Interventions for Reading Disabilities in NF1

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Brief Title

Interventions for Reading Disabilities in NF1

Official Title

Neurobiology and Treatment of Reading Disability in NF1

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)

Study Phase

Phase 2

Study Type

Interventional

Primary Outcome

Woodcock Johnson Tests of Achievement IV

Condition

Neurofibromatosis Type 1

Intervention

Lovastatin

Study Arms / Comparison Groups

 NF1: Lovastatin + reading tutoring

Description:  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

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status

Drug

Estimated Enrollment

Start Date

November 2016

Completion Date

July 2022

Primary Completion Date

May 2022

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:

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.

Gender

All

Ages

8 Years - 20 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Laurie Cutting, PhD, 615-875-5534, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations

NCT ID

NCT02964884

Organization ID

Secondary IDs

1R01HD089474-01

Responsible Party

Principal Investigator

Study Sponsor

Vanderbilt University

Collaborators

 Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Study Sponsor

Laurie Cutting, PhD, Principal Investigator, Vanderbilt University Medical Center

Verification Date

January 2021