Controlled trial of lovastatin combined with an open-label treatment of a parent-implemented language intervention in youth with fragile X syndrome

Angela John Thurman, Laura A Potter, Kyoungmi Kim, Flora Tassone, Amy Banasik, Sarah Nelson Potter, Lauren Bullard, Vivian Nguyen, Andrea McDuffie, Randi Hagerman, Leonard Abbeduto, Angela John Thurman, Laura A Potter, Kyoungmi Kim, Flora Tassone, Amy Banasik, Sarah Nelson Potter, Lauren Bullard, Vivian Nguyen, Andrea McDuffie, Randi Hagerman, Leonard Abbeduto

Abstract

Background: The purpose of this study was to conduct a 20-week controlled trial of lovastatin (10 to 40 mg/day) in youth with fragile X syndrome (FXS) ages 10 to 17 years, combined with an open-label treatment of a parent-implemented language intervention (PILI), delivered via distance video teleconferencing to both treatment groups, lovastatin and placebo.

Method: A randomized, double-blind trial was conducted at one site in the Sacramento, California, metropolitan area. Fourteen participants were assigned to the lovastatin group; two participants terminated early from the study. Sixteen participants were assigned to the placebo group. Lovastatin or placebo was administered orally in a capsule form, starting at 10 mg and increasing weekly or as tolerated by 10 mg increments, up to a maximum dose of 40 mg daily. A PILI was delivered to both groups for 12 weeks, with 4 activities per week, through video teleconferencing by an American Speech-Language Association-certified Speech-Language Pathologist, in collaboration with a Board-Certified Behavior Analyst. Parents were taught to use a set of language facilitation strategies while interacting with their children during a shared storytelling activity. The main outcome measures included absolute change from baseline to final visit in the means for youth total number of story-related utterances, youth number of different word roots, and parent total number of story-related utterances.

Results: Significant increases in all primary outcome measures were observed in both treatment groups. Significant improvements were also observed in parent reports of the severity of spoken language and social impairments in both treatment groups. In all cases, the amount of change observed did not differ across the two treatment groups. Although gains in parental use of the PILI-targeted intervention strategies were observed in both treatment groups, parental use of the PILI strategies was correlated with youth gains in the placebo group and not in the lovastatin group.

Conclusion: Participants in both groups demonstrated significant changes in the primary outcome measures. The magnitude of change observed across the two groups was comparable, providing additional support for the efficacy of the use of PILI in youth with FXS.

Trial registration: US National Institutes of Health (ClinicalTrials.gov), NCT02642653. Registered 12/30/2015.

Keywords: Distance teleconferencing; Expressive language sampling; Fragile X syndrome; Lovastatin; Narrative storytelling; PILI; Parent-implemented language intervention.

Conflict of interest statement

AJT has received funding for the development and implementation of treatment outcome measures from Fulcrum Therapeutics and the Azrieli Foundation. FT has received funding from the Azrieli Foundation, Zynerba, and Asuragen, Inc., for studies in FXS. RH has received funding from Zynerba, Ovid, and the Azrieli Foundation for treatment studies in children and adults with FXS. She has also consulted with Zynerba and Fulcrum regarding treatment studies in FXS. LA has received funding for the development and implementation of treatment outcome measures from the F. Hoffmann-La Roche Ltd., Roche TCRC, Inc., Neuren Pharmaceuticals Ltd., Fulcrum Therapeutics, Azrieli Foundation, and LuMind IDSC Foundation.

Figures

Fig. 1
Fig. 1
Consolidated standards of reporting trials (CONSORT) flow diagram of subject disposition
Fig. 2
Fig. 2
Means (with standard deviation error bars) for the primary outcome measures as a function of the treatment group. Note that all comparisons are significant (p < .05) after controlling for pre-treatment values

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