Attentional-Control Training for Sickle Cell Disease

(ACT Trial)

Recruiting at 1 trial location

Overseen By Steven J Hardy, Ph.D.

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Children's National Research Institute

Must be taking: Blood transfusions

Disqualifiers: Low IQ, Mental health, Seizures, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 4 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a game-based program called EndeavorRx can improve attention in children with sickle cell disease (SCD). SCD often makes focusing difficult for children, and EndeavorRx aims to train attention skills through engaging activities on a tablet. The trial seeks to determine if children find the program easy to use and if it enhances their attention. Suitable candidates for this trial are children aged 8-16 who have SCD, regularly receive blood transfusions, and face attention challenges. As an unphased trial, this study offers a unique opportunity for children to potentially enhance their attention skills through an innovative, game-based approach.

Will I have to stop taking my current medications?

The trial does not specify whether you need to stop taking your current medications. However, it does require participants to be on monthly blood transfusions for at least 3 months before starting the trial.

What prior data suggests that this attentional-control training program is safe for children with sickle cell disease?

Research shows that EndeavorRx, a digital therapy game, is safe for children. In studies with 342 kids, researchers found no serious harmful effects, indicating the game didn't cause major problems. Children play the game on a tablet for about 25-30 minutes a day, five days a week, for four weeks. The FDA has approved it to help improve attention in children aged 8-12, providing extra confidence in its safety. So far, evidence suggests that children handle it well for attention training. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about EndeavorRx for sickle cell disease because it offers a unique approach by focusing on attentional control training rather than traditional medical treatments. Unlike standard options that primarily manage pain or complications through medication, EndeavorRx is a video game designed to enhance cognitive function. This innovative digital therapy provides a non-invasive, engaging way for children to improve their attentional skills at home, potentially leading to better quality of life and management of their condition.

What evidence suggests that EndeavorRx is effective for improving attention in children with sickle cell disease?

Research shows that EndeavorRx, a game-based digital therapy, can improve attention and reduce hyperactivity in children. In earlier studies, 73% of children demonstrated better attention after using the program. The therapy adapts to each child's performance, ensuring the challenges remain engaging and appropriate. Initially developed for ADHD, this trial investigates its benefits for children with sickle cell disease who have attention issues. Early results suggest that this adaptable method might help with cognitive problems associated with sickle cell disease. ^{6 7 8 9 10}

Who Is on the Research Team?

Steven J Hardy, Ph.D.

Principal Investigator

Children's National Research Institute

Are You a Good Fit for This Trial?

This trial is for children aged 8-16 with Sickle Cell Disease (SCD) who are on monthly blood transfusions. They must show attention difficulties, evidenced by specific scores on the Conners' CPT-3 or ADHD-RS-V tests.

Inclusion Criteria

diagnosis of SCD

ages 8-16 years

maintained on monthly blood transfusions consistently for at least 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Baseline Testing

Baseline cognitive and attentional assessments conducted before starting the intervention

1 week

1 visit (in-person)

Treatment

Participants engage in EndeavorRx attentional-control training at home for 25-30 minutes each day, 5 days per week, for 4 weeks

4 weeks

Home-based, no in-person visits required

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of cognitive and attentional improvements

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• EndeavorRx

Trial Overview The study tests EndeavorRx, an FDA-approved electronic program designed to improve attention in kids. Participants use it at home for about half an hour daily over four weeks, and its difficulty increases as their performance improves.

How Is the Trial Designed?

Group I: EndeavorRx Experimental Treatment 1 Intervention

Children will be asked to begin attentional control training at home within two weeks of baseline testing and to complete 6 training missions per day (25-30 minutes), 5 days per week, for 4 weeks (total = 120 training missions).

EndeavorRx is already approved in United States for the following indications:

Approved in United States as EndeavorRx for:

• Improving attention function as measured by computer-based testing in children ages 8-12 years old with primarily inattentive or combined-type ADHD, who have a demonstrated attention issue.

Who Is Running the Clinical Trial?

Children's National Research Institute

Lead Sponsor

Trials

227

Recruited

258,000+

Published Research Related to This Trial

Boys with haemophilia (n = 19) exhibited significantly higher levels of hyperactivity-impulsivity (HI) and inattention (IN) as rated by teachers, indicating a potential risk for ADHD-spectrum problems.

The haemophilia group also showed more impulsivity errors on psychometric tasks and had a higher participation rate in special education, suggesting behavioral challenges despite not having significant academic deficits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inattention, hyperactivity-impulsivity, academic skills and psychopathology in boys with and without haemophilia. Spencer, ML., Wodrich, DL., Schultz, W., et al.[2009]

A study of 1,312 children aged 7-10 revealed that reaction time variability (RTV) has a strong genetic link to inattention in ADHD, with a correlation of 0.64, while its link to hyperactivity-impulsivity is much weaker at 0.31.

Commission errors (CE) showed low genetic correlations with both ADHD symptom domains, indicating that different cognitive impairments are genetically distinct and may contribute differently to inattention and hyperactivity-impulsivity in ADHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The separation of ADHD inattention and hyperactivity-impulsivity symptoms: pathways from genetic effects to cognitive impairments and symptoms. Kuntsi, J., Pinto, R., Price, TS., et al.[2021]

A review of 43 studies involving around 7000 children found that common adverse drug reactions (ADRs) from ADHD medications included decreased appetite, gastrointestinal pain, and headaches, primarily reported by children or their parents.

Most studies reported low rates of serious ADRs, but many children dropped out due to serious reactions, suggesting that the actual incidence of serious ADRs may be higher, highlighting the need for long-term safety studies on ADHD medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The occurrence of adverse drug reactions reported for attention deficit hyperactivity disorder (ADHD) medications in the pediatric population: a qualitative review of empirical studies. Aagaard, L., Hansen, EH.[2021]

Game-based digital therapeutics (DTx), like EndeavorRx®, significantly improved inattention and hyperactivity/impulsivity in children with ADHD compared to control groups, based on assessments from parents and teachers.

However, traditional medication was found to be more effective than game-based DTx in reducing inattention and hyperactivity/impulsivity, indicating that while DTx offers a beneficial alternative, it may not replace conventional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of game-based digital therapeutics on attention deficit hyperactivity disorder in children and adolescents as assessed by parents or teachers: a systematic review and meta-analysis. Oh, S., Choi, J., Han, DH., et al.[2023]

In a phase 3 safety study of guanfacine extended release (GXR) involving 215 children and adolescents with ADHD, the treatment was well tolerated, with 82.7% experiencing some treatment-emergent adverse events, primarily somnolence and headache.

GXR significantly reduced ADHD symptoms over the 2-year study, with a mean decrease of 19.8 points in the ADHD-RS-IV total score, indicating its efficacy in managing ADHD symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of guanfacine extended release in children and adolescents with ADHD. Huss, M., Dirks, B., Gu, J., et al.[2018]

Children with ADHD-I and comorbid specific learning disorder (SLD) showed significant improvements in teacher-rated measures after a behavioral intervention (CLAS), but those with ADHD-I only had greater improvements, indicating that SLD may limit the effectiveness of such interventions in school settings.

Despite the challenges, all children, regardless of SLD status, improved on parent-rated measures, suggesting that behavioral interventions can be beneficial for both groups, although some inattention issues may persist specifically in the SLD group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Learning Disorder Confers Setting-Specific Treatment Resistance for Children with ADHD, Predominantly Inattentive Presentation. Friedman, LM., McBurnett, K., Dvorsky, MR., et al.[2021]

In a study of a nonreferred elementary school population, 9.2% of children were observed to have attention-deficit hyperactivity symptoms, with two main subtypes identified: behavioral (80%) and cognitive (20%).

The behavioral subtype is characterized by inattention, impulsivity, and hyperactivity without the specific skill deficits seen in reading disabilities, while the cognitive subtype shows severe academic underachievement and information processing deficits similar to those found in reading disabled children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Behavioral and cognitive subtypes of ADHD. August, GJ., Garfinkel, BD.[2019]

This study will evaluate the effectiveness of a digital game-based attention training program for children with ADHD, involving 104 participants aged 5 to 8 years, over a 5-week period with assessments at multiple time points.

The trial aims to measure improvements in various aspects of attention and executive functioning, using a rigorous double-blind, randomized controlled design to ensure reliable results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Digital cognitive training in children with attention-deficit/hyperactivity disorder: a study protocol of a randomised controlled trial. Richmond, S., Kirk, H., Gaunson, T., et al.[2022]

Child abuse and maternal psychiatric disorders are significant familial risk factors for developing comorbid disruptive behavior disorders (DBD) in children and adolescents with ADHD, based on a study of 144 Japanese subjects aged 5-18.

Risperidone, when added to methylphenidate treatment for ADHD patients resistant to standard therapy, showed a tendency to improve symptoms and was well tolerated, with a response rate of 50% among those treated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictive familial risk factors and pharmacological responses in ADHD with comorbid disruptive behavior disorders. Bandou, N., Koike, K., Matuura, H.[2016]

In a study of 34 young adults with ADHD, the inattentive type was the most common, affecting 50% of participants, while adaptol was found to be effective and safe for treatment, showing improvement in 64.7% of cases over 8 weeks.

The study also highlighted that adult ADHD patients often experience high levels of anxiety and asthenic disorders, indicating the need for comprehensive treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Attention deficit syndrome in adults: clinical, psychophysiological features and treatment]. Chutko, LS., Surushkina, SIu., Iakovenko, EA., et al.[2016]

In a phase IV study involving 255 subjects (143 pediatric and 112 adult), PRC-063 (multilayer-release methylphenidate) significantly reduced ADHD symptoms, with mean ADHD-5-RS score reductions of -16.6 for pediatric and -14.8 for adult subjects (p < 0.001).

PRC-063 was found to be non-inferior to lisdexamfetamine (LDX) in pediatric patients, indicating comparable efficacy, while it was not non-inferior in adults; both medications were well-tolerated, with fewer adverse events leading to discontinuation in the PRC-063 group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Efficacy and Safety of Extended-Release Methylphenidate (PRC-063) in the Treatment of ADHD in Pediatric and Adult Subjects: Results of a Phase IV Multicenter Comparison With Lisdexamfetamine Dimesylate. van Stralen, J., Parhar, G., Parhar, A., et al.[2023]

In a study of 32 children with ADHD, working memory was identified as a significant area of impairment compared to 60 healthy controls, indicating that children with ADHD struggle more with tasks requiring memory retention.

Poor working memory performance in children with ADHD was linked to reported learning problems by parents, suggesting that addressing working memory deficits could help improve academic outcomes for these children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Executive function in children with attention deficit/hyperactivity disorder: the NIH EXAMINER battery. Schreiber, JE., Possin, KL., Girard, JM., et al.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39128918/

Replication across three independent trials of AKL-T01 We aimed to derive a real-time measure of attention from AKL-T01 gameplay data and validate it against clinical outcomes. Trials of AKL-T01 ...

2. endeavorotc.com endeavorotc.com/

EndeavorOTC | A Digital Treatment for Adult ADHD The adult game-based ADHD treatment scientifically designed to improve ADHD-related symptoms and focus. Start your journey to improved focus today.

3. peearz.com peearz.com/trialsindex?nctid=NCT05099874

Feasibility and Efficacy of Attentional-Control Training in ... Children with sickle cell disease (SCD) exhibit significantly reduced cognitive functioning (often difficulties with attention) compared to peers and ...

4. endeavorrx.com endeavorrx.com/the-research/

ADHD Research | EndeavorRx® Study For ADHD in Children 68% of parents reported improvements in ADHD-related impairments after two months of treatment.² ; 73% of children reported an improvement in their attention.¹.

5. withpower.com withpower.com/trial/attentional-control-training-for-sickle-cell-disease-333b9

Attentional-Control Training for Sickle Cell Disease Research shows that EndeavorRx, a game-based digital therapy, has been effective in improving attention and reducing hyperactivity/impulsivity in children with ...

6. endeavorrx.com endeavorrx.com/regulations/

Indications, Safety & Caution | EndeavorRx® No serious adverse events were reported. Of 342 participants who received AKL-T01 in the two clinical trials supporting EndeavorRx authorization for age ranges ...

7. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/reviews/DEN200026.pdf

DEN200026 summary - accessdata.fda.gov EndeavorRx is a digital therapeutic indicated to improve attention function as measured by computer- based testing in children ages 8-12 years old with ...

8. endeavorrx.com endeavorrx.com/

EndeavorRx® - ADHD Video Game Treatment for Kids | FDA ... Safety: No serious adverse events were reported. Of 342 participants who received AKL-T01 in the two clinical trials supporting EndeavorRx authorization for age ...

9. hcpendeavorrx.com hcpendeavorrx.com/

Homepage - EndeavorRx® Safety: No serious adverse events were reported. Of 342 participants who received AKL-T01 in the two clinical trials supporting EndeavorRx authorization for age ...

10. endeavorrx.com endeavorrx.com/wp-content/uploads/2021/08/EndeavorRx_IFU_2_1.pdf

Instructions for Use Safety and Compliance: There were no treatment-related adverse events. 84% of treatment sessions were completed. 1 Davis et al., PLOS One, 2018. 23. TOVA® API ...