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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining Lovastatin, a medication, with reading tutoring can help children with Neurofibromatosis Type 1 (NF1) improve their learning and reading skills. NF1 is a genetic condition that can lead to learning challenges. By testing medication alongside tutoring, researchers aim to find a better way to support these children's educational progress. Children struggling with reading and who have NF1 or a diagnosed reading disability might be a good fit for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that Lovastatin is generally safe for people and is often used to lower cholesterol. Studies have found that most people tolerate it well. For those with Neurofibromatosis Type 1 (NF1), Lovastatin has been tested for its potential to help with learning problems. However, it did not improve certain learning skills, such as understanding visual information or paying attention, in children with NF1.

Regarding reading tutoring, past research indicates it can help children with NF1 who struggle with reading. This tutoring focuses on the sounds of words to improve reading skills and has already been shown to help kids with reading difficulties in the general population.

Researchers are studying these treatments together to determine if they work better when combined. Overall, existing studies support the safety of Lovastatin and the effectiveness of reading tutoring, suggesting they are safe options to explore further. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer a unique approach to managing learning disabilities in individuals with Neurofibromatosis Type 1 (NF1). Unlike traditional methods, which often focus solely on educational interventions, this trial combines reading tutoring with Lovastatin, a medication usually used to lower cholesterol. Lovastatin is being explored for its potential neurological benefits, which could enhance learning and cognitive function in NF1 patients. By targeting both the educational and biochemical aspects of learning disabilities, this approach could provide a more comprehensive treatment strategy.

What evidence suggests that this trial's treatments could be effective for learning disabilities in Neurofibromatosis Type 1?

This trial will evaluate two treatments for learning disabilities in children with Neurofibromatosis Type 1 (NF1). Participants in one arm will receive Lovastatin, a medication that has shown effectiveness in improving learning problems in animal studies of NF1, suggesting potential benefits for people with the condition. Another arm will involve reading tutoring, proven effective for children with both NF1 and reading difficulties. Past studies have shown that phonics-based reading programs significantly improve reading skills in these children. Together, these treatments could potentially offer a combined approach to addressing learning disabilities associated with NF1. ^{3 5 6 7 8}

Who Is on the Research Team?

Sheryl L. Rimrodt-Frierson, MD

Principal Investigator

Vanderbilt University Medical Center

Laurie Cutting, PhD

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

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 am a female and have started menstruating.

I have a confirmed diagnosis of Neurofibromatosis type 1.

Participants may be asked to perform a swallowability assessment prior to enrollment

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4818747/

A randomized placebo‐controlled lovastatin trial for ...

Lovastatin has been shown to reverse learning deficits in a mouse model of Neurofibromatosis Type 1 (NF1), a common monogenic disorder caused by a mutation ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02964884

NCT02964884 | Interventions for Reading Disabilities in NF1

Neurofibromatosis Type 1 (NF1) is a common genetic disorder that is associated with a four times greater risk of learning disabilities, including reading ...

3.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0887899411003146

Lovastatin as Treatment for Neurocognitive Deficits in ...

In a neurofibromatosis type 1 murine model, treatment with lovastatin reversed cognitive disabilities. We report on a phase I study examining the safety and ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4015838/

Lovastatin improves impaired synaptic plasticity and phasic ...

The HMG-CoA reductase inhibitor lovastatin reverses the learning and attention deficits in a mouse model of neurofibromatosis type 1. Curr Biol. 2005;13(21): ...

5.

sciencedirect.com

sciencedirect.com/science/article/pii/S0960982205011139

The HMG-CoA Reductase Inhibitor Lovastatin Reverses ...

We report that lovastatin decreased the enhanced brain p21Ras-MAPK activity of the nf1 +/− mice, rescued their LTP deficits, and reversed their spatial ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5207004/

Randomized placebo-controlled study of lovastatin in ...

This study provides Class I evidence that for children with NF1, lovastatin does not improve visuospatial learning or attention deficits. With a birth incidence ...

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT00352599?term=AREA%5BBasicSearch%5D(neurofibromatosis)&rank=8

Trial to Evaluate the Safety of Lovastatin in Individuals With ...

Data collected at the beginning of a clinical study for all participants and for each arm or comparison group. These data include demographics, such as age, sex ...

8.

clinicaltrials.gov

clinicaltrials.gov/study/NCT00352599

NCT00352599 | Trial to Evaluate the Safety of Lovastatin in ...

Lovastatin is a medication commonly used to treat high cholesterol and has been proven to be relatively safe and tolerable in humans. The investigators are now ...