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An open-label study evaluating the safety, behavioral, and electrophysiological outcomes of low-dose ketamine in children with ADNP syndrome.

Alexander Kolevzon, Tess Levy, Sarah Barkley, Sandra Bedrosian-Sermone, Matthew H. Davis, Jennifer Foss-Feig, Danielle Halpern, Katherine Keller, Ana Kostic, Christina Layton, Rebecca Lee, Bonnie Lerman, Matthew Might, Sven Sandin, Paige M Siper, Laura G Sloofman, Hannah Walker, Jessica Zweifach, Joseph D. Buxbaum

HGG advances October 13, 2022 DOI: 10.1016/j.xhgg.2022.100138 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Open-label, single-dose pilot trial Pilot study Peer reviewed
Sample size 10
Population Children with ADNP syndrome ages 6 to 12 years
Intervention Ketamine
Dose 0.5 mg/kg infused intravenously over 40 min
Duration Single-dose administration with assessments one week after administration
Measures Clinical Global Impressions - Improvement scale, auditory steady-state response, computerized eye tracking
Topics Ketamine Esketamine
Keywords Adnp Asd Autism spectrum disorder
Key findings A single low-dose ketamine infusion was generally well tolerated in ten children with ADNP syndrome, with no serious adverse events. One week after treatment, parent- and clinician-rated measures showed nominally significant improvements across social behavior, attention-deficit/hyperactivity, restricted and repetitive behaviors, and sensory sensitivities. The authors describe these results as preliminary and hypothesis generating, cautioning that the small sample size and absence of a placebo control limit interpretation.

Abstract

Activity-dependent neuroprotective protein (ADNP) syndrome is a rare genetic condition associated with intellectual disability and autism spectrum disorder. Preclinical evidence suggests that low-dose ketamine may induce expression of ADNP and that neuroprotective effects of ketamine may be mediated by ADNP. The goal of the proposed research was to evaluate the safety, tolerability, and behavioral outcomes of low-dose ketamine in children with ADNP syndrome. We also sought to explore the feasibility of using electrophysiological markers of auditory steady-state response and computerized eye tracking to assess biomarker sensitivity to treatment. This study utilized a single-dose (0.5 mg/kg), open-label design, with ketamine infused intravenously over 40 min. Ten children with ADNP syndrome ages 6 to 12 years were enrolled. Ketamine was generally well tolerated, and there were no serious adverse events. The most common adverse events were elation/silliness (50%), fatigue (40%), and increased aggression (40%). Using parent-report instruments to assess treatment effects, ketamine was associated with nominally significant improvement in a wide array of domains, including social behavior, attention deficit and hyperactivity, restricted and repetitive behaviors, and sensory sensitivities, a week after administration. Results derived from clinician-rated assessments aligned with findings from the parent reports. Overall, nominal improvement was evident based on the Clinical Global Impressions - Improvement scale, in addition to clinician-based scales reflecting key domains of social communication, attention deficit and hyperactivity, restricted and repetitive behaviors, speech, thinking, and learning, activities of daily living, and sensory sensitivities. Results also highlight the potential utility of electrophysiological measurement of auditory steady-state response and eye-tracking to index change with ketamine treatment. Findings are intended to be hypothesis generating and provide preliminary support for the safety and efficacy of ketamine in ADNP syndrome in addition to identifying useful endpoints for a ketamine clinical development program. However, results must be interpreted with caution given limitations of this study, most importantly the small sample size and absence of a placebo-control group.

Comparable studies

Other non-randomized and open-label trials on ketamine, most cited first.

Study Year Design Participants
Rapid Resolution of Suicidal Ideation After a Single Infusion of anN-Methyl-D-Aspartate Antagonist in Patients With Treatment-Resistant Major Depressive Disorder Subjects with DSM-IV-diagnosed treatment-resistant major depressive disorder 2010 Open-label trial n = 33
Intravenous arketamine for treatment-resistant depression: open-label pilot study Humans with treatment-resistant depression 2020 Open-label pilot trial n = 7
A Phase 2 Open Label Study of Efficacy, Safety, and Tolerability of SLS-002 (Intranasal Racemic Ketamine) in Adults with MDD at Imminent Risk of Suicide. Hospitalized patients with Major Depressive Disorder and acute suicidal ideation and... 2024 Open label study n = 17
Ketamine Psychedelic Therapy (KPT): A Review of the Results of Ten Years of Research Alcoholic patients 1997 Controlled clinical trial n = 211
Ketamine Safety and Tolerability in Clinical Trials for Treatment-Resistant Depression Participants with DSM-IV-defined major depressive disorder and treatment-resistant... 2014 Pooled analysis of three clinical trials n = 97

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