Controlled Trial of Lovastatin Combined With an Open-Label Treatment of a Parent-Implemented Language Intervention in Youth With Fragile X Syndrome
Authors: Len Abbeduto, Angela John Thurman, Laura A. Potter, Kyoungmi Kim, Flora Tassone, Amy Banasik, Sarah Nelson Potter, Lauren Bullard, Vivian Nguyen, Andrea McDuffie, and Randi Hagerman from the UC Davis MIND Institute.
Drs. Angela Thurman, Len Abbeduto, Randi Hagerman (UC Davis MIND Institute), and colleagues conducted a clinical trial combining lovastatin with a behavioral intervention called parent-implemented language intervention (PILI). Thanks to NIH funding, these researchers were able to explore whether the combined lovastatin/behavioral therapy approach would be more effective than just behavioral therapy alone.
Lovastatin is an FDA-approved drug used to treat high cholesterol. Lovastatin has been investigated in fragile X, as it may counteract some of the associated challenges related to the FMR1 gene. PILI was delivered through teleconferencing with parents, showing them how to use PILI language-facilitation strategies that incorporate shared storytelling activities and how to ask questions that encourage their child’s participation in a conversation. The study enrolled 30 participants aged 10–17; 16 participants received only PILI and 14 participants received PILI and lovastatin.
The study team suggested the combined lovastatin and behavioral therapy approach may better address learning or behavior problems in individuals with FXS than PILI alone. The study team found significant improvement in both groups, but no additional benefits in the group that received lovastatin. Participants in both groups demonstrated significant changes in the primary outcome measures. They also found that the parents’ progress in learning and using the PILI strategies was associated with their children’s progress in language.
Why This Matters
Understanding language development, a commonly cited challenge for individuals with FXS, is incredibly important. This clinical trial provides additional support for the effectiveness of using PILI in young people with FXS and provides an evidence-based treatment option for older children and adolescents who have fragile X. It also shows the importance of exploring both medical and non-medical treatment options in fragile X, suggesting teleconferencing as an effective modality for delivering treatment.
Researchers would like to understand how to effectively get PILI into the hands of parents. This may take time and more research, but the goal is to be able to share these learnings with parents and caregivers. Validating teleconferencing will help improve access and ability to deliver treatment outside of standard in-person care.
This study was funded by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (U54HD079125) and National Center for Advancing Translational Sciences (NCATS) (UL1 TR000002).
Validation of the NIH Toolbox Cognitive Battery in Intellectual Disability
Authors: Rebecca Shields, Forrest McKenzie, Andrea Drayton, and Stephanie Sansone of UC Davis; Aaron Kaat and Richard Gershon of Northwestern University; Jeanine Coleman and Karen Riley of the University of Denver; Claire Michalak and Elizabeth Berry-Kravis of Rush University Medical Center; and Keith Widaman of the University of California, Riverside.
Researchers at the UC Davis MIND Institute, University of Denver, Northwestern University, Rush University, and University of California, Riverside, have updated and validated a series of tests within the NIH Toolbox (NIHTB) to assess cognition in people with intellectual disability. The validation of NIHTB in individuals with intellectual disabilities opens new opportunities for better, more accurate results in a population that is exceedingly difficult to evaluate.
Led by David Hessl, the study team enrolled 242 individuals with fragile X syndrome (FXS), Down syndrome (DS), and other intellectual and developmental disabilities (ID), ages six through 25 years, and retested after one month. The study team adapted the NIHTB battery by developing accommodations and standard assessment guidelines documented in an e-manual. The researchers determined that all seven tests of the adapted NIHTB could accurately measure cognitive skills in individuals with a mental age of five or above. In individuals with a mental age below five, there was more variability. Some of the tests performed very well, and others need more research and additional modifications before the NIHTB can be equally good at measuring skills in these individuals who are lower functioning.
This test is quick (one hour or less!), feasible for most, and participants were willing and able to respond to the test questions. The test measures a variety of skills, including memory, expressive (what is said) and receptive (what is understood) vocabulary, single-word reading and processing speed, executive functioning (the ability to shift from one thought to another or to pay attention and inhibit impulses), and cognitive flexibility (asking the participant to complete the task one way, then changing the rules so the participant has to complete the task differently). The adapted NIHTB battery found to be reliable; the scores were consistent after retesting individuals.
Why This Matters
It can be challenging to capture an individual’s true ability with a cognitive test. Adapting a cognitive battery to better capture changes in individuals with IDD will help researchers better understand if cognitive changes are occurring in a reliable, objective way. NIHTB has already been used as an outcome measure for clinical trials in fragile X like the metformin trial at UC Davis. Adopting the NIHTB as a standard cognitive battery will help the field move forward, making results easier to compare across studies. Adopting a standard battery will help the field move forward, making results easier to compare across studies. There is also a clinical promise to use the NIHTB.
More research is needed to validate the complete NIHTB in individuals with a mental age of less than five years old. Continued research into the sensitivity of the NIHTB to development/treatment changes is needed.
Funding for the study came from the NICHD (RO1HD076189), the Health and Human Services Administration of Developmental Disabilities (90DD0596), the MIND Institute Intellectual and Developmental Disabilities Research Center (U54 HD079125), and the National Center for Advancing Translational Sciences, National Institutes of Health, through grant UL1 TR000002.
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Last Updated: 10/20/2020