Clinical trial NCT02964884: Interventions for Reading Disabilities in NF1
Official title: Neurobiology and Treatment of Reading Disability in NF1
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Neurofibromatosis Type 1
Learning Disability
Reading Disability
NF1
Keywords: Neurofibromatosis Type 1
Learning Disability
Reading Disability
NF1
Lead sponsor: Vanderbilt University
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2016-11-16
Enrollment: 120
Sex: ALL
Minimum age (years): 8
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)

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:

1. Individuals ages 8-20 (all participants)
2. Documented NF-1 (NF patients only)
3. If female, participant is post-menarche (NF patients only)
4. If male, participant has reached Tanner Stage 2 (NF patients only)
5. Participant able to swallow capsule (NF patients only, may be confirmed via swallowability test, described below)
6. Participant's English is sufficient for school (all participants)
7. 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:

1. Child 7 years of age or less;
2. known uncorrectable visual impairment;
3. documented hearing impairment greater than or equal to a 25 dB loss;
4. medical contraindication to MRI procedures (e.g., metal devices);
5. any psychiatric, behavioral, or developmental disorder that would preclude active participation in in-depth tutoring sessions
6. Pregnant at time of screening.
7. Known conditions which are contraindicated to Lovastatin

   1. Hypersensitivity to the medication
   2. Uncontrolled Epilepsy
   3. Metabolic Syndrome X, High Blood Sugar,
   4. Muscle Damage Due to Autoimmunity
   5. Stroke caused by Bleeding in the Brain, Loss of Memory,
   6. Severely Low Blood Pressure
   7. Liver Problems including Abnormal Liver Function Tests
   8. Severe Renal Impairment,
   9. Serious Muscle Damage that may Lead to Kidney Failure,
   10. Recent Operation or significant Injury
   11. Muscle Pain or Tenderness with Increase Creatinine Kinase,
   12. Habit of Drinking Too Much Alcohol
   13. Pregnant or lactating. - Lovastatin is contraindicated during pregnancy and in nursing mothers because it decreases synthesis of cholesterol and other products of the cholesterol biosynthesis pathway that are essential components for fetal development.

Children who meet criteria for ADHD, Oppositional Defiant Disorder, adjustment disorder, and/or mild depression will be eligible as long as they are not taking psychotropic medications, with the exception of stimulant medication for ADHD.

For pilot participants only:

Criteria for inclusion/exclusion for pilot participants is outlined below. Children who meet criteria for ADHD, Oppositional Defiant Disorder, adjustment disorder, and/or mild depression will be eligible as long as they are not taking psychotropic medications, with the exception of stimulant medication for ADHD.

1. Children ages 8-17
2. Participant is a native English speaker
3. Participant must either answer "yes" to question A, or answer "yes" to at least 2 items for questions 2-4 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?

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:

1. Children 7 years of age or younger
2. previous diagnosis of Intellectual Disability;
3. known uncorrectable visual impairment;
4. documented hearing impairment greater than or equal to a 25 dB loss;
5. medical contraindication to MRI procedures (e.g., metal devices);
6. known IQ below 70;
7. a pervasive developmental disorder; and
8. any known neurologic pathology, including epilepsy, spina bifida, cerebral palsy, traumatic brain injury, optic gliomas, and brain tumors (other than UBOs).
9. Comorbid severe psychiatric disorders will also be excluded.

Primary outcomes:
measure: Woodcock Johnson Tests of Achievement IV
timeFrame: 24 weeks
measure: Woodcock Reading Mastery Test-III
timeFrame: 24 weeks
measure: Test of Word Reading Efficiency-2
timeFrame: 24 weeks
measure: Experimental Word and Pseudoword Lists
timeFrame: 24 weeks
measure: Test of Silent Contextual Reading Fluency-2
timeFrame: 24 weeks
measure: Comprehensive Test of Phonological Processing-2
timeFrame: 24 weeks
measure: Delis Kaplan Executive Function System
timeFrame: 24 weeks
measure: Visuospatial Learning and Memory, Morris Water Maze
timeFrame: 24 weeks
measure: Visuospatial Learning and Memory, Judgment of Line Orientation
timeFrame: 24 weeks
measure: Clinical Evaluation of Language Fundamentals-Fifth Edition
timeFrame: 24 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
Study officials:
affiliation: Vanderbilt University Medical Center
name: Laurie Cutting, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Vanderbilt University Medical Center
name: Sheryl L. Rimrodt-Frierson, MD
role: STUDY_DIRECTOR
References: