Interventions for Reading Disabilities in NF1

NCT02964884 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: 1611591R01HD089474-01
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Neurofibromatosis Type 1; Learning Disability; Reading Disability; NF1

Keywords

Neurofibromatosis Type 1; Learning Disability; Reading Disability; NF1

Outcome Measures

Primary Outcomes (10)

• Woodcock Johnson Tests of Achievement IV

  WJ-IV (Forms A and B) Letter Word Identification, Word Attack, and Passage Comprehension subtests will be administered in order to assess word recognition accuracy, decoding accuracy, and comprehension.

  24 weeks

• Woodcock Reading Mastery Test-III

  (WRMT-III; Forms A and B); Word Identification, Word Attack, and Passage Comprehension will be administered to assess word recognition accuracy, decoding accuracy, and comprehension. The WRMT-III and WJ-III correlate at .87, and at the item level show similar characteristics (e.g., containing 31% and 34% multisyllabic words, respectively).

  24 weeks

• Test of Word Reading Efficiency-2

  (TOWRE-2; Forms A, B, C, D) Sight Word Efficiency and Pseudoword Decoding will be used to assess real and pseudoword reading speed.

  24 weeks

• Experimental Word and Pseudoword Lists

  At each visit, 2 word and 2 pseudoword lists (20 words each) will be administered. Word lists are matched on relevant characteristics (e.g., frequency, bigram frequency). Real word lists have already been developed and tested, and show high inter-correlations (r =.87-.97).

  24 weeks

• Test of Silent Contextual Reading Fluency-2

  (TOSCRF-2; 91; Forms A, B, C, D). This test requires identifying as many words as possible in 3 min within a sentential context.

  24 weeks

• Comprehensive Test of Phonological Processing-2

  CTOPP-2 core subtests will be used to assess phonological processing, a known predictor of decoding and word recognition.

  24 weeks

• Delis Kaplan Executive Function System

  Sorting from the D-KEFS will be used to assess higher-level planning and shifting abilities.

  24 weeks

• Visuospatial Learning and Memory, Morris Water Maze

  The child "hops" from square to square in the grid, repeated from various starting points. After landing on the target square, a fun goal pops up. The number of "hops" to reach the goal is measured. A control probe trial is given in which there is no goal.

  24 weeks

• Visuospatial Learning and Memory, Judgment of Line Orientation

  (JLO, Forms J and H)98 requires the judgment of spatial relationships between two lines compared to a reference of a protractor-like half-circle of 11 lines. The Investigator will create 4 forms from the two already existing by splitting each test in half by selecting every other item, a method used by others (Leach et al., 2003). This will allow us to generate 4 different versions of the JLO.

  24 weeks

• Clinical Evaluation of Language Fundamentals-Fifth Edition

  CELF-5 will be used to assess aspects of oral language (e.g., syntax, semantics, \& working memory).

  24 weeks

Study Arms (4)

NF1: Lovastatin + reading tutoring

ACTIVE COMPARATOR

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

Drug: Lovastatin; Behavioral: reading tutoring intervention

NF1: Placebo + reading tutoring

PLACEBO COMPARATOR

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

Behavioral: reading tutoring intervention; Drug: Placebo Oral Tablet

RD: Reading tutoring

PLACEBO COMPARATOR

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

Behavioral: reading tutoring intervention

RD: Other Academic (sham) tutoring

SHAM COMPARATOR

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.

Behavioral: Other Academic "sham" tutoring

Interventions

Lovastatin DRUG

Those in the Lovastatin group will receive 20mg of Lovastatin per day for the first two weeks and 40mg of Lovastatin per day starting at week 3 through week 11.

NF1: Lovastatin + reading tutoring

reading tutoring intervention BEHAVIORAL

After the initial 12 weeks of Lovastatin or placebo, children will return for one week of intensive, one-on-one tutoring intervention (either reading or sham; Visit 2)

NF1: Lovastatin + reading tutoring; NF1: Placebo + reading tutoring; RD: Reading tutoring

Placebo Oral Tablet DRUG

Those in the placebo group will receive a tablet daily

NF1: Placebo + reading tutoring

Other Academic "sham" tutoring BEHAVIORAL

No reading (sham) tutoring. Children will receive intensive tutoring on a subject other than reading.

RD: Other Academic (sham) tutoring

Eligibility Criteria

• Age: 8 Years - 20 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Individuals ages 8-20 (all participants)
• Documented NF-1 (NF patients only)
• If female, participant is post-menarche (NF patients only)
• If male, participant has reached Tanner Stage 2 (NF patients only)
• Participant able to swallow capsule (NF patients only, may be confirmed via swallowability test, described below)
• Participant's English is sufficient for school (all participants)
• Participant must either answer "yes" to question A, or answer "yes" to at least 2 items for questions B-D listed below:
• A. Has your child ever been diagnosed with a reading disability? B. Did your child have trouble learning how to "sound out" words? C. Have you (parent) ever been concerned about your child's reading ability? D. Did the school or teacher ever express any concerns about your child's reading ability? Swallowability Assessment: We may ask patients to perform a capsule swallowability assessment prior to enrollment. We will ask subjects to attempt to swallow an empty capsule, matching the same size of the Lovastatin 20mg and 40mg capsules to be used in the study, to confirm swallowability. Patients will be provided with up to 2 capsules as needed to successfully perform the swallowability assessment. If the patient is unable to swallow the capsule, enrollment in the study may deferred or declined.
• A child will be excluded if he/she meets any of the following criteria, which will be determined by initial telephone screening as well as review of medical/developmental history prior to and during testing:
• Child 7 years of age or less;
• known uncorrectable visual impairment;
• documented hearing impairment greater than or equal to a 25 dB loss;
• medical contraindication to MRI procedures (e.g., metal devices);
• any psychiatric, behavioral, or developmental disorder that would preclude active participation in in-depth tutoring sessions
• Pregnant at time of screening.

Sponsors & Collaborators

• Vanderbilt University: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

Vanderbilt University

Nashville, Tennessee, United States

Location

MeSH Terms

Conditions

Neurofibromatosis 1; Learning Disabilities; Dyslexia

Interventions

Lovastatin

Condition Hierarchy (Ancestors)

Neurofibromatoses; Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Communication Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurodevelopmental Disorders; Mental Disorders; Language Disorders; Specific Learning Disorder

Intervention Hierarchy (Ancestors)

Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Laurie Cutting, PhD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

• Sheryl L. Rimrodt-Frierson, MD

  Vanderbilt University Medical Center

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 9, 2016
• First Posted: November 16, 2016
• Study Start: November 1, 2016
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: June 24, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)