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Trial record 28 of 62 for:    Dyslexia

Interventions for Reading Disabilities in NF1

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ClinicalTrials.gov Identifier: NCT02964884
Recruitment Status : Recruiting
First Posted : November 16, 2016
Last Update Posted : February 22, 2019
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Laura Cutting, Vanderbilt University

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.

Condition or disease Intervention/treatment Phase
Neurofibromatosis Type 1 Learning Disability Reading Disability NF1 Drug: Lovastatin Behavioral: reading tutoring intervention Drug: Placebo Oral Tablet Behavioral: Other Academic "sham" tutoring Phase 2

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)

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Neurobiology and Treatment of Reading Disability in NF1
Actual Study Start Date : November 2016
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : June 2022


Arm Intervention/treatment
Active Comparator: 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

Drug: Lovastatin
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.

Behavioral: reading tutoring intervention
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)

Placebo Comparator: NF1: Placebo + reading tutoring
Participants (NF-1 patients) will receive placebo daily And one week of intensive, one-on-one reading tutoring intervention
Behavioral: reading tutoring intervention
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)

Drug: Placebo Oral Tablet
Those in the placebo group will receive a tablet daily

Placebo Comparator: RD: Reading tutoring
Participants (RD-only participants) will receive one week of intensive, one-on-one reading tutoring intervention
Behavioral: reading tutoring intervention
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)

Sham Comparator: 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.

Behavioral: Other Academic "sham" tutoring
No reading (sham) tutoring. Children will receive intensive tutoring on a subject other than reading.




Primary Outcome Measures :
  1. 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.

  2. 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).

  3. 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.

  4. 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).

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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).



Information from the National Library of Medicine

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Ages Eligible for Study:   8 Years to 20 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02964884


Contacts
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Contact: Julie Delheimer, BS 615-875-5534 educationbrain@vanderbilt.edu
Contact: Lanier P. Sachs, M.E.d 615-936-1167 virginia.l.prichard@vanderbilt.edu

Locations
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United States, Tennessee
Vanderbilt University Recruiting
Nashville, Tennessee, United States
Contact: Laura E. Cutting    615-875-1054      
Sponsors and Collaborators
Vanderbilt University
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
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Principal Investigator: Laurie Cutting, PhD Vanderbilt University Medical Center
Study Director: Sheryl L. Rimrodt-Frierson, MD Vanderbilt University Medical Center

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Responsible Party: Laura Cutting, Principal Investigator, Vanderbilt University
ClinicalTrials.gov Identifier: NCT02964884     History of Changes
Other Study ID Numbers: 161159
1R01HD089474-01 ( U.S. NIH Grant/Contract )
First Posted: November 16, 2016    Key Record Dates
Last Update Posted: February 22, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Laura Cutting, Vanderbilt University:
Neurofibromatosis Type 1
Learning Disability
Reading Disability
NF1

Additional relevant MeSH terms:
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Dyslexia
Neurofibromatoses
Neurofibromatosis 1
Neurofibroma
Learning Disorders
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
Genetic Diseases, Inborn
Peripheral Nervous System Diseases
Neuromuscular Diseases
Peripheral Nervous System Neoplasms
Nervous System Neoplasms
Communication Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Signs and Symptoms
Neurodevelopmental Disorders
Mental Disorders
Language Disorders
Lovastatin
L 647318
Dihydromevinolin
Anticholesteremic Agents