Intervention Effectiveness on the Neurocognitive Functioning of Children and Adolescents With Neurofibromatosis Type 1
Condition: Neurocognitive Deficit; Mental Health Impairment; Neurofibromatosis 1
MeSH terms: Neurofibromatoses; Neurofibromatosis 1; Neurofibroma
Study type: Interventional

Summary: 
      Children with neurofibromatosis are more likely to have difficulties related to their
      psychological and neurocognitive functioning (e.g., more likely to have depression, have
      social difficulties, be diagnosed with ADHD). The purpose of this randomized control study is
      to determine how effective and useful this study's single session intervention can be in
      improving psychological and neurocognitive functioning. Enrolled families will consist of one
      parent/guardian and child. Parents and patients will complete questionnaires and objective
      tests at baseline, 3 months, and 6 months. Families randomized to the intervention arm will
      be provided with one single session intervention at Month 1 to learn about their child's
      testing results and receive psychoeducation and recommendations related to psychological and
      neurocognitive functioning.
    

Detailed description: 
      Neurofibromatosis type 1 (NF1) is a chronic illness that is typically diagnosed during
      childhood and is associated with a variety of medical, psychological, and neurocognitive
      symptoms. NF1 is a genetic disorder, affecting about 1 in 3,000 people throughout the world.
      Diagnosis usually occurs in childhood and is characterized by the presence of several
      markers, including, but not limited to: multiple café au lait (light brown) skin spots,
      neurofibromas (small benign growths) on or under the skin, optic pathway gliomas, bone
      dysplasia, and freckling in the armpits or groin. Aside from its medical manifestations, NF1
      also is associated with psychological impairment and a wide variety of neurocognitive
      deficits. In comparison to healthy peers and the general population, children and adolescents
      with NF1 have been found to have more social difficulties (e.g., more peer conflicts, fewer
      friends), internalizing symptoms (e.g., anxiety, depression, withdrawal), externalizing
      symptoms (e.g., sub-threshold or clinical symptoms consistent with ADHD such as inattention,
      hyperactivity, impulsivity), sleep difficulties; and worse quality of life. Additionally,
      while the vast majority of children with NF1 have intelligence in the average to low average
      range, neurocognitive deficits have been found in a range of domains including: linguistic
      development, verbal concept formation, reasoning, visuospatial skills, motor skills,
      executive function (e.g., cognitive flexibility, working memory, inhibitory control),
      academic achievement (e.g., reading/spelling, math), and attention. There is further support
      that early onset of mental health problems are associated with both future mental health
      problems and poorer functional outcomes in adulthood (e.g., unemployment, lower earnings,
      lower academic attainment).

      Children with NF are more likely to be diagnosed with Attention-Deficit/Hyperactivity
      Disorder (ADHD) than their healthy counterparts. Early detection, prevention, and
      intervention of psychological and neurocognitive risk may serve as a protective factor for
      later adverse outcomes. A meta-analysis of 175 research studies worldwide on ADHD in children
      ages 18 and younger found an overall pooled estimate of 7.2% of children and adolescents
      diagnosed with ADHD within the general population; however, ADHD is over-represented within
      the NF1 population, with an estimated 31 to 50% of children meeting diagnostic criteria for
      ADHD. Although there is limited research investigating the longitudinal impact of ADHD and NF
      on pediatric patients, longitudinal studies of children with ADHD document deficits in
      multiple domains including lower levels of education, poorer social functioning, and worse
      occupational outcomes. Therefore, children with comorbid diagnoses of both NF1 and ADHD or
      even those NF patients with sub-threshold symptoms of ADHD are likely to be at an increased
      risk for functional deficits later in life.

      Given the general current demand for psychological services, there is a great need for brief,
      problem-focused psychological interventions targeting psychological and neurocognitive
      functioning in NF. Emerging data indicate a significant increase in mental health needs as a
      result of the COVID-19 pandemic, which is consistent with previous large-scale disasters and
      pandemics. This is a significant healthcare crisis given that prior to the pandemic in the
      United States, more than 11.8 million people reported having unmet mental health needs. This
      translates to more individuals needing mental health intervention without access; and,
      subsequently challenges mental health providers to expand services through novel models of
      intervention delivery (e.g., delivering brief problem-focused interventions based on findings
      from standardized assessments in unconventional settings, such as, during multidisciplinary
      medical visits for their medical condition). One novel delivery method of psychological
      services is the single-session intervention (SSI), which is defined as the intentional
      delivery of one visit or encounter with a clinic, provider, or program. Although there is no
      current research investigating the feasibility and clinical effectiveness of SSI's for
      pediatric patients diagnosed with NF, a meta-analysis of 50 randomized control trials of
      SSI's for youth with psychological problems showed a significant beneficial effect (g=0.32),
      with greatest effect sizes for reducing anxiety (g=0.56) and conduct problems (g=0.54).
      Although psychoeducation-based SSI's often were found to have a small effect size, a
      systematic review of 13 studies conducted between 1990 and 2018 that investigated the effects
      of psychoeducation-based interventions on youth with ADHD showed moderate to large effects on
      ADHD symptom improvement as reported by parents/teachers (g=0.787), and parent/teacher and
      child knowledge about ADHD (g=1.037 and g=0.721, respectively).

      This is a pilot feasibility study comprising a randomized controlled trial involving
      patients' ages 6 to 16 years (n=50) with NF. Patients will complete standardized assessment
      batteries and questionnaires assessing their neurocognitive, executive, and psychological
      functioning. The present study will yield longitudinal patterns of neurocognitive and
      psychosocial outcomes across the six month period, and, collect data for preliminary
      development of a single session intervention. In order to gather information on how patients
      perform and behave in different settings, patients, parents, and teachers will also complete
      standardized questionnaires to gather information on psychological functioning over a six
      month period. Given NF is associated with psychological impairment and a wide variety of
      neurocognitive deficits, as well as poorer functional outcomes in adulthood, there is a great
      need for early detection, prevention, and intervention for this vulnerable patient
      population.

      The proposed study has the following specific aims: Aim 1) Examine the preliminary
      feasibility and acceptability of using a single-session intervention focused on
      psychoeducation and cognitive behavioral-based recommendations related to psychological,
      neurocognitive, and executive functioning over six months. Hypothesis 1a: We hypothesize that
      families will report high acceptability for the intervention. Hypothesis 1b: It is
      hypothesized that families assigned to the intervention group will demonstrate improvements
      in both objective and subjective assessments of psychological and neurocognitive symptoms,
      e.g., inattention and impulsivity, as well as, executive functioning when compared to those
      in the control group. Aim 2) Examine descriptive and longitudinal patterns of psychological
      and neurocognitive factors (e.g., intellectual functioning, executive functioning, attention)
      across six months for the sample overall, as well as, for those in the intervention and
      control groups. Hypothesis 2a: It is hypothesized that a similar prevalence of ADHD for
      patients with NF that is seen in the literature (i.e., between 31-50%) will also be observed
      in our sample. Hypothesis 2b: It is hypothesized that there will be individual differences in
      neurocognitive patterns (e.g., executive functioning, attention) across six months in
      pediatric patients with neurofibromatosis (NF) with significant intra-sample variability,
      including differences observed between those who participated in the intervention versus
      those who did not. We suspect that there will be subgroups of patients who have increases in
      attention difficulties and executive function deficits over time, another subgroup will have
      decreases in attention difficulties and executive function deficits over time, and a subgroup
      who will have stable patterns across six months.

      STUDY DESIGN

      Approach:

      Overview of Study Design: The current design is a pilot feasibility study comprising a
      randomized controlled trial involving patients ages 6 to 16 years (n=50) who are diagnosed
      with NF and followed by the comprehensive multidisciplinary NF clinic (Dr. Wang, Director;
      Dr. Rohan, Co-Director). The proposed study will contribute to new knowledge by describing
      trajectories of neurocognitive factors over time; as well as, examining the preliminary
      feasibility and effectiveness of a single-session intervention on improving psychological and
      neurocognitive factors such as attention and executive functioning.

      This comprehensive measurement approach provides a powerful tool to address important
      scientific and clinically relevant questions: 1) What are the patterns of neurocognitive
      symptom presentation in pediatric NF?; and, how do these symptoms relate to psychosocial and
      health outcomes over time?; 2) How might patients and families benefit from receiving
      psychoeducation about neurocognitive, executive, and psychological functioning in patients
      with NF; as well as receiving tailored recommendations based on results of neurocognitive
      assessments? The use of multiple measures of neurocognitive functioning (multiple reporters
      and objective and subjective assessment methods), standardized questionnaires, and a
      single-session intervention in a pilot feasibility study of patients' ages 6 to 16 years is
      an innovative approach that has potential clinical utility and impact. For example,
      identification of neurocognitive and executive functioning deficits from multiple informants
      may allow development of more precise interventions in different settings for children (e.g.,
      school, home). This approach also affords the opportunity to identify risk and protective
      factors in living with a chronic illness and to develop preventative and therapeutic
      interventions that can be delivered at the point of care to minimize barriers and maximize
      facilitators associated across the illness trajectory for this vulnerable patient population.

      Study Procedures Recruitment and Data Collection: Eligible families seen in the Pediatric NF
      Clinic at VCU will be invited to participate via telephone or in person (depending on timing
      of clinic visit). Interested patients and parents/caregivers will provide informed consent,
      parental permission, and assent prior to data collection. Consented participants will be
      randomly allocated to the intervention (n=25) or control (n=25) groups via a computerized
      randomization program.

      Data collection will occur at four timepoints: baseline (T0), 3-months (T1), 6-months (T2),
      and 7-months (T3). At T0 through T2, patients will complete standardized assessment batteries
      for neurocognitive functioning; and, patients, parents, and teachers will complete
      standardized questionnaires. All measures used within the present study are well validated
      and can be administered longitudinally within these time intervals with acceptable
      test-retest reliability. At T3, families in the intervention group will complete
      semi-structured qualitative interviews about the feasibility, acceptability, and desirability
      of the intervention.
    

Intervention name(s): OPTIMAL-SSI
Intervention type(s): Behavioral
Intervention description(s): The purpose of the intervention feedback session will be twofold: 1) to provide the results of the previous assessment, and 2) to provide general psychoeducation on psychological and neurocognitive functioning and tailored cognitive and behavioral interventions based on the results in order to reduce the impact of psychological and neurocognitive deficits.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This is a pilot feasibility study comprising a randomized controlled trial involving 50 families (i.e., parent/guardian AND child ages 6 to 16 years with NF). Consented participants will be randomly allocated to the intervention (n=25) or control (n=25) arms.
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Health Services Research
Keywords: Neurofibromatosis; Neurocognitive; Intervention