Cognitive Remediation for Sickle Cell Disease

Overseen By Donna Murdaugh, PhD

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Alabama at Birmingham

Must not be taking: Psychotropic medications

Disqualifiers: Seizures, Stroke, Intellectual disability, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 8

Duration: 4 weeks

120 Participants Needed

Trial Summary

What is the purpose of this trial?

Randomized Controlled Trial (RTC) testing the efficacy of a telehealth adaptation of the Cognitive-Remediation of Executive and Adaptive Deficits in Youth (C-READY) intervention to prepare adolescents with sickle cell disease for transition of care.

Will I have to stop taking my current medications?

If you are currently taking psychotropic medications (drugs that affect your mood, thoughts, or behavior), you will not be able to participate in this trial.

What data supports the effectiveness of the treatment CREADY for cognitive remediation in sickle cell disease?

The pilot study on educational rehabilitation for students with sickle cell disease showed improvements in memory and academic achievement, suggesting that cognitive-focused interventions can be beneficial. Additionally, the review on cognitive endpoints highlights the importance of addressing cognitive and psychological difficulties in sickle cell disease, which CREADY may target. ^{1 2 3 4 5}

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

The CREADY treatment is unique because it focuses on cognitive remediation, aiming to improve cognitive functions like memory and processing speed, which are often affected in sickle cell disease. Unlike traditional treatments that primarily address physical symptoms, CREADY targets the cognitive and psychological challenges associated with the condition. ^{2 3 6 7 8}

Eligibility Criteria

This trial is for English-speaking adolescents aged 10-18 with any type of sickle cell disease (SCD), who are patients at Children's of Alabama Hospital. It excludes those with a history of seizures, stroke, intellectual disabilities or autism, metal implants that prevent MRI scans, severe claustrophobia, or current use of psychotropic medications.

Inclusion Criteria

I have been diagnosed with sickle cell disease.

Active follow-up at Children's of Alabama Hospital

I am between 10 and 18 years old.

Exclusion Criteria

I have had seizures or a stroke.

I am taking medication for my mental health.

You cannot undergo an MRI scan because you have metal implants, neurostimulators, or are claustrophobic.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

C-READY intervention delivered over 4 weeks with 8 telehealth sessions and weekly caregiver phone sessions

4 weeks

8 telehealth sessions, weekly caregiver phone sessions

Follow-up

Participants are monitored for transition readiness skills and cognitive performance post-intervention

4 months

Treatment Details

Interventions

• CREADY

Trial Overview The study tests the CREADY program delivered via telehealth to help teens with SCD transition their healthcare management from pediatric to adult services. This randomized controlled trial assigns participants by chance to either receive this intervention or not.

Participant Groups

Group I: Wait-List Control Group Experimental Treatment 1 Intervention

Will receive the same C-READY intervention after a 4-week wait period

Group II: C-READY (Cognitive-Remediation of Executive and Adaptive Deficits in Youth) Experimental Treatment 1 Intervention

Self-management and goal-setting cognitive remediation

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Findings from Research

In a study of 95 youth with sickle cell disease, a specific measure of self-management skills (SMSC) did not effectively predict successful transition to adult care, indicating a need for better assessment tools.

Caregiver-reported executive functioning, as measured by the BRIEF, showed a weak negative correlation with self-management skills, suggesting that improvements in executive function may not directly enhance transition outcomes for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of transition readiness to predict health care utilization during transition to adult care in sickle cell disease. Howell, KE., Heitzer, AM., Longoria, JN., et al.[2023]

A 2-year educational rehabilitation program for students with sickle cell disease and memory deficits showed promising feasibility, with 82% of the 11 participants completing the program.

Participants demonstrated improvements in both memory and academic achievement, suggesting that educational rehabilitation could be beneficial, warranting further investigation in larger multi-center trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot randomized education rehabilitation trial is feasible in sickle cell and strokes. King, AA., White, DA., McKinstry, RC., et al.[2022]

Cognitive and psychological difficulties, such as issues with executive function and increased anxiety or depression, are significant complications for pediatric patients with sickle cell disease (SCD) and should be considered as important endpoints in clinical trials.

The review identifies specific, reliable cognitive tests and patient-reported outcomes (like the NIH Toolbox Cognition Module and PROMIS scales) that can effectively measure the impact of SCD on patients' daily lives, emphasizing the need for patient-centered approaches in treatment evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Considerations for Selecting Cognitive Endpoints and Psychological Patient-Reported Outcomes for Clinical Trials in Pediatric Patients With Sickle Cell Disease. Hood, AM., Crosby, LE., Stotesbury, H., et al.[2023]

The Kiddie-Sluggish Cognitive Tempo (K-SCT) measure is a reliable and valid tool for assessing sluggish cognitive tempo in children with sickle cell disease (SCD), showing excellent internal consistency and test-retest reliability.

Symptoms of sluggish cognitive tempo are significantly associated with learning difficulties in children with SCD, even when controlling for attention-deficit/hyperactivity disorder (ADHD) symptoms, indicating that SCT may independently impact educational outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sluggish Cognitive Tempo in Pediatric Sickle Cell Disease. Hardy, SJ., Forman, S., Hardy, KK., et al.[2022]

Children and adolescents with sickle cell disease (SCD) showed lower full-scale IQs and performance on the Wechsler Intelligence Scale compared to their healthy siblings, indicating potential cognitive impacts of the disease.

Younger patients with SCD exhibited significantly abnormal scores in areas like expressive speech and memory, suggesting possible subtle neuropsychological deficits that may be linked to subclinical strokes, warranting further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subtle neuropsychological deficits in children with sickle cell disease. Wasserman, AL., Wilimas, JA., Fairclough, DL., et al.[2019]

Children with sickle cell disease (SCD) showed significant cognitive weaknesses in areas such as general cognitive ability, short-term memory, and processing speed, based on a study of 50 children with SCD compared to 36 peers without the disease.

Anemia severity was a strong predictor of cognitive performance, and its effects varied depending on the child's socioeconomic status, suggesting that interventions may need to consider both medical and social factors to effectively support cognitive development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interactions of biomedical and environmental risk factors for cognitive development: a preliminary study of sickle cell disease. Schatz, J., Finke, R., Roberts, CW.[2019]

In a study of 2436 individuals with sickle cell disease, self-reported cognitive difficulties, particularly in executive functioning and comprehension, were linked to poorer performance in daily living activities and lower medication adherence.

Cognitive dysfunction is common among adolescents and adults with sickle cell disease, and monitoring these cognitive symptoms can help healthcare providers better understand and address the functional challenges faced by these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported neurocognitive symptoms influence instrumental activities of daily living in sickle cell disease. Longoria, JN., Pugh, NL., Gordeuk, V., et al.[2022]

The Sickle Cell Disease Program for Learning and Neuropsychological Evaluation (SCD-PLANE) significantly improved access to neuropsychological testing for youth with sickle cell disease, identifying previously unmet cognitive and behavioral needs.

Results showed that despite normal intelligence, patients exhibited increased risks for issues with executive function, processing speed, and emotional symptoms, highlighting the importance of integrated neuropsychological support in routine care for this high-risk population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transition planning for youth with sickle cell disease: embedding neuropsychological assessment into comprehensive care. Wills, KE., Nelson, SC., Hennessy, J., et al.[2010]

References

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

Assessment of transition readiness to predict health care utilization during transition to adult care in sickle cell disease. [2023]

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

A pilot randomized education rehabilitation trial is feasible in sickle cell and strokes. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Considerations for Selecting Cognitive Endpoints and Psychological Patient-Reported Outcomes for Clinical Trials in Pediatric Patients With Sickle Cell Disease. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Sluggish Cognitive Tempo in Pediatric Sickle Cell Disease. [2022]

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

Subtle neuropsychological deficits in children with sickle cell disease. [2019]

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

Interactions of biomedical and environmental risk factors for cognitive development: a preliminary study of sickle cell disease. [2019]

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

Patient-reported neurocognitive symptoms influence instrumental activities of daily living in sickle cell disease. [2022]

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

Transition planning for youth with sickle cell disease: embedding neuropsychological assessment into comprehensive care. [2010]