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

Acute Lymphoblastic Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04007601
• Other study ID #: NEUROSTIM
• Secondary ID: R01CA239630
• Status: Completed
• Phase: N/A
• Start date: December 12, 2019
• Est. completion date: June 21, 2023

Study information

• Verified date: July 2023
• Source: St. Jude Children's Research Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 127
• Est. completion date: June 21, 2023
• Est. primary completion date: June 21, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 39 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Device:
• Active tDCS
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.
• Sham tDCS
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.

Locations

Country	Name	City	State
United States	St. Jude Children's Research Hospital	Memphis	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
St. Jude Children's Research Hospital	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	Baseline & 6-month follow-up
Primary	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).	Baseline & 6-month follow-up
Primary	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).	Baseline & 6-month follow-up
Secondary	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.	Baseline and 6-month follow-up
Secondary	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).	Baseline and 6-month follow-up
Secondary	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.	Baseline and 6-month follow-up
Secondary	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.	Baseline and 6-month follow-up

External Links

•   Clinical Trials Open at St. Jude
•   St. Jude Children's Research Hospital