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J Neurodev Disord. 2017 Aug 2;9(1):26. doi: 10.1186/s11689-017-9207-8.

A randomized double-blind, placebo-controlled trial of ganaxolone in children and adolescents with fragile X syndrome.

Author information

1
Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California, Davis Medical Center, 2825 50th Street, Sacramento, CA, 95817, USA.
2
University of California, Davis School of Medicine, Sacramento, CA, USA.
3
Department of Medical Genetics, University of Antwerp, Antwerp, Belgium.
4
Department of Neurology-Pediatric Neurology, University Hospital Antwerp, University of Antwerp, Antwerp, Belgium.
5
Department of Medicine, University of California, Irvine School of Medicine, Orange, California, USA.
6
Biostatistics Institute for Clinical and Translational Science, University of California, Irvine, California, USA.
7
Seaver Autism Center for Research and Treatment, Department of Genetics and Genomic Sciences, Psychiatry, and Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
8
Department of Pediatrics, University of California, Davis Medical Center, Sacramento, CA, USA.
9
Department of Psychiatry and Behavioral Sciences, University of California, Davis Medical Center, Sacramento, CA, USA.
10
Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, Sacramento, CA, USA.
11
Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California, Davis Medical Center, 2825 50th Street, Sacramento, CA, 95817, USA. rjhagerman@ucdavis.edu.
12
Department of Pediatrics, University of California, Davis Medical Center, Sacramento, CA, USA. rjhagerman@ucdavis.edu.

Abstract

BACKGROUND:

Gamma-aminobutyric acid (GABA) system deficits are integral to the pathophysiologic development of fragile X syndrome (FXS). Ganaxolone, a GABAA receptor positive allosteric modulator, is hypothesized to improve symptoms such as anxiety, hyperactivity, and attention deficits in children with FXS.

METHODS:

This study was a randomized, double-blind, placebo-controlled, crossover trial of ganaxolone in children with FXS, aged 6-17 years.

RESULTS:

Sixty-one participants were assessed for eligibility, and 59 were randomized to the study. Fifty-five participants completed at least the first arm and were included in the intention-to-treat analysis; 51 participants completed both treatment arms. There were no statistically significant improvements observed on the primary outcome measure (Clinical Global Impression-Improvement), the key secondary outcome measure (Pediatric Anxiety Rating Scale-R), or any other secondary outcome measures in the overall study population. However, post-hoc analyses revealed positive trends in areas of anxiety, attention, and hyperactivity in participants with higher baseline anxiety and low full-scale IQ scores. No serious adverse events (AEs) occurred, although there was a significant increase in the frequency and severity of AEs related to ganaxolone compared to placebo.

CONCLUSIONS:

While ganaxolone was found to be safe, there were no significant improvements in the outcome measures in the overall study population. However, ganaxolone in subgroups of children with FXS, including those with higher anxiety or lower cognitive abilities, might have beneficial effects.

TRIAL REGISTRATION:

ClinicalTrials.gov, NCT01725152.

KEYWORDS:

Adolescents; Children; Clinical trial; Fragile X syndrome; Ganaxolone

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