Fasoracetam in adolescents with ADHD and glutamatergic gene network variants disrupting mGluR neurotransmitter signaling.
Publication/Presentation Date
1-16-2018
Abstract
The glutamatergic neurotransmitter system may play an important role in attention-deficit hyperactivity disorder (ADHD). This 5-week, open-label, single-blind, placebo-controlled study reports the safety, pharmacokinetics and responsiveness of the metabotropic glutamate receptor (mGluR) activator fasoracetam (NFC-1), in 30 adolescents, age 12-17 years with ADHD, harboring mutations in mGluR network genes. Mutation status was double-blinded. A single-dose pharmacokinetic profiling from 50-800 mg was followed by a single-blind placebo at week 1 and subsequent symptom-driven dose advancement up to 400 mg BID for 4 weeks. NFC-1 treatment resulted in significant improvement. Mean Clinical Global Impressions-Improvement (CGI-I) and Severity (CGI-S) scores were, respectively, 3.79 at baseline vs. 2.33 at week 5 (P < 0.001) and 4.83 at baseline vs. 3.86 at week 5 (P < 0.001). Parental Vanderbilt scores showed significant improvement for subjects with mGluR Tier 1 variants (P < 0.035). There were no differences in the incidence of adverse events between placebo week and weeks on active drug. The trial is registered at https://clinicaltrials.gov/ct2/show/study/NCT02286817 .
Volume
9
Issue
1
First Page
4
Last Page
4
ISSN
2041-1723
Published In/Presented At
Elia, J., Ungal, G., Kao, C., Ambrosini, A., De Jesus-Rosario, N., Larsen, L., Chiavacci, R., Wang, T., Kurian, C., Titchen, K., Sykes, B., Hwang, S., Kumar, B., Potts, J., Davis, J., Malatack, J., Slattery, E., Moorthy, G., Zuppa, A., Weller, A., … Hakonarson, H. (2018). Fasoracetam in adolescents with ADHD and glutamatergic gene network variants disrupting mGluR neurotransmitter signaling. Nature communications, 9(1), 4. https://doi.org/10.1038/s41467-017-02244-2
Disciplines
Medicine and Health Sciences
PubMedID
29339723
Department(s)
Department of Medicine
Document Type
Article