Medication + Reading Tutoring for Learning Disabilities in Neurofibromatosis Type 1

Overseen By Lanier P. Sachs, M.E.d

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Vanderbilt University

Must be taking: Lovastatin

Must not be taking: Psychotropic medications

Disqualifiers: Epilepsy, Metabolic Syndrome, Liver Problems, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 13 weeks

120 Participants Needed

Trial Summary

What is the purpose of this trial?

Neurofibromatosis Type 1 (NF1) is a common genetic disorder that is associated with a four times greater risk of learning disabilities, including reading disabilities, and a deficiency of neurofibromin - a protein important in a signaling pathway that regulates learning and memory. Our previous work (NS49096) demonstrated that school-age children with NF+RD can respond to standard phonologically-based reading tutoring originally developed to treat reading disability in the general population. Combining our work with that by other researchers suggesting that a medication (Lovastatin) may counteract the effects of the deficient neurofibromin, and possibly ameliorate learning disabilities in NF1, the investigator propose to examine the synergistic effects of medication plus reading tutoring.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that participants should not be on psychotropic medications, except for stimulant medication for ADHD. If you are taking other medications, it's best to discuss this with the trial coordinators.

What data supports the effectiveness of the treatment for learning disabilities in children with neurofibromatosis type 1?

Research shows that phonics training, a type of reading tutoring, can improve reading skills in children with neurofibromatosis type 1 who have reading difficulties. Additionally, attention, which affects reading comprehension, is a key area to address in these children, suggesting that targeted reading interventions could be beneficial. ^{1 2 3 4 5}

How is the Reading Tutoring Intervention treatment different from other treatments for learning disabilities in Neurofibromatosis Type 1?

The Reading Tutoring Intervention is unique because it focuses on phonics training, which helps children with Neurofibromatosis Type 1 improve their reading skills by teaching them how to connect sounds with letters. This approach is particularly beneficial for children with NF1 who often struggle with phonological dyslexia, a condition where they have difficulty using spelling-to-sound rules to read. ^{1 2 5 6 7}

Research Team

Laurie Cutting, PhD

Principal Investigator

Vanderbilt University Medical Center

Sheryl L. Rimrodt-Frierson, MD

Principal Investigator

Vanderbilt University Medical Center

Eligibility Criteria

This trial is for English-speaking individuals aged 8-20 with Neurofibromatosis Type 1 (NF1) and reading disabilities. They must be able to swallow capsules, have documented NF-1, and females should be post-menarche. Exclusions include living outside the US, pregnancy, liver or severe kidney issues, recent surgery or injury, excessive alcohol use, certain medications or conditions contraindicating Lovastatin.

Inclusion Criteria

I speak English and am open to participating regardless of my background.

I am a female and have started menstruating.

I have a confirmed diagnosis of Neurofibromatosis type 1.

Exclusion Criteria

I had a stroke due to brain bleeding and have memory loss.

You have a mental, behavioral, or developmental condition that would make it difficult for you to take part in detailed tutoring sessions.

My child cannot take Lovastatin due to their condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Lovastatin or placebo and one week of intensive, one-on-one reading tutoring intervention

13 weeks

Weekly visits for medication monitoring and tutoring sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

11 weeks

Bi-weekly visits (in-person)

Open-label extension (optional)

Participants may opt into continuation of reading tutoring long-term

Long-term

Treatment Details

Interventions

• Lovastatin
• Reading Tutoring Intervention

Trial Overview The study tests if a medication called Lovastatin combined with specialized reading tutoring can help improve learning disabilities in those with NF1. Participants will either receive Lovastatin or a placebo tablet alongside real or 'sham' academic tutoring to compare effects on their reading abilities.

Participant Groups

Group I: NF1: Lovastatin + reading tutoring Active Control 2 Interventions

Participants (NF-1 patients) will receive 20mg of Lovastatin per day for the first two weeks, the dose will be escalated 40 mg for the remaining 11 weeks. And one week of intensive, one-on-one reading tutoring intervention

Group II: RD: Other Academic (sham) tutoring Placebo Group 1 Intervention

Participants (RD-only participants) will receive one week of intensive, one-on-one tutoring intervention with an academic focus other than reading. These participants will have the opportunity to receive reading tutoring upon finishing study participation.

Group III: NF1: Placebo + reading tutoring Placebo Group 2 Interventions

Participants (NF-1 patients) will receive placebo daily And one week of intensive, one-on-one reading tutoring intervention

Group IV: RD: Reading tutoring Placebo Group 1 Intervention

Participants (RD-only participants) will receive one week of intensive, one-on-one reading tutoring intervention

Reading Tutoring Intervention is already approved in United States for the following indications:

Approved in United States as Reading Tutoring Intervention for:

• Reading Disabilities in Neurofibromatosis Type 1 (NF1)

Who Is Running the Clinical Trial?

Vanderbilt University

Lead Sponsor

Trials

714

Recruited

6,143,000+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Findings from Research

A 24-week phonics-training program significantly improved various literacy skills in 30 children aged 7-12 with neurofibromatosis type 1 (NF1), with improvements in reading accuracy, letter-sound knowledge, and phonemic decoding fluency, among others.

The effectiveness of the intervention was influenced by age and working memory, with older children and those with better verbal working memory showing the greatest improvements, and these gains were maintained 8 weeks after the treatment ended.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phonics Training Improves Reading in Children with Neurofibromatosis Type 1: A Prospective Intervention Trial. Arnold, SS., Barton, B., McArthur, G., et al.[2019]

Children and adolescents with Neurofibromatosis type 1 (NF1) and reading deficits showed significant improvement in reading skills when participating in intensive remedial teaching, while untreated groups did not show any progress.

Among the different multisensory reading programs, those with greater kinesthetic demands were more effective for the NF1 group, suggesting that tailored interventions focusing on movement may better support their learning needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teaching reading to children with neurofibromatosis type 1: a clinical trial with random assignment to different approaches. Barquero, LA., Sefcik, AM., Cutting, LE., et al.[2022]

Cognitive and behavioral disorders are prevalent in nearly 80% of children with neurofibromatosis type 1 (NF1), significantly impacting their quality of life and that of their families.

Research using small-animal models has identified promising therapeutic targets for addressing learning, attention, and autism spectrum disorders in children with NF1, highlighting the need for further studies to develop effective treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive and behavioral problems in children with neurofibromatosis type 1: challenges and future directions. Schwetye, KE., Gutmann, DH.[2022]

A study of 81 children with neurofibromatosis type 1 (NF1) revealed that 81% experienced moderate to severe cognitive impairments, particularly in areas like reading, spelling, and mathematics, with 63% facing sustained attention difficulties.

Despite these challenges, children with NF1 showed relatively stronger verbal and visual memory skills compared to their overall intellectual functioning, indicating that while cognitive deficits are prevalent, certain memory abilities remain intact.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The nature and frequency of cognitive deficits in children with neurofibromatosis type 1. Hyman, SL., Shores, A., North, KN.[2022]

In a study of 150 children aged 8-12, attention significantly influenced reading comprehension in both children with neurofibromatosis type 1 (NF1) and those without, highlighting the importance of attentional skills in reading performance.

The study found that performance-based measures of attention correlated better with reading comprehension than parent-reported questionnaires, suggesting that both types of assessments are necessary for a comprehensive understanding of attention difficulties in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reading Comprehension Impairment in Children With Neurofibromatosis Type 1 (NF1): The Need of Multimodal Assessment of Attention. Biotteau, M., Tournay, E., Baudou, E., et al.[2022]

Children with neurofibromatosis type 1 (NF1) show significantly poorer literacy skills compared to typically developing peers, with 49 out of 60 classified as poor readers, primarily suffering from phonological and mixed dyslexia.

Key predictors of better reading skills in children with NF1 include stronger working memory, better receptive language abilities, and fewer inattentive behaviors, highlighting the importance of these cognitive skills in addressing reading difficulties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Profiling the Word Reading Abilities of School-Age Children with Neurofibromatosis Type 1. Arnold, SS., Payne, JM., McArthur, G., et al.[2021]

In a study of 30 children with Neurofibromatosis type 1 (NF1), 67% showed deficits in reading skills, with 75% of those meeting criteria for phonological dyslexia, indicating a significant prevalence of reading impairments in this population.

The findings suggest that many children with NF1 struggle specifically with sublexical reading skills, which involve using spelling-to-sound rules, and highlight that traditional methods for identifying reading difficulties may not be effective for this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An examination of lexical and sublexical reading skills in children with neurofibromatosis type 1. Watt, SE., Shores, A., North, KN.[2022]

References

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

Phonics Training Improves Reading in Children with Neurofibromatosis Type 1: A Prospective Intervention Trial. [2019]

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

Teaching reading to children with neurofibromatosis type 1: a clinical trial with random assignment to different approaches. [2022]

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

Cognitive and behavioral problems in children with neurofibromatosis type 1: challenges and future directions. [2022]

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

The nature and frequency of cognitive deficits in children with neurofibromatosis type 1. [2022]

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

Reading Comprehension Impairment in Children With Neurofibromatosis Type 1 (NF1): The Need of Multimodal Assessment of Attention. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Profiling the Word Reading Abilities of School-Age Children with Neurofibromatosis Type 1. [2021]

7. England pubmed.ncbi.nlm.nih.gov

An examination of lexical and sublexical reading skills in children with neurofibromatosis type 1. [2022]