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.
Neurofibromitosis Type 1 (NF1) is a common autosomal dominant neurocutaneous syndrome. The most common concern of NF1 is learning disabilities (LDs). Approximately half of children with NF1 have LDs, the most common of which are reading disabilities (RDs).The purpose of this research is to gain a deeper understanding of the characteristics and treatment of RDs in NF1. The Investigator will evaluate four different groups (see list below) to determine if there are differential outcomes in these groups of children with NF+RD. The first two groups will consist of NF1 patients, and the second two groups will consist of participants with RDs but without NF1. 1. Reading tutoring program and a medication called Lovastatin (NF1 patients) 2. Reading tutoring program and no Lovastatin (placebo) (NF1 patients) 3. Reading tutoring program (RD participants) 4. Other Academic "Sham" tutoring (eligible to receive reading tutoring after study participation is complete) (RD participants)
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
120
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.
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)
Those in the placebo group will receive a tablet daily
No reading (sham) tutoring. Children will receive intensive tutoring on a subject other than reading.
Vanderbilt University
Nashville, Tennessee, United States
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.
Time frame: 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).
Time frame: 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.
Time frame: 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).
Time frame: 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.
Time frame: 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.
Time frame: 24 weeks
Delis Kaplan Executive Function System
Sorting from the D-KEFS will be used to assess higher-level planning and shifting abilities.
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: 24 weeks
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