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

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.

SUBMITTER: Thurman AJ

PROVIDER: S-EPMC7175541 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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

Thurman Angela John AJ Potter Laura A LA Kim Kyoungmi K Tassone Flora F Banasik Amy A Potter Sarah Nelson SN Bullard Lauren L Nguyen Vivian V McDuffie Andrea A Hagerman Randi R Abbeduto Leonard L

Journal of neurodevelopmental disorders 20200422 1

<h4>Background</h4>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.<h4>Method</h4>A randomized, double-blind trial was conducted at one site in the Sacramento, California, metropolitan area. Fourteen p ...[more]

PMID: 32316911

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Project description:Purpose Early intervention using augmentative and alternative communication (AAC) supports both receptive and expressive language skills. However, many parents and clinicians still worry that augmented language intervention might delay or impair speech development. This study aimed to (a) characterize and analyze the speech sound development of toddlers with developmental delay who participated in a parent-implemented language intervention; (b) examine the accuracy of speech sounds among toddlers who participated in an augmented language intervention using speech-generating devices and toddlers who participated in a traditional, spoken language intervention; and (c) examine the relationship between baseline factors (i.e., receptive and expressive language skills, vocal imitation, and number of unintelligible utterances) and the number of spoken target vocabulary words after intervention. Method This study used extant data from two randomized control trials of parent-implemented language interventions using AAC or spoken language. Out of 109 children who completed the intervention, 45 children produced spoken target vocabulary words at the end of the intervention. We identified and phonetically transcribed spoken target vocabulary words for each child and then classified them based on Shriberg and Kwiatkowski's (1982) developmental sound classes. Results Children's speech sound accuracy was not significantly different across intervention groups. Overall, children who produced more words had more speech sound errors and higher baseline language scores. Intervention group and baseline receptive and expressive language skills significantly predicted the number of spoken target vocabulary words produced at the end of intervention. Conclusions Participation in AAC intervention resulted in significantly more spoken target vocabulary words and no statistically significant differences in speech sound errors when compared to children who received spoken language intervention without AAC. Results support using AAC interventions for very young children without the fear that it will delay speech or spoken language development. Supplemental Material https://doi.org/10.23641/asha.14265365.

Project description:Several qualitative and quantitative features of parental speech input support children's language development and may play a critical role in improving such process in late talkers. Parent-implemented interventions targeting late-talkers have been developed to promote children's language outcomes by enhancing their linguistic environment, i.e., parental speech input. This study investigated the effect of a parent-implemented intervention in increasing late talkers' expressive skills through modifications in structural and functional features of parental speech input. Forty-six thirty-one-month-old late talkers differing in their birth condition (either low-risk preterm or full-term) participated in the study with a parent; 24 parent-child dyads received a parent-implemented intervention centered on dialogic reading and focused stimulation techniques, whereas the other 22 dyads constituted the control group. At pre- and post-intervention, dyads took part in a parent-child shared book-reading session and both parental and child's speech measures were collected and examined. Results showed that the intervention positively affected parents' use of responses and expansions of children's verbal initiatives, as well as the parental amount of talking over reading, whereas no structural features of parental input resulted modified. Mediation analyses pointed out that the intervention indirectly enhanced late-talkers' use of verbal types and tokens through changes in parental use of expansions and amount of talking over reading. As birth status was entered as a covariate in the analysis, these findings can be extended to children with different gestational age. We conclude that the parent-implemented intervention was effective in supporting late-talkers' gains in language development as a cascade result of the improvements in parental contingency and dialogic reading abilities. These promising findings suggest to examine not only children and parental outcomes but also the intervention mechanisms promoting changes in late-talkers' language development as a clearer view on such process can inform the development of feasible, ecological and effective programs.

Project description:Fragile X syndrome (FXS) is a disorder characterized by a variety of disabilities, including cognitive deficits, attention-deficit/hyperactivity disorder, autism, and other socio-emotional problems. It is hypothesized that the absence of the fragile X mental retardation protein (FMRP) leads to higher levels of matrix metallo-proteinase-9 activity (MMP-9) in the brain. Minocycline inhibits MMP-9 activity, and alleviates behavioural and synapse abnormalities in fmr1 knockout mice, an established model for FXS. This open-label add-on pilot trial was conducted to evaluate safety and efficacy of minocycline in treating behavioural abnormalities that occur in humans with FXS.Twenty individuals with FXS, ages 13-32, were randomly assigned to receive 100 mg or 200 mg of minocycline daily. Behavioural evaluations were made prior to treatment (baseline) and again 8 weeks after daily minocycline treatment. The primary outcome measure was the Aberrant Behaviour Checklist-Community Edition (ABC-C) Irritability Subscale, and the secondary outcome measures were the other ABC-C subscales, clinical global improvement scale (CGI), and the visual analog scale for behaviour (VAS). Side effects were assessed using an adverse events checklist, a complete blood count (CBC), hepatic and renal function tests, and antinuclear antibody screen (ANA), done at baseline and at 8 weeks.The ABC-C Irritability Subscale scores showed significant improvement (p < 0.001), as did the VAS (p = 0.003) and the CGI (p < 0.001). The only significant treatment-related side effects were minor diarrhea (n = 3) and seroconversion to a positive ANA (n = 2).Results from this study demonstrate that minocycline provides significant functional benefits to FXS patients and that it is well-tolerated. These findings are consistent with the fmr1 knockout mouse model results, suggesting that minocycline modifies underlying neural defects that account for behavioural abnormalities. A placebo-controlled trial of minocycline in FXS is warranted.ClinicalTrials.gov Open-Label Trial NCT00858689.

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Dataset Information

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

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

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