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Neurostimulation In Adult Survivors of Childhood Acute Lymphoblastic Leukemia (ALL)

Primary Purpose

Acute Lymphoblastic Leukemia

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Active tDCS
Sham tDCS
Sponsored by
St. Jude Children's Research Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Acute Lymphoblastic Leukemia focused on measuring Acute Lymphoblastic Leukemia, Neurocognitive impairment, Executive dysfunction, Survivorship

Eligibility Criteria

18 Years - 39 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Completed treatment for acute lymphoblastic leukemia (ALL) at SJCRH < 21 years at diagnosis
  • Enrolled on St. Jude Lifetime Cohort Study
  • ≥ 5 years post-diagnosis of ALL
  • ≥ 2 years post-treatment completion deemed to impact the central nervous system.
  • Currently between 18 and 39 years of age
  • English language proficiency
  • Executive dysfunction defined as having an age-adjusted standard score <16th percentile on Trail Making Test Part B, Controlled Oral Word association Test, or Digit Span Backward
  • Patient-reported executive dysfunction defined as a standard score >84th percentile on the Childhood Cancer Survivor Study Neurocognitive Questionnaire or the Behavior Rating Scale of Executive Function

Exclusion Criteria:

  • Full scale intelligence score <80
  • Currently taking medication intended to treat neurocognitive impairment (e.g. stimulants)
  • Participated in a past trial of neurostimulation
  • Female who is pregnant or breastfeeding
  • History of seizures within the past year
  • Implanted medical devices or metal in the head
  • History of head injury or a neurodevelopmental disorder (i.e. genetic disorder, hypoxic-ischemic encephalopathy) associated with neurocognitive impairment and unrelated to cancer treatment
  • Currently receiving cancer directed therapy

Sites / Locations

  • St. Jude Children's Research Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Active tDCS

Sham tDCS

Arm Description

Remotely delivered active tDCS + cognitive training

Remotely delivered sham tDCS + cognitive training

Outcomes

Primary Outcome Measures

Direct Testing of Executive Function: Change in Working Memory from baseline to 6 months
Digit Span Backward: Digit Span Backward (DSB), from the Digit Span subtest on the WAIS-IV, is a measure of working memory. The number of digits recalled in the longest span is converted to a standard z-score using age-based norms (Mean=0, SD=1).
Direct Testing of Executive Function: Change in Cognitive Flexibility in baseline to 6 months
Trail Making Test Part B (Trails B): This is a timed task that requires a participant to shift his/her attention adaptively and flexibly. Age-based standardized z-scores are calculated (Mean=0, SD=1).
Direct Testing of Executive Function: Change in Verbal Fluency from baseline to 6 months
Controlled Oral Word Association (COWA): This is a task of cognitive/verbal fluency that measures spontaneous production of words beginning with a designated letter or category. Age-based standardized z-scores are calculated (Mean=0, SD=1).

Secondary Outcome Measures

Change in Patient-Reported Symptoms of Executive Functioning from baseline to 6 months
Patient reported symptoms of executive dysfunction will be evaluated via the Childhood Cancer Survivor Study Neurocognitive Questionnaire (CCSS-NCQ). The CCSS-NCQ is a 32-item questionnaire evaluating 4 domains of executive function. Z-scores (M=0, SD=1) are calculated using sibling data from the Childhood Cancer Survivor Study.
Change in Patient-Reported Symptoms of Executive Functioning from baseline to 6 months
Patient reported symptoms of executive dysfunction will be evaluated via the Behavior Rating Inventory for Executive Function - Adult Version (BRIEF-A). The BRIEF-A is a 75-item measure of executive function that provides age- and sex-specific national normative data for nine domains of executive function (T-Score, M=50, SD=10).
Change in Brain Connectivity from baseline to 6 months
White connectivity will be measured via diffusion tensor imaging and resting state fMRI (rsFMRI). The cortex will be parcellated into anatomical regions based on the high-resolution T1-weighted imaging using the FreeSurfer software (http://surfer.nmr.mgh.harvard.edu/). Probabilistic fiber tracking will be performed for individual seed points within the gray matter/white matter surface for each parcellated cortical region to evaluate strength of the connectivity between each individual region and every other region. The current project will focus analyses on the frontostriatal connections from the DLPFC to the striatum. rsfMRI data will be used to construct functional connectomes for each participant at each time point. We will measure several common connectome properties including global and local efficiency. Connectome modularity, degree distribution, and hub characteristics will also be measured.
Change in Regional Brian Activation from baseline to 6 months
Regional brain activation will be assessed using an N-Back Task. This task requires a participant to respond to a presented stimulus only when it is the same as one presented on a trial at a predetermined number prior to the current trial. For this study, we plan to use 1-back and 2-back trials. Improved efficiency will be defined as reduced activation in dorsolateral prefrontal cortex during performance on the N-Back task during the fMRI. Using Statistical Parametric Mapping software (SPM12, Wellcome Trust Centre for Neuroimaging, London), contrast-images from the fixed-effect analysis in each subject will be used for second level random-effect analysis to create group activation maps. These contrasts include pre- v. post-intervention imaging during the N-back task. Participants assigned to active stimulation will then be contrasted to those assigned to sham stimulation.

Full Information

First Posted
June 18, 2019
Last Updated
July 24, 2023
Sponsor
St. Jude Children's Research Hospital
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT04007601
Brief Title
Neurostimulation In Adult Survivors of Childhood Acute Lymphoblastic Leukemia (ALL)
Official Title
Neurostimulation In Adult Survivors of Childhood Acute Lymphoblastic Leukemia (ALL)
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
December 12, 2019 (Actual)
Primary Completion Date
June 21, 2023 (Actual)
Study Completion Date
June 21, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
St. Jude Children's Research Hospital
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

Brief Summary
Long-term survivors of ALL are at-risk for neurocognitive impairment, particularly in the area of executive functioning. Relatively limited research has focused on interventions for improving neurocognitive outcomes in long-term survivors of ALL. A promising technique for cognitive enhancement is Transcranial Direct Current Stimulation (tDCS) which differs from conventional cognitive remediation approaches in that it directly stimulates specific brain regions responsible for cognitive processes and activates functional networks similar to those activated during cognitive training. Primary Objective To evaluate the efficacy of home-based transcranial direct current stimulation (tDCS) paired with remote cognitive training on direct testing of executive function in survivors of ALL. Secondary Objectives To evaluate the efficacy of home-based transcranial direct current stimulation (tDCS) paired with remote cognitive training on patient-reported symptoms of executive dysfunction in survivors of ALL. To examine the effects of home-based tDCS paired with remote cognitive training on patterns of regional brain activation as measured by functional magnetic resonance imaging. To examine the effects of home-based tDCS paired with remote cognitive training on white matter integrity and structure as measured by diffusion tensor imaging.
Detailed Description
Eligible participants will be randomized to receive 1 mA direct current stimulation over the left dorsolateral prefrontal cortex or placebo/sham for 20 minutes. All participants will receive home-based computerized cognitive training. Participants will complete tDCS paired with cognitive training 2 times per week for 6-months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Lymphoblastic Leukemia
Keywords
Acute Lymphoblastic Leukemia, Neurocognitive impairment, Executive dysfunction, Survivorship

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
127 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Active tDCS
Arm Type
Active Comparator
Arm Description
Remotely delivered active tDCS + cognitive training
Arm Title
Sham tDCS
Arm Type
Placebo Comparator
Arm Description
Remotely delivered sham tDCS + cognitive training
Intervention Type
Device
Intervention Name(s)
Active tDCS
Intervention Description
Participants will receive active 1mA direct current stimulation over the left dorsolateral prefrontal cortex for 20 minutes. Cognitive training: Participants will complete 20 minutes of online cognitive training via Lumosity two days per week for a 6-month intervention period.
Intervention Type
Device
Intervention Name(s)
Sham tDCS
Intervention Description
Participants will receive sham (no direct current) stimulation over the left dorsolateral prefrontal cortex for 20 minutes. Cognitive training: Participants will complete 20 minutes of online cognitive training via Lumosity two days per week for a 6-month intervention period.
Primary Outcome Measure Information:
Title
Direct Testing of Executive Function: Change in Working Memory from baseline to 6 months
Description
Digit Span Backward: Digit Span Backward (DSB), from the Digit Span subtest on the WAIS-IV, is a measure of working memory. The number of digits recalled in the longest span is converted to a standard z-score using age-based norms (Mean=0, SD=1).
Time Frame
Baseline & 6-month follow-up
Title
Direct Testing of Executive Function: Change in Cognitive Flexibility in baseline to 6 months
Description
Trail Making Test Part B (Trails B): This is a timed task that requires a participant to shift his/her attention adaptively and flexibly. Age-based standardized z-scores are calculated (Mean=0, SD=1).
Time Frame
Baseline & 6-month follow-up
Title
Direct Testing of Executive Function: Change in Verbal Fluency from baseline to 6 months
Description
Controlled Oral Word Association (COWA): This is a task of cognitive/verbal fluency that measures spontaneous production of words beginning with a designated letter or category. Age-based standardized z-scores are calculated (Mean=0, SD=1).
Time Frame
Baseline & 6-month follow-up
Secondary Outcome Measure Information:
Title
Change in Patient-Reported Symptoms of Executive Functioning from baseline to 6 months
Description
Patient reported symptoms of executive dysfunction will be evaluated via the Childhood Cancer Survivor Study Neurocognitive Questionnaire (CCSS-NCQ). The CCSS-NCQ is a 32-item questionnaire evaluating 4 domains of executive function. Z-scores (M=0, SD=1) are calculated using sibling data from the Childhood Cancer Survivor Study.
Time Frame
Baseline and 6-month follow-up
Title
Change in Patient-Reported Symptoms of Executive Functioning from baseline to 6 months
Description
Patient reported symptoms of executive dysfunction will be evaluated via the Behavior Rating Inventory for Executive Function - Adult Version (BRIEF-A). The BRIEF-A is a 75-item measure of executive function that provides age- and sex-specific national normative data for nine domains of executive function (T-Score, M=50, SD=10).
Time Frame
Baseline and 6-month follow-up
Title
Change in Brain Connectivity from baseline to 6 months
Description
White connectivity will be measured via diffusion tensor imaging and resting state fMRI (rsFMRI). The cortex will be parcellated into anatomical regions based on the high-resolution T1-weighted imaging using the FreeSurfer software (http://surfer.nmr.mgh.harvard.edu/). Probabilistic fiber tracking will be performed for individual seed points within the gray matter/white matter surface for each parcellated cortical region to evaluate strength of the connectivity between each individual region and every other region. The current project will focus analyses on the frontostriatal connections from the DLPFC to the striatum. rsfMRI data will be used to construct functional connectomes for each participant at each time point. We will measure several common connectome properties including global and local efficiency. Connectome modularity, degree distribution, and hub characteristics will also be measured.
Time Frame
Baseline and 6-month follow-up
Title
Change in Regional Brian Activation from baseline to 6 months
Description
Regional brain activation will be assessed using an N-Back Task. This task requires a participant to respond to a presented stimulus only when it is the same as one presented on a trial at a predetermined number prior to the current trial. For this study, we plan to use 1-back and 2-back trials. Improved efficiency will be defined as reduced activation in dorsolateral prefrontal cortex during performance on the N-Back task during the fMRI. Using Statistical Parametric Mapping software (SPM12, Wellcome Trust Centre for Neuroimaging, London), contrast-images from the fixed-effect analysis in each subject will be used for second level random-effect analysis to create group activation maps. These contrasts include pre- v. post-intervention imaging during the N-back task. Participants assigned to active stimulation will then be contrasted to those assigned to sham stimulation.
Time Frame
Baseline and 6-month follow-up

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
39 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Completed treatment for acute lymphoblastic leukemia (ALL) at SJCRH < 21 years at diagnosis Enrolled on St. Jude Lifetime Cohort Study ≥ 5 years post-diagnosis of ALL ≥ 2 years post-treatment completion deemed to impact the central nervous system. Currently between 18 and 39 years of age English language proficiency Executive dysfunction defined as having an age-adjusted standard score <16th percentile on Trail Making Test Part B, Controlled Oral Word association Test, or Digit Span Backward Patient-reported executive dysfunction defined as a standard score >84th percentile on the Childhood Cancer Survivor Study Neurocognitive Questionnaire or the Behavior Rating Scale of Executive Function Exclusion Criteria: Full scale intelligence score <80 Currently taking medication intended to treat neurocognitive impairment (e.g. stimulants) Participated in a past trial of neurostimulation Female who is pregnant or breastfeeding History of seizures within the past year Implanted medical devices or metal in the head History of head injury or a neurodevelopmental disorder (i.e. genetic disorder, hypoxic-ischemic encephalopathy) associated with neurocognitive impairment and unrelated to cancer treatment Currently receiving cancer directed therapy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tara Brinkman, PhD
Organizational Affiliation
St. Jude Children's Research Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
St. Jude Children's Research Hospital
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.stjude.org
Description
St. Jude Children's Research Hospital
URL
http://www.stjude.org/protocols
Description
Clinical Trials Open at St. Jude

Learn more about this trial

Neurostimulation In Adult Survivors of Childhood Acute Lymphoblastic Leukemia (ALL)

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