Attentional-Control Training for Sickle Cell Disease

(ACT Trial)

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

Trial Summary

What is the purpose of this trial?

Children with sickle cell disease (SCD) exhibit significantly reduced cognitive functioning (often difficulties with attention) compared to peers and siblings without SCD. EndeavorRx (Akili Interactive Labs: Boston, MA) is an FDA-approved home-based, electronic attentional-control training program designed to treat attention problems in youth. Users access EndeavorRx on a tablet device for 25-30 minutes each day, 5 days per week, for 4 weeks. The program involves training in a game-like environment that repeatedly challenges attentional-control abilities and adapts to user performance, becoming more difficult over time as performance improves. This pilot study is examining the feasibility, acceptability, and preliminary efficacy of EndeavorRx in a sample of 20 children with SCD ages 8-16 who are being treated with chronic blood transfusion therapy.

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 data supports the effectiveness of the treatment EndeavorRx 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 ADHD, as reported by parents and teachers. This suggests that similar digital therapies might help manage attention-related issues in other conditions, like Sickle Cell Disease. ^{1 2 3 4 5}

Is Attentional-Control Training for Sickle Cell Disease safe for humans?

There is no specific safety data available for Attentional-Control Training under the names EndeavorRx, AKL-T01, or Project: EVO ADHD Treatment in the provided research articles. ^{6 7 8 9 10}

How is the treatment EndeavorRx different from other treatments for sickle cell disease?

EndeavorRx is unique because it is a digital treatment designed to improve attention and cognitive function, originally developed for children with ADHD. Unlike traditional medications for sickle cell disease, which often focus on managing pain or preventing complications, EndeavorRx uses a video game format to target attention and cognitive skills, offering a novel approach to addressing cognitive challenges associated with the condition. ^{1 3 4 11 12}

Research Team

Steven J Hardy, Ph.D.

Principal Investigator

Children's National Research Institute

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Inattention, hyperactivity-impulsivity, academic skills and psychopathology in boys with and without haemophilia. [2009]

2. England pubmed.ncbi.nlm.nih.gov

Learning Disorder Confers Setting-Specific Treatment Resistance for Children with ADHD, Predominantly Inattentive Presentation. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Digital cognitive training in children with attention-deficit/hyperactivity disorder: a study protocol of a randomised controlled trial. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Behavioral and cognitive subtypes of ADHD. [2019]

5. Germany 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. [2023]

6. New Zealand 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. [2021]

7. Germany pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of guanfacine extended release in children and adolescents with ADHD. [2018]

8. Australia pubmed.ncbi.nlm.nih.gov

Predictive familial risk factors and pharmacological responses in ADHD with comorbid disruptive behavior disorders. [2016]

9. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Attention deficit syndrome in adults: clinical, psychophysiological features and treatment]. [2016]

10. United States 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. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Executive function in children with attention deficit/hyperactivity disorder: the NIH EXAMINER battery. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

The separation of ADHD inattention and hyperactivity-impulsivity symptoms: pathways from genetic effects to cognitive impairments and symptoms. [2021]