upon cortical brain development, quantitative MR imaging of myelin integrity using diffusion tensor imaging (DTI) and cortical thickness assessment using high resolution volumetric imaging will be utilized. All patients will also be evaluated using functional MRI (fMRI) procedures during resting state and participation in attention and working memory tasks. fMRI and DTI data will be de-identified then analyzed at MD Anderson Cancer Center in Houston, Texas.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Group 1 | – | Other: Neurocognitive and behavioral evaluationSurvivors of pediatric leukemia treated on Total Therapy Protocol XV (TOTXV) at St. Jude Children's Research Hospital (SJCRH), who are ≥ 8 years of age and ≥ 5 years from diagnosis. Intervention: Neurocognitive and behavioral evaluation |
Who may qualify
- Ages
- 8 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Children originally enrolled and treated on the SJCRH TOTXV protocol. The study has reviewed TOTXV patient database and has identified 343 patients (189 males and 154 females) who will meet the inclusion criteria (assuming no additional deaths or relapse).
Key inclusion criteria (3 listed)
- Enrolled on SJCRH TOTXV ALL protocol
- ≥ 5 years post diagnosis of ALL
- ≥ 8.0 years of age at time of follow-up evaluation
Key exclusion criteria (4 listed)
- History of cranial or total-body radiation therapy
- History of bone marrow transplant
- History of relapse
- History of head injury, neurological condition unrelated to ALL treatment, or diagnosis of a genetic disorder associated with neurocognitive impairment (e.g. Down Syndrome)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Neurocognitive and behavioral evaluationThe primary neurocognitive outcome will be performance on measures of cognitive flexibility and cognitive fluency. Functional behavior will be evaluated via the child or adult version of the Behavior Rating Inventory of Executive Function, using parent respondent for each version. The presence of ADHD and common comorbid conditions (i.e. depression, anxiety) will be determined with structured diagnostic interviews. Quality of life will be re-assessed with the PedQL. | Other | Group 1 |
Primary outcome
Neurocognitive assessment of attention, processing speed, and executive functions.
Time frame: Once, at least 5 years post ALL diagnosis and 2 years off treatment
4 secondary outcomes
Quantitative magnetic resonance imaging (MRI) and DTI and functional magnetic resonance imaging (fMRI) of brain structure and function.
Time frame: Once, at least 5 years post ALL diagnosis and 2 years off treatment
Family and parental stress as reported by primary caregiver.
Time frame: Once, at least 5 years post ALL diagnosis and 2 years off treatment
Associations between genetic polymorphisms in key enzyme pathways and higher order brain development in long-term survivors of pediatric ALL.
Time frame: Once, at least 5 years post ALL diagnosis and 2 years off treatment
Associations between fatigue and neurocognitive performance and between sleep problems and neurocognitive performance.
Time frame: Once, at least 5 years post ALL diagnosis and 2 years off treatment
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 7 Jun 2016.
- Derived from this study: PubMed 27658980Cheung YT, Sabin ND, Reddick WE, Bhojwani D, Liu W, Brinkman TM, Glass JO, Hwang SN, Srivastava D, Pui CH, Robison LL, Hudson MM, Krull KR. Leukoencephalopathy and long-term neurobehavioural, neurocognitive, and brain imaging outcomes in survivors of childhood acute lymphoblastic leukaemia treated with chemotherapy: a longitudinal analysis. Lancet Haematol. 2016 Oct;3(10):e456-e466. doi: 10.1016/S2352-3026(16)30110-7. Epub 2016 Sep 14.
- St. Jude Children's Research HospitalLink provided by the sponsor.
- Clinical Trials Open at St. JudeLink provided by the sponsor.
Related trials for Neurocognitive Impairment
Recruiting
HEARS-NPS: Addressing Hearing Loss as a Common Unmet Contributor of Neuropsychiatric Symptoms
Alzheimer Disease, Dementia
RecruitingPhase 1
PET Imaging of Phosphodiesterase-4 (PDE4) in Volunteers With Alzheimer Disease (AD) or Mild Cognitive Impairment (MCI)
Alzheimer s Disease, Mild Cognitive Impairment
RecruitingObservational study
Community-based Screening for Alzheimer's Disease
Alzheimer's Disease(AD), Mild Cognitive Impairment (MCI)
RecruitingObservational study
InRAD Observational Study
Alzheimer's Disease(AD), Mild Cognitive Impairment (MCI)
Recruiting
Treating Insomnia in Mild Cognitive Impairment
Mild Cognitive Impairment (MCI), Insomnia
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.
Kevin Krull, Ph.D principal investigator
St. Jude Children's Research Hospital
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 Neurocognitive Impairment and Acute Lymphoblastic Leukemia, run by St. Jude Children's Research Hospital at 1 site in United States.
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 3 inclusion and 4 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 7 Jun 2016. 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 United States. 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?
Neurocognitive assessment of attention, processing speed, and executive functions. (time frame: Once, at least 5 years post ALL diagnosis and 2 years off treatment). 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 NCT01014195, which also lists 1 linked publication.
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 7 Jun 2016.