Combining Lovastatin and a Parent-Implemented Language Intervention for Fragile X Syndrome
Condition: Fragile X Syndrome; Genetic Diseases
MeSH terms: Fragile X Syndrome; Genetic Diseases, Inborn; Syndrome
Study type: Interventional
Phase: Phase 4

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.
    

Detailed description: 
      This is the first multi-modal treatment to combine a targeted treatment for FXS, lovastatin,
      with an innovative parent-implemented intervention (PILI) targeting language and challenging
      behavior delivered through telehealth technology.The hypothesis is that targeted treatments
      will be more effective when applied in combination with PILI. Examination of whether changes
      in the activity of key pathways/proteins influenced by fragile X mental retardation protein
      (FMRP) (the mitogen-activated protein kinase (ERK) and MMP-9) are biomarkers of treatment
      responsiveness. Because lovastatin is also an anti-inflammatory, characterization of MEK/ERK
      signaling in peripheral immune cells both pre- and post- treatment will be carried out to
      determine whether levels of these signaling molecules are predictive biomarkers of treatment
      response. It is hypothesized that those individuals with elevated inflammatory cytokine
      profiles will be most responsive to lovastatin treatment. Once modeled in FXS, results from
      these studies can then be applied to other neurodevelopmental disorders including
      RASopathies.

      The behavioral component of the proposed multi-modal treatment will be a Parent-implemented
      Intervention (PILI) that targets improvements in spoken language and challenging behavior for
      10- to 17-year-olds with FXS by increasing parental verbal responsiveness (PVR) within
      picture-book based story-telling episodes. Parents will be encouraged to use the targeted
      strategies in other everyday interactions with their child. The intervention will be
      delivered to parents in their homes by way of video teleconferencing (VTC). Participants will
      be randomly assigned to receive the behavioral intervention alone or in combination with
      Lovastatin.
    

Intervention name(s): Lovastatin; Placebo
Intervention type(s): Drug; Other
Intervention description(s): Once per day dosing; Once per day dosing
Other intervention name(s): Mevacor
Intervention MeSH terms: Lovastatin; L 647318; Dihydromevinolin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
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