Treatment for Executive Dysfunction in Adult Survivors of Childhood Acute Lymphoblastic Leukemia

Study Overview
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Brief Summary
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A common and potentially debilitating late effect of childhood cancer treatment is neurocognitive impairment, frequently in the domain of executive dysfunction, which can limit educational attainment, employment, and quality of life. Among the survivors of childhood acute lymphoblastic leukemia (ALL) in the SJLIFE cohort, the frequency of executive function impairment has been shown as high as 58.8%, with moderate to severe impairment as high as 33.5%, and risk for impairment increased with time from diagnosis. Given the potential of pervasive impact of neurocognitive impairment on daily life, interventions directed at reducing neurocognitive dysfunction among childhood cancer survivors with long-term follow-up are needed. This study examines the potential feasibility and efficacy of a novel intervention to improve executive function. Primary Objectives: To evaluate the feasibility of a home-based intervention using Transcranial Direct Current Stimulation (tDCS) and cognitive training in adult survivors of childhood ALL participating in the SJLIFE protocol at St. Jude Children's Research Hospital (SJCRH). Secondary Objectives: To estimate the efficacy of a tDCS intervention paired with cognitive training. To explore the short-term effect of tDCS on measures of executive function among adult survivors of childhood ALL participating in the SJLIFE protocol

Detailed Description
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tDCS is a form of non-invasive brain stimulation and is a potentially useful tool to enhance cognitive function. This study uses an at-home intervention of tDCS and cognitive training and examines its potential usefulness at improving executive function in ALL survivors. Investigators will use tDCS to apply a low electrical current to the participant's scalp in the area of the brain associated with fluent and flexible thinking. The current may make that area of the brain work better for a short period of time. During this time, the participant will play computer games designed to train the brain to work more fluently flexibly. Researchers at St. Jude Children's Research Hospital want to see if pairing the electrical stimulation with the brain games at home is a feasible method to improve cognitive abilities in long-term survivors of childhood ALL. In the first part of this study, the short-term effect of tDCS intervention will be evaluated in the clinical setting using a randomized cross-over trial. The survivors will be randomized to receive either the tDCS intervention or Sham on day 1, with the other treatment given on day 2. Neurocognitive testing will be conducted within two hours of completing stimulation each day. In the second part of this study, the feasibility and potential efficacy of self-administration of the tDCS intervention paired with cognitive training will be evaluated over 5 weeks. Research participants will be taught to use the mobile tDCS device and will be provided one to take home. The device will be programmed by the investigators in advance to control the intensity and duration of the stimulation. The research participants will use the device twice per week as directed. Within two hours of completing each tDCS session participants will complete 20 minutes of cognitive training using a mobile app installed on an iPad. Neurocognitive testing will be conducted pre- and post- intervention.

Official Title
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Feasibility and Efficacy of Transcranial Direct Current Stimulation (tDCS) and Cognitive Training for Executive Dysfunction in Adult Survivors of Childhood Acute Lymphoblastic Leukemia

Conditions
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Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Device: transcranial Direct Current Stimulation (tDCS)
* Device: Sham
* Other: Cognitive Assessment
* Other: Brain Games Stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Current St. Jude LIFE (SJLIFE) Protocol Participant Long term survivor of acute lymphoblastic leukemia (ALL) Currently ≥ 18 years of age Wi-Fi internet access at home History of executive dysfunction, documented by neurocognitive testing, and defined as having an age-adjusted standard score <20th percentile on Trail Making Test Part B, Verbal Fluency, or Digit Span Backward. History of self-reported executive dysfunction in daily life, defined as having a standardized score <20th percentile on BRIEF Initiate, Shift, or Working Memory domains OR having scored <20th percentile on the Childhood Cancer Survivor Study Neurocognitive Questionnaire Task Efficiency or Memory domains. Participant is able to speak and understand the English language. Exclusion Criteria: Any survivor with full scale intelligence quotient (IQ) <80 Currently on stimulants or other medications intended to treat cognitive impairment History of seizures No implanted medical devices or implanted metal in the head Currently pregnant or planning to become pregnant. Inability or unwillingness of research participant or legal guardian/representative to give written informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: tDCS on Day 1<br>On day one, participants will be randomized to receive the transcranial Direct Current Stimulation (tDCS) intervention. On day two, participants receive sham intervention. On both days 1 and 2, within two hours of completing the intervention, participants will complete cognitive assessment. In the second phase of the trial, participants will be evaluated over 5 weeks using a mobile tDCS device and Brain Games Stimulation twice per week. Within two hours of completing each tDCS session, participants will complete 20 minutes of cognitive training using a mobile application installed on an iPad. Cognitive assessment will be conducted pre- and post-intervention using remote assessment. | Device: transcranial Direct Current Stimulation (tDCS)<br>* transcranial Direct Current Stimulation (tDCS) involves modulation of cerebral cortex excitability by the application of weak direct current to the scalp. tDCS is a technique that applies safe, low level direct current through large pads on the scalp to stimulate the underlying brain region, with current level < 0.10 C/cm2. Direct current is transferred by a pair of saline-soaked sponges from the anode to the cathode.<br>* Other names: Soterix Medical Device 1x1-CT;Device: Sham<br>* The sham intervention will be used in both arms with one arm receiving the sham intervention on day 1 and the other receiving the sham intervention on day 2. The sham procedure provides the same small current during ramp up to imitate the intervention, but the current is discontinued after ramp up and no intervention is provided. Direct current is transferred by a pair of saline-soaked sponges from the anode to the cathode.<br>* Other names: placebo;Other: Cognitive Assessment<br>* Three tests will be used to evaluate cognitive function: Dimensional Change Card Sort Test, Flanker Inhibitory Control and Attention Test, and List Sorting Working Memory Test. These measures have a computerized format and are nationally standardized. The Gray Oral Reading Test measures reading comprehension. Participants are asked to read a set of passages and recall specific details from the stories. The Woodcock Johnson Understanding Directions measures listening comprehension. Participants listen to a series of complex instructions, then follow the directions by pointing to various objects in a colored picture.<br>* Other names: Woodcock Johnson Understanding Directions;Other: Brain Games Stimulation<br>* Cognitive exercises using the Lumosity Brain Games program will be used simultaneously with the tDCS intervention. Participants will be asked to engage in training for 20 minutes a day, two days per week over 5 weeks. This program involves cognitive exercises designed to enhance executive function and processing speed.<br>* Other names: www.lumosity.com;|
| Active Comparator: tDCS on Day 2<br>On day one, participants will be randomized to receive sham intervention. On day two, participants receive the transcranial Direct Current Stimulation (tDCS) intervention. On both days 1 and 2, within two hours of completing the intervention, participants will complete cognitive assessment. The second phase of the trial will be conducted the same as for participants in the tDCS on Day 1 arm. Participants will be evaluated over 5 weeks using a mobile tDCS device and Brain Games Stimulation twice per week. Within two hours of completing each tDCS session, participants will complete 20 minutes of cognitive training using a mobile application installed on an iPad. Cognitive testing will be conducted pre- and post-intervention using remote assessment. | Device: transcranial Direct Current Stimulation (tDCS)<br>* transcranial Direct Current Stimulation (tDCS) involves modulation of cerebral cortex excitability by the application of weak direct current to the scalp. tDCS is a technique that applies safe, low level direct current through large pads on the scalp to stimulate the underlying brain region, with current level < 0.10 C/cm2. Direct current is transferred by a pair of saline-soaked sponges from the anode to the cathode.<br>* Other names: Soterix Medical Device 1x1-CT;Device: Sham<br>* The sham intervention will be used in both arms with one arm receiving the sham intervention on day 1 and the other receiving the sham intervention on day 2. The sham procedure provides the same small current during ramp up to imitate the intervention, but the current is discontinued after ramp up and no intervention is provided. Direct current is transferred by a pair of saline-soaked sponges from the anode to the cathode.<br>* Other names: placebo;Other: Cognitive Assessment<br>* Three tests will be used to evaluate cognitive function: Dimensional Change Card Sort Test, Flanker Inhibitory Control and Attention Test, and List Sorting Working Memory Test. These measures have a computerized format and are nationally standardized. The Gray Oral Reading Test measures reading comprehension. Participants are asked to read a set of passages and recall specific details from the stories. The Woodcock Johnson Understanding Directions measures listening comprehension. Participants listen to a series of complex instructions, then follow the directions by pointing to various objects in a colored picture.<br>* Other names: Woodcock Johnson Understanding Directions;Other: Brain Games Stimulation<br>* Cognitive exercises using the Lumosity Brain Games program will be used simultaneously with the tDCS intervention. Participants will be asked to engage in training for 20 minutes a day, two days per week over 5 weeks. This program involves cognitive exercises designed to enhance executive function and processing speed.<br>* Other names: www.lumosity.com;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of At Home tDCS Intervention | This outcome measures the feasibility of remote tDCS and cognitive training. The trial will be considered feasible if at least 50% of the survivors are able to complete 5 sessions (tDCS along with cognitive stimulation) successfully out of 10. | 5 weeks after participant enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Digit Span Forward | Digit Span Forward, Longest Digits Forward: 0-9; higher score indicates more digits recalled. Higher scores are better. | Baseline at participant enrollment and 5 week follow-up, results of measurements from both time points were reported in the following table. | 
| Neurocognitive Questionnaire: CCSS-NCQ | The CCSS-NCQ is a 25 item self-report questionnaire to assess cognitive function across multiple domains in cancer survivors. Participant responses range from 1-3 for each item with higher score indicating more problems. Domain scores are created by summing the relevant item scores for each domain. Score ranges: NCQ Task Efficiency: 9-27. NCQ Emotional Regulation: 3-9. NCQ Organization: 3-9. NCQ Memory: 4-12. | Baseline at participant enrollment and 5 week follow-up, results of measurements from both time points were reported in the following table. | 
| NIH Toolbox Card Sort Task | The Card Sort Task measures cognitive flexibility and attention. Pictures are presented varying along two dimensions (e.g., shape and color). Participants must sort the pictures based on a given dimension. Scores range from 0-40 with higher scores indicating better function. | After active and sham interventions administered on day one and day two of the trial | 
| NIH Toolbox Flanker Task | The Flanker Task measures attention and inhibitory control. Participant focuses on a given stimulus while inhibiting attention to stimuli flanking it. Scores range from 0-40 with higher scores indicating better function. | After active and sham interventions administered on day one and day two of the trial | 
| NIH Toolbox Working Memory Function | The Working Memory Task measures working memory. Participant recalls and sequences different visually and orally presented stimuli. Scores range from 0-28 with higher scores indicating better working memory. | After active and sham interventions administered on day one and day two of the trial | 
| Digit Span Backward | Digit Span Backward, Longest Digits Backward: 0-8; higher score indicates more digits recalled. Higher scores are better. | Baseline at participant enrollment and 5 week follow-up, results of measurements from both time points were reported in the following table. | 
| Verbal Fluency | Verbal Fluency: minimum 0 with no maximum; Count of how many words were generated in 60 seconds per letter with three letters used with no top limit. Higher scores are better. | Baseline at participant enrollment and 5 week follow-up, results of measurements from both time points were reported in the following table. | 
| Oral Trail Making Part A | Oral Trail Making Part A: minimum 0 with no maximum amount of time in seconds to say the given letters and numbers. Higher scores are worse. | Baseline at participant enrollment and 5 week follow-up, results of measurements from both time points were reported in the following table. | 
| Oral Trail Making Part B | Oral Trail Making Part B: minimum 0 with no maximum amount of time in seconds to say the given letters and numbers. Higher scores are worse. | Baseline at participant enrollment and 5 week follow-up, results of measurements from both time points were reported in the following table. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adult survivor of acute lymphoblastic leukemia, Executive dysfunction, Transcranial direct current stimulation, Cancer prevention and control