Neurobiology and Treatment of Reading Disability in NF1
Overview
- Phase
- Phase 2
- Intervention
- Lovastatin
- Conditions
- Neurofibromatosis Type 1
- Sponsor
- Vanderbilt University
- Enrollment
- 120
- Locations
- 1
- Primary Endpoint
- Woodcock Reading Mastery Test-III
- Status
- Active, Not Recruiting
- Last Updated
- 10 months ago
Overview
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.
Detailed Description
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)
Investigators
Laura Cutting
Principal Investigator
Vanderbilt University
Eligibility Criteria
Inclusion Criteria
- •This study will be open to all English speakers who meet eligibility criteria regardless of race, gender, minority or socioeconomic status. Inclusion criteria to be met are listed below:
- •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:
Exclusion Criteria
- Not provided
Arms & Interventions
NF1: Lovastatin + reading tutoring
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
Intervention: Lovastatin
NF1: Lovastatin + reading tutoring
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
Intervention: reading tutoring intervention
NF1: Placebo + reading tutoring
Participants (NF-1 patients) will receive placebo daily And one week of intensive, one-on-one reading tutoring intervention
Intervention: reading tutoring intervention
NF1: Placebo + reading tutoring
Participants (NF-1 patients) will receive placebo daily And one week of intensive, one-on-one reading tutoring intervention
Intervention: Placebo Oral Tablet
RD: Reading tutoring
Participants (RD-only participants) will receive one week of intensive, one-on-one reading tutoring intervention
Intervention: reading tutoring intervention
RD: Other Academic (sham) tutoring
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.
Intervention: Other Academic "sham" tutoring
Outcomes
Primary Outcomes
Woodcock Reading Mastery Test-III
Time Frame: 24 weeks
(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).
Test of Silent Contextual Reading Fluency-2
Time Frame: 24 weeks
(TOSCRF-2; 91; Forms A, B, C, D). This test requires identifying as many words as possible in 3 min within a sentential context.
Comprehensive Test of Phonological Processing-2
Time Frame: 24 weeks
CTOPP-2 core subtests will be used to assess phonological processing, a known predictor of decoding and word recognition.
Woodcock Johnson Tests of Achievement IV
Time Frame: 24 weeks
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.
Test of Word Reading Efficiency-2
Time Frame: 24 weeks
(TOWRE-2; Forms A, B, C, D) Sight Word Efficiency and Pseudoword Decoding will be used to assess real and pseudoword reading speed.
Delis Kaplan Executive Function System
Time Frame: 24 weeks
Sorting from the D-KEFS will be used to assess higher-level planning and shifting abilities.
Experimental Word and Pseudoword Lists
Time Frame: 24 weeks
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).
Visuospatial Learning and Memory, Morris Water Maze
Time Frame: 24 weeks
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.
Visuospatial Learning and Memory, Judgment of Line Orientation
Time Frame: 24 weeks
(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.
Clinical Evaluation of Language Fundamentals-Fifth Edition
Time Frame: 24 weeks
CELF-5 will be used to assess aspects of oral language (e.g., syntax, semantics, \& working memory).