Cognitive Training and tDCS for Children With FASD

Study Overview
=================
Brief Summary
-----------------
This is a randomized placebo-controlled trial of cognitive training with transcranial direct current stimulation (tDCS) for children and adolescents (ages 10 - 16 years) with prenatal alcohol exposure (PAE).

Detailed Description
-----------------
Prenatal alcohol exposure (PAE) has profound detrimental effects on brain development and, as a result, has permanent consequences for cognition, learning, and behavior. Individuals with Fetal Alcohol Spectrum Disorders (FASD) commonly have a range of neurocognitive impairments that directly lead to practical problems with learning, attention, working memory, task planning/execution, and decision making, among other areas of functioning. Despite the profound public health burden posed by FASD, there have been very few treatment studies in this population. This study will examine the effects of a cognitive remediation training augmented with tDCS in children and adolescents with PAE. Functional magnetic resonance imaging will be collected to provide preliminary data of brain circuitry changes created by this intervention. The study involves a baseline visit with cognitive testing, MRI, 5 sessions of tDCS (including the baseline visit), and a 6th visit for cognitive testing and MRI. All sessions will be completed within a 28 to 56 day time window.

Official Title
-----------------
Neuromodulation Augmented Cognitive Remediation to Improve Executive Dysfunction in Fetal Alcohol Spectrum Disorder (FASD)

Conditions
-----------------
Fetal Alcohol Spectrum Disorders

Intervention / Treatment
-----------------
* Device: Active tDCS
* Behavioral: Cognitive training
* Device: Sham tDCS


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Documented heavy prenatal alcohol exposure (self-report, social service records, or adoption records) and meeting criteria for an associated FASD diagnosis (FAS, partial FAS, or ARND). An available parent or legal guardian capable of giving informed consent Exclusion Criteria: Substance abuse in the participant Neurological condition or other developmental disorder Serious psychiatric disorder known to affect brain functioning and cognitive performance Birthweight < 1500 grams MRI contraindication tDCS contraindication

Ages Eligible for Study
-----------------
Minimum Age: 10 Years
Maximum Age: 16 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 1:1 randomized allocation to active tDCS or placebo (sham tDCS).
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cognitive Training and Active tDCS<br>5 sessions of computerized cognitive training on tasks of attention, concentration, set-shifting, and memory - plus active tDCS (also 5 sessions). | Device: Active tDCS<br>* Active Transcranial Direct Current Stimulation (tDCS) administered with a Neuroelectrics StarStim Enobio cap system (active mode)<br>Behavioral: Cognitive training<br>* BrainHQ Computerized cognitive training<br>|
| Sham Comparator: Cognitive Training and Sham tDCS<br>5 sessions of computerized cognitive training on tasks of attention, concentration, set-shifting, and memory - plus sham tDCS (also 5 sessions) which consists of placebo stimulation with tDCS (ramp-up, but no actual stimulation). | Behavioral: Cognitive training<br>* BrainHQ Computerized cognitive training<br>Device: Sham tDCS<br>* Sham Transcranial Direct Current Stimulation (tDCS) administered with a Neuroelectrics StarStim Enobio cap system (sham mode)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BrainHQ Learning Rate | Participants completed a Divided Attention Task during 5 sessions of tDCS. Unit of measure: milliseconds Meaning: lowest threshold reached across trials / fastest reaction time Direction: lower values represent better performance | Learning rate will be computed over 5 sessions of tDCS spanning 28 to 56 days; Each of the 5 tDCS sessions are 46 minutes long. The divided attention task is administered at the end of each tDCS session. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in D-KEFS Verbal Fluency - Letter | The Delis-Kaplan Executive Function System (D-KEFS) cognitive battery measures executive functioning skills. Task performance is in scaled score points based on items generated and errors (range of 1-19 with a mean of 10 and a standard deviation of 3). Here, we present difference scores between session 1 (baseline) and 5 (completion). Greater values represent more change. Positive values represent improvement; negative values represent decline in performance. | D-KEFS will be administered at baseline and at the final visit (28 to 56 days after baseline) | 
| Change in D-KEFS Verbal Fluency - Category | The Delis-Kaplan Executive Function System (D-KEFS) cognitive battery measures executive functioning skills. Task performance is in scaled score points based on items generated and errors (range of 1-19 with a mean of 10 and a standard deviation of 3). Here, we present difference scores between session 1 (baseline) and 5 (completion). Greater values represent more change. Positive values represent improvement; negative values represent decline in performance. | D-KEFS will be administered at baseline and at the final visit (28 to 56 days after baseline) | 
| Change in D-KEFS Trail-making - Numbers | The Delis-Kaplan Executive Function System (D-KEFS) cognitive battery measures executive functioning skills. Task performance is in scaled score points based on items generated and errors (range of 1-19 with a mean of 10 and a standard deviation of 3). Here, we present difference scores between session 1 (baseline) and 5 (completion). Greater values represent more change. Positive values represent improvement; negative values represent decline in performance. | D-KEFS will be administered at baseline and at the final visit (28 to 56 days after baseline) | 
| Change in D-KEFS Trail-making - Letters | The Delis-Kaplan Executive Function System (D-KEFS) cognitive battery measures executive functioning skills. Task performance is in scaled score points based on items generated and errors (range of 1-19 with a mean of 10 and a standard deviation of 3). Here, we present difference scores between session 1 (baseline) and 5 (completion). Greater values represent more change. Positive values represent improvement; negative values represent decline in performance. | D-KEFS will be administered at baseline and at the final visit (28 to 56 days after baseline) | 
| Change in D-KEFS Trail-making - Combined | The Delis-Kaplan Executive Function System (D-KEFS) cognitive battery measures executive functioning skills. Task performance is in scaled score points based on items generated and errors (range of 1-19 with a mean of 10 and a standard deviation of 3). Here, we present difference scores between session 1 (baseline) and 5 (completion). Greater values represent more change. Positive values represent improvement; negative values represent decline in performance. | D-KEFS will be administered at baseline and at the final visit (28 to 56 days after baseline) | 
| Delis Rating of Executive Functioning (D-REF) | The Delis Rating of Executive Functioning (D-REF) contains 60 items rated by the parent to measure the child's executive functioning compared to age-peers. Results are calculated as T-scores, which have a mean of 50 and a standard deviation of 10. Here, we present the scores at study completion (visit 5), post-intervention. Greater values reflect greater executive functioning impairment. | D-REF will be administered at baseline and at the final visit (28 to 56 days after baseline). NOTE that baseline scores are listed previously in the appropriate section | 
| Change in Flanker Inhibitory Control and Attention Task | The Flanker Inhibitory Control and Attention Task from the NIH Toolbox measure inhibitory control and attention. Task performance is in T-scores based on correct items and errors (mean of 50 and a standard deviation of 10). Here, we present difference scores between session 1 (baseline) T-score and 5 (completion) T-score. Greater values represents more change. Positive values represent improvement; negative values represent decline in performance. | NIH Toolbox will be administered at baseline and at the final visit (28 to 56 days after baseline) |