Combining Lovastatin and a Parent-Implemented Language Intervention for Fragile X Syndrome
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|ClinicalTrials.gov Identifier: NCT02642653|
Recruitment Status : Completed
First Posted : December 30, 2015
Last Update Posted : November 16, 2018
|Condition or disease||Intervention/treatment||Phase|
|Fragile X Syndrome Genetic Diseases||Drug: Lovastatin Other: Placebo||Phase 4|
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 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||30 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Combining Lovastatin and a Parent-Implemented Language Intervention in a Multimodal Treatment for Fragile X Syndrome|
|Actual Study Start Date :||January 2016|
|Actual Primary Completion Date :||July 2018|
|Actual Study Completion Date :||July 2018|
Active Comparator: Lovastatin and PILI
Subjects will receive the Parent Implemented Language Intervention (PILI) in combination with study medication Lovastatin.
Once per day dosing
Other Name: Mevacor
Placebo Comparator: Placebo and PILI
Subjects will receive the Parent Implemented Language Intervention (PILI) in combination with placebo.
Once per day dosing
- Change from baseline in the participant and parent/caregiver Expressive Language Sample composite score in the home [ Time Frame: Baseline, 20 weeks ]The expressive language sample is collected from shared interactions around a digital wordless picture book involving the participant with fragile X syndrome and the parent/caregiver in the family home. The composite is created from separate measures of the number of different words used by the participant and the mean length of the communication units measured in morphemes. Samples are collected pre- and post-treatment using different digital books on each occasion, with improvement in the composite expected from pre to post.
- Change from baseline in the participant and mother Expressive Language Sample composite score in the clinic [ Time Frame: Baseline, 20 weeks ]The expressive language sample is collected from shared interactions around a wordless picture book involving the participant with fragile X syndrome and the parent/caregiver in the clinic. The composite is created from separate measures of the number of different words used by the participant and the mean length of the communication units measured in morphemes. Samples are collected pre- and post-treatment using different books on each occasion, with improvement in the composite expected from pre to post.
- Change from baseline in the FXS- normed Aberrant Behavior Checklist (ABC) social avoidance subscale [ Time Frame: Baseline, 10 weeks, 20 weeks ]The ABC-C is a 58- item caregiver-rated behavior scale used to examine treatment effects on challenging behaviors for individuals with FXS in the following domains: (1) irritability, agitation, crying; (2) lethargy, social withdrawal; (3) stereotypic behavior (4) hyperactivity, noncompliance; and (5) inappropriate speech. The social avoidance subscale will be analyzed utilizing the Sansone et al. (2011) FXS-normed ABC scoring measures.
- Change from baseline of Symptoms in Fragile X using the Clinical Global Impression-Improvement (CGI-I) scale [ Time Frame: Baseline, 10 weeks, 20 weeks ]A clinician rated scale utilizing history from the parents or caregiver and incorporating it into a clinical rating, first for severity, and then for clinical follow-up. The CGI-S will be used at the pre-treatment assessment to judge symptom severity and the CGI- I will be used at the 10 week and 20 week visits.
- Change from baseline in the Visual Analog Scale (VAS) [ Time Frame: Baseline, 10 weeks, 20 weeks ]The measure will be used to assess parental impressions of progress in two key symptoms: spoken language impairment and social impairment. The distance of the mark from one end is used as the outcome variable for analysis.
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): NCT02642653
|United States, California|
|UC Davis MIND Institute|
|Sacramento, California, United States, 95817|
|Principal Investigator:||Randi J Hagerman, MD||UC Davis|