Neurobiology and Treatment of Reading Disability in NF-1

Neurobiology and Treatment of Reading Disability in Neurofibromatosis Type 1 (NF-1)

The goal of this trial is to determine if children with neurofibromatosis type 1 who have reading disabilities respond the same way-both behaviorally and neurobiologically-to specialized treatment programs as children with idiopathic reading disabilities do, and to determine which intervention is best for particular learner profiles.

Study Overview

• Status: Completed
• Conditions: Neurofibromatosis Type 1; Reading Disabilities
• Intervention / Treatment: Behavioral: Tutoring Program I; Behavioral: Tutoring Program II

Detailed Description

The most common concern of parents of children with neurofibromatosis type 1 (NF-1) is learning disabilities (LD). Approximately one half of all children with NF-1 have LD-the most debilitating and common of which are reading disabilities.

The purpose of this study is to determine if children with NF-1 who have reading disabilities respond the same way-both behaviorally and neurobiologically-to specialized treatment programs known to improve the decoding deficits in children with idiopathic reading disabilities. The trial will also determine which intervention is best for particular learner profiles. The overall purpose of this research is to gain a deeper understanding of the characteristics and treatment of reading disabilities in NF-1.

In the trial, researchers will compare children with NF-1 who show weaknesses in reading to children with reading disabilities of no known cause (idiopathic) using two different interventions and behavioral and neurobiological measures. Both interventions focus on teaching sound-symbol relationships, but vary in terms of relative emphasis on verbal versus visual methods of teaching.

Scientists hope findings from the trial will advance knowledge about the best therapies for LD in children with NF-1. And, by further refining how children with NF-1 who have reading disabilities are similar (or different) to children with idiopathic reading disabilities, the researchers may be able to learn if reading interventions that address areas other than decoding will also benefit children with NF-1. Also, by understanding the similarities and/or differences in the neuropsychological and neurobiological profiles of children with NF-1 who have reading disabilities, and those without, scientists will be able to refine the cognitive phenotype and neurobiological characteristics of NF-1, which will further understanding of central nervous system abnormalities in NF-1.

• Study Type: Interventional
• Enrollment (Actual): 184
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232-2310
      • Vanderbilt University, Vanderbilt University Institute of Imaging Science

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 17 years (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

This study will be open to all individuals, ages 8 to 17 years, who meet eligibility criteria regardless of race, gender, or socioeconomic status.

• The Reading Disabilities group (including those with NF-1) is defined by scoring equal to or less than the 25th percentile on measures of basic word reading skills.
• The Control group (including those with NF1) is defined by scoring equal to or above the 40th percentile on the average of the Letter Word Identification and Word Attack subtests from the WJ-III.

Exclusion Criteria:

Any child, regardless of which group he/she is recruited for, will be excluded if he/she meets any of the following criteria (determined during phone screening, medical review, and during testing):

• is in foster care;
• previous diagnosis of mental retardation;
• known uncorrectable visual impairment;
• history of known neurological disorder (e.g., epilepsy, spina bifida, cerebral palsy, traumatic brain injury);
• documented hearing impairment greater than 25 dB loss in either ear;
• medical contraindication to MRI procedures, if participating in MRI (including exposure to metal and pregnancy);
• individuals known to have an IQ below 70;
• history or presence of a pervasive developmental disorder;
• during the DICA-IV parents indicate the presence of any severe psychiatric diagnoses or pervasive developmental disorder.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NF-Tutoring Program 1; Tutoring Program I	Behavioral: Tutoring Program I; Tutoring Program I is a structured multi-sensory program that is designed to gradually present the range of sounds and letters with focus on accuracy of phonological concepts and application of those concepts in phrases and sentences. The instruction uses a sequenced defined lesson plan with accuracy and automaticity criteria for skill progression. A range of manipulative and kinesthetic activities is outlined to maintain learner engagement in the intensive intervention design.
Experimental: NF-Tutoring Program 2; Tutoring Program II	Behavioral: Tutoring Program II; Tutoring Program II is designed to teach visual and speech elements of reading separately at first, and then bring them together for maximum efficiency. The program uses the idea of teaching concepts about the structure of words. For example, students transfer the rules they have learned about one vowel or structure to another without specific instructions on the new one. Tutoring Program II incorporates pictures and activities to help remember strategies for increasing basic reading skills. Speed drills are also used for development of decoding automaticity.
No Intervention: Typically Developing Readers; Control group
Experimental: IRD-Tutoring Program 1; Tutoring Program I	Behavioral: Tutoring Program I; Tutoring Program I is a structured multi-sensory program that is designed to gradually present the range of sounds and letters with focus on accuracy of phonological concepts and application of those concepts in phrases and sentences. The instruction uses a sequenced defined lesson plan with accuracy and automaticity criteria for skill progression. A range of manipulative and kinesthetic activities is outlined to maintain learner engagement in the intensive intervention design.
Experimental: IRD-Tutoring Program 2; Tutoring Program II	Behavioral: Tutoring Program II; Tutoring Program II is designed to teach visual and speech elements of reading separately at first, and then bring them together for maximum efficiency. The program uses the idea of teaching concepts about the structure of words. For example, students transfer the rules they have learned about one vowel or structure to another without specific instructions on the new one. Tutoring Program II incorporates pictures and activities to help remember strategies for increasing basic reading skills. Speed drills are also used for development of decoding automaticity.
No Intervention: Waitlist Control; Intervention Control Group (RD)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in WJ-III Basic Reading Normative Update (Woodcock Johnson Psychoeducational Battery - 3rd Edition; WJ-III NU) Standard Score at 15 Hours	This metric measures change in reading abilities, including word recognition and decoding, as assessed by standard educational assessments (Woodcock Johnson Psychoeducational Battery - 3rd Edition Normative Update; WJ-III NU). The scores are reported as change in age-normed standard scores (a change of 15 standard score points would represent a change of 1 standard deviation in the general population).The Basic Reading score is a normed composite of the WJ-III subtests Letter-Word Identification and Word Attack, representing word-level reading skill.	0 and 15 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neuroimaging Data	Neuroimaging data consists of functional MRI and structural MRI measures.	Collected before and after intervention

Collaborators and Investigators

• Sponsor: Vanderbilt University
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: Laurie E. Cutting, Ph.D., Vanderbilt University Special Education Department; Principal Investigator: Martha Bridge Denckla, M.D., Kennedy Krieger Institute, Johns Hopkins University, Johns Hopkins University School of Medicine; Principal Investigator: Sheryl L. Rimrodt, M.D., Vanderbilt University Pediatrics Department; Principal Investigator: John Gore, Ph.D., Vanderbilt University

Publications and helpful links

Helpful Links

• Additional study information

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2006
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: February 25, 2008
• First Submitted That Met QC Criteria: February 25, 2008
• First Posted (Estimated): February 27, 2008

Study Record Updates

• Last Update Posted (Actual): July 8, 2025
• Last Update Submitted That Met QC Criteria: June 18, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: neurofibromatosis type 1; NF-1; reading disabilities; learning disabilities; tutoring intervention
• Additional Relevant MeSH Terms: Specific Learning Disorder; Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Neoplasms; Neuromuscular Diseases; Genetic Diseases, Inborn; Peripheral Nervous System Diseases; Neoplasms by Histologic Type; Neurobehavioral Manifestations; Neurodegenerative Diseases; Neurodevelopmental Disorders; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Heredodegenerative Disorders, Nervous System; Nerve Sheath Neoplasms; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Peripheral Nervous System Neoplasms; Communication Disorders; Language Disorders; Learning Disabilities; Neurofibromatoses; Neurofibromatosis 1; Neurofibroma; Dyslexia
• Other Study ID Numbers: R01NS049096 (U.S. NIH Grant/Contract); NF1-R01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified behavioral data (Woodcock Johnson-III NU scores) may be shared with other researchers upon request. De-identified T1 structural neuroimaging scans will be shared with other researchers through a neuroimaging data warehouse or consortium.