Acute Lymphoblastic Leukemia
Conditions
Keywords
Adult survivor of acute lymphoblastic leukemia, Executive dysfunction, Transcranial direct current stimulation, Cancer prevention and control
Brief summary
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
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.
Interventions
DEVICEtranscranial Direct Current Stimulation (tDCS)
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.
DEVICESham
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.
OTHERCognitive Assessment
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.
OTHERBrain Games Stimulation
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.
Sponsors
St. Jude Children's Research Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility of At Home tDCS Intervention | 5 weeks after participant enrollment | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neurocognitive Questionnaire: CCSS-NCQ | Baseline at participant enrollment and 5 week follow-up, results of measurements from both time points were reported in the following table. | 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. |
| NIH Toolbox Card Sort Task | After active and sham interventions administered on day one and day two of the trial | 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. |
| NIH Toolbox Flanker Task | After active and sham interventions administered on day one and day two of the trial | 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. |
| NIH Toolbox Working Memory Function | After active and sham interventions administered on day one and day two of the trial | 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. |
| Digit Span Forward | Baseline at participant enrollment and 5 week follow-up, results of measurements from both time points were reported in the following table. | Digit Span Forward, Longest Digits Forward: 0-9; higher score indicates more digits recalled. Higher scores are better. |
| Verbal Fluency | Baseline at participant enrollment and 5 week follow-up, results of measurements from both time points were reported in the following table. | 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. |
| Oral Trail Making Part A | 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: minimum 0 with no maximum amount of time in seconds to say the given letters and numbers. Higher scores are worse. |
| Oral Trail Making Part B | 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: minimum 0 with no maximum amount of time in seconds to say the given letters and numbers. Higher scores are worse. |
| Digit Span Backward | Baseline at participant enrollment and 5 week follow-up, results of measurements from both time points were reported in the following table. | Digit Span Backward, Longest Digits Backward: 0-8; higher score indicates more digits recalled. Higher scores are better. |
Countries
United States
Participant flow
Recruitment details
Between March 2015 and April 2017, 53 participants were enrolled on study to complete one session of active tDCS and one session of sham tDCS. Participants must complete both to move to the At Home tDCS phase. Twenty participants were excluded due to screening failures.
Pre-assignment details
Participants, care providers, investigator and outcomes assessor had no knowledge of group assignment. During campus visit, participants received tDCS and sham sessions at day1 or day2 with only order changed due to randomization. A participant was considered as a control for him/herself. For At Home tDCS phase, single arm treatment was conducted.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study During campus visit, following randomized design each participant completed tDCS set to sham, tDCS equipment set to active condition, during two consecutive days. Participants who completed the campus visit session and evaluation then were to complete a single arm treatment of 10 stimulation sessions over 5 weeks using a mobile tDCS device twice per week. Within two hours of completing each tDCS session, participants were to complete 20 minutes of cognitive training using a mobile application installed on an iPad. | 31 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Not enough time to complete sessions | 2 |
| Overall Study | Uncomfortable with technology | 1 |
| Overall Study | Unrelated illness | 1 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 38.2 years STANDARD_DEVIATION 9.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 30 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 33 | 0 / 31 | 0 / 28 |
| other Total, other adverse events | 14 / 33 | 10 / 31 | 25 / 28 |
| serious Total, serious adverse events | 0 / 33 | 0 / 31 | 0 / 28 |
Outcome results
Primary
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.
Time frame: 5 weeks after participant enrollment
Population: Participant enrollment for At Home Feasibility of tDCS intervention n=28 Participants Analyzed (Week 5 reported n=25)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| At Home Feasibility of tDCS Intervention | Feasibility of At Home tDCS Intervention | 25 Participants |
Secondary
Digit Span Backward
Digit Span Backward, Longest Digits Backward: 0-8; higher score indicates more digits recalled. Higher scores are better.
Time frame: Baseline at participant enrollment and 5 week follow-up, results of measurements from both time points were reported in the following table.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| At Home Feasibility of tDCS Intervention | Digit Span Backward | 3.7 raw score | Standard Deviation 1 |
| At Home tDCS - Follow-Up | Digit Span Backward | 4.2 raw score | Standard Deviation 1 |
Secondary
Digit Span Forward
Digit Span Forward, Longest Digits Forward: 0-9; higher score indicates more digits recalled. Higher scores are better.
Time frame: Baseline at participant enrollment and 5 week follow-up, results of measurements from both time points were reported in the following table.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| At Home Feasibility of tDCS Intervention | Digit Span Forward | 5.7 raw score | Standard Deviation 1 |
| At Home tDCS - Follow-Up | Digit Span Forward | 5.7 raw score | Standard Deviation 0.9 |
Secondary
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.
Time frame: Baseline at participant enrollment and 5 week follow-up, results of measurements from both time points were reported in the following table.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| At Home Feasibility of tDCS Intervention | Neurocognitive Questionnaire: CCSS-NCQ | Task Efficiency | 17.5 scores on a scale | Standard Deviation 3.3 |
| At Home Feasibility of tDCS Intervention | Neurocognitive Questionnaire: CCSS-NCQ | Memory | 8.1 scores on a scale | Standard Deviation 2.4 |
| At Home Feasibility of tDCS Intervention | Neurocognitive Questionnaire: CCSS-NCQ | Organization | 6.1 scores on a scale | Standard Deviation 1.7 |
| At Home Feasibility of tDCS Intervention | Neurocognitive Questionnaire: CCSS-NCQ | Emotional Regulation | 5.9 scores on a scale | Standard Deviation 2.6 |
| At Home tDCS - Follow-Up | Neurocognitive Questionnaire: CCSS-NCQ | Emotional Regulation | 4.7 scores on a scale | Standard Deviation 1.6 |
| At Home tDCS - Follow-Up | Neurocognitive Questionnaire: CCSS-NCQ | Task Efficiency | 16.2 scores on a scale | Standard Deviation 4 |
| At Home tDCS - Follow-Up | Neurocognitive Questionnaire: CCSS-NCQ | Organization | 5.7 scores on a scale | Standard Deviation 1.6 |
| At Home tDCS - Follow-Up | Neurocognitive Questionnaire: CCSS-NCQ | Memory | 8.3 scores on a scale | Standard Deviation 2 |
Secondary
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.
Time frame: After active and sham interventions administered on day one and day two of the trial
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| At Home Feasibility of tDCS Intervention | NIH Toolbox Card Sort Task | 29.2 scores on a scale | Standard Deviation 0.6 |
| At Home tDCS - Follow-Up | NIH Toolbox Card Sort Task | 29.1 scores on a scale | Standard Deviation 1.4 |
Secondary
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.
Time frame: After active and sham interventions administered on day one and day two of the trial
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| At Home Feasibility of tDCS Intervention | NIH Toolbox Flanker Task | 19.9 scores on a scale | Standard Deviation 0.4 |
| At Home tDCS - Follow-Up | NIH Toolbox Flanker Task | 20.0 scores on a scale | Standard Deviation 0 |
Secondary
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.
Time frame: After active and sham interventions administered on day one and day two of the trial
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| At Home Feasibility of tDCS Intervention | NIH Toolbox Working Memory Function | 17.0 scores on a scale | Standard Deviation 3.2 |
| At Home tDCS - Follow-Up | NIH Toolbox Working Memory Function | 16.8 scores on a scale | Standard Deviation 2.9 |
Secondary
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.
Time frame: Baseline at participant enrollment and 5 week follow-up, results of measurements from both time points were reported in the following table.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| At Home Feasibility of tDCS Intervention | Oral Trail Making Part A | 9.4 seconds | Standard Deviation 2.6 |
| At Home tDCS - Follow-Up | Oral Trail Making Part A | 10.0 seconds | Standard Deviation 6.7 |
Secondary
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.
Time frame: Baseline at participant enrollment and 5 week follow-up, results of measurements from both time points were reported in the following table.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| At Home Feasibility of tDCS Intervention | Oral Trail Making Part B | 53.1 seconds | Standard Deviation 38.9 |
| At Home tDCS - Follow-Up | Oral Trail Making Part B | 47.2 seconds | Standard Deviation 24 |
Secondary
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.
Time frame: Baseline at participant enrollment and 5 week follow-up, results of measurements from both time points were reported in the following table.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| At Home Feasibility of tDCS Intervention | Verbal Fluency | 33.1 raw score | Standard Deviation 11 |
| At Home tDCS - Follow-Up | Verbal Fluency | 34.7 raw score | Standard Deviation 12 |