Combining Lovastatin and a Parent-Implemented Language Intervention for Fragile X Syndrome

NCT02642653 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: 520144
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to test the efficacy of a 20 week multi-modal treatment comprised of lovastatin or placebo, and the Parent-implemented Language Intervention (PILI) in children with fragile X syndrome (FXS). Children will be randomized to drug or placebo in a double-blind design with all participating in the PILI. The primary endpoint will be to measure improvements in spoken language and behavior among lovastatin-treated than placebo treated participants.

Conditions

Fragile X Syndrome; Genetic Diseases

Keywords

Fra(X) Syndrome; Trinucleotide Repeat Expansion; Fragile X Syndrome; Fragile X Mental Retardation Syndrome; Intellectual Disability; Parent Implemented Language Intervention (PILI); FXS; Mental Retardation, X-linked; Genetic Diseases, X-linked; Neurobehavioral Manifestations; Chromosome Disorders

Outcome Measures

Primary Outcomes (2)

• Expressive Language Sample Composite Score in the Home

  The primary outcome reflects the diversity of vocabulary used. Higher scores reflect more skill. The lowest possible value is zero. No theoretical maximum can be defined because the wordless picture books can lead to a large and indeterminate set of options for the amount of talk and the vocabulary used. In a previous study of a nonpharmacological intervention, the range at baseline was 9-177, and at post-treatment, the range for the combined treated and nontreated groups was 23-214, although these values were not corrected for the number of C-units produced (McDuffie at el. 2018 Developmental Neurorehabilitation).

  Baseline

• Expressive Language Sample Composite Score in the Home

  The primary outcome reflects the diversity of vocabulary used. Higher scores reflect more skill. The lowest possible value is zero. No theoretical maximum can be defined because the wordless picture books can lead to a large and indeterminate set of options for the amount of talk and the vocabulary used. In a previous study of a nonpharmacological intervention, the range at baseline was 9-177, and at post-treatment, the range for the combined treated and nontreated groups was 23-214, although these values were not corrected for the number of C-units produced (McDuffie at el. 2018 Developmental Neurorehabilitation).

  20 weeks

Secondary Outcomes (12)

• FXS- Normed Aberrant Behavior Checklist (ABC) Social Avoidance Subscale

  Baseline

• FXS- Normed Aberrant Behavior Checklist (ABC) Social Avoidance Subscale

  10 weeks

• FXS- Normed Aberrant Behavior Checklist (ABC) Social Avoidance Subscale

  20 weeks

• Clinical Global Impression- Severity (CGI-S)

  Baseline

• Clinical Global Impression-Improvement (CGI-I) Scale

  10 weeks

Study Arms (2)

Lovastatin and PILI

ACTIVE COMPARATOR

Subjects will receive the Parent Implemented Language Intervention (PILI) in combination with study medication Lovastatin.

Drug: Lovastatin

Placebo and PILI

PLACEBO COMPARATOR

Subjects will receive the Parent Implemented Language Intervention (PILI) in combination with placebo.

Other: Placebo

Interventions

Lovastatin DRUG

Once per day dosing

Also known as: Mevacor

Lovastatin and PILI

Placebo OTHER

Once per day dosing

Placebo and PILI

Eligibility Criteria

• Age: 10 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Documentation of a full mutation with absence or deficient FMRP levels.
• Males and females ages 10 through 17 years
• Willingness of potential study participant as well as a parent or caretaker to participate in the protocol.
• Speech is the primary means of communication with three-word or longer utterances used on a daily basis.
• Intelligence quotient (IQ) ≤70 as measured by the Leiter- R.
• Sexually active women of childbearing potential (WCBP) must be using a medically acceptable method of birth control and have a negative qualitative serum β-human chorionic growth hormone (β-HCG) or urine pregnancy test collected at the initial screening visit.

You may not qualify if:

• Persons who do not speak English.
• Changes in any medications (including investigational medications) within the last month (4 weeks). All concomitant medications must have been on a stable course for at least 4 weeks prior to enrollment into the study and maintain stability throughout the course of the study.
• Changes in behavioral therapy or educational programming during the study. This does not include scheduled school holidays.
• Have any disease or condition (medical or surgical) at screening that might compromise the hematologic, cardiovascular, pulmonary, renal, gastrointestinal, or hepatic systems; or other conditions that might interfere with the absorption, distribution, metabolism, or excretion of the investigational product, or would place the subject at increased risk.
• Patients who, in the opinion of the investigator, are unsuitable in any other way to participate in this study, including being unable to comply with the requirements of the study or displaying clinically significant abnormalities in safety assessments at screening.
• Patients on prohibited medications
• History of recurrent status epilepticus.
• Inability to withhold grapefruit and grapefruit juice from diet during the entire clinical trial.
• Subjects unwilling to abstain from alcoholic beverages during the trial.
• Subjects who are actively suicidal.

Sponsors & Collaborators

• University of California, Davis: lead

Study Sites (1)

UC Davis MIND Institute

Sacramento, California, 95817, United States

Location

Related Publications (1)

• Thurman AJ, Potter LA, Kim K, Tassone F, Banasik A, Potter SN, Bullard L, Nguyen V, McDuffie A, Hagerman R, Abbeduto L. Controlled trial of lovastatin combined with an open-label treatment of a parent-implemented language intervention in youth with fragile X syndrome. J Neurodev Disord. 2020 Apr 22;12(1):12. doi: 10.1186/s11689-020-09315-4.

  PMID: 32316911 DERIVED

MeSH Terms

Conditions

Fragile X Syndrome; Genetic Diseases, Inborn; Intellectual Disability; X-Linked Intellectual Disability; Genetic Diseases, X-Linked; Neurobehavioral Manifestations; Chromosome Disorders

Interventions

Lovastatin

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Nervous System Diseases; Sex Chromosome Disorders; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Limitations and Caveats

The study did not have a cohort treated only with lovastatin without the parent-implemented language intervention (PILI). The efficacy of the study medication alone compared to placebo can't be evaluated.

Results Point of Contact

• Title: Dr. Randi Hagerman
• Organization: University of California Davis

rjhagerman@ucdavis.edu

9167030247

Study Officials

• Randi J Hagerman, MD

  UC Davis

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2015
• First Posted: December 30, 2015
• Study Start: January 1, 2016
• Primary Completion: July 1, 2018
• Study Completion: July 1, 2018
• Last Updated: September 11, 2019
• Results First Posted: September 11, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)