TY - JOUR
T1 - Bumetanide for Irritability in Children With Sensory Processing Problems Across Neurodevelopmental Disorders
T2 - A Pilot Randomized Controlled Trial
AU - van Andel, Dorinde M.
AU - Sprengers, Jan J.
AU - Keijzer-Veen, Mandy G.
AU - Schulp, Annelien J. A.
AU - Lillien, Marc R.
AU - Scheepers, Floortje E.
AU - Bruining, Hilgo
N1 - Funding Information: This study was supported by a grant from Dutch Brain Foundation (Hersenstichting #HA2015-01-04). This foundation had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript. Funding Information: We sincerely thank all the patients and their parents who participated in this study. We also thank the initial participating center Jonx Groningen for their efforts, time, and support and the UMCU research assistants (Gisela Timmer, Lisanne Geurts, and Demi Aarsman) for their assistance in recruitment, data collection, and their dedicated work. Publisher Copyright: Copyright © 2022 van Andel, Sprengers, Keijzer-Veen, Schulp, Lillien, Scheepers and Bruining.
PY - 2022/2/8
Y1 - 2022/2/8
N2 - Background: Treatment development for neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) is impeded by heterogeneity in clinical manifestation and underlying etiologies. Symptom traits such as aberrant sensory reactivity are present across NDDs and might reflect common mechanistic pathways. Here, we test the effectiveness of repurposing a drug candidate, bumetanide, on irritable behavior in a cross-disorder neurodevelopmental cohort defined by the presence of sensory reactivity problems. Methods: Participants, aged 5–15 years and IQ ≥ 55, with ASD, ADHD, and/or epilepsy and proven aberrant sensory reactivity according to deviant Sensory Profile scores were included. Participants were randomly allocated (1:1) to bumetanide (max 1 mg twice daily) or placebo tablets for 91 days followed by a 28-day wash-out period using permuted block design and minimization. Participants, parents, healthcare providers, and outcome assessors were blinded for treatment allocation. Primary outcome was the differences in ABC-irritability at day 91. Secondary outcomes were differences in SRS-2, RBS-R, SP-NL, BRIEF parent, BRIEF teacher at D91. Differences were analyzed in a modified intention-to-treat sample with linear mixed models and side effects in the intention-to-treat population. Results: A total of 38 participants (10.1 [SD 3.1] years) were enrolled between June 2017 and June 2019 in the Netherlands. Nineteen children were allocated to bumetanide and nineteen to placebo. Five patients discontinued (n = 3 bumetanide). Bumetanide was superior to placebo on the ABC-irritability [mean difference (MD) −4.78, 95%CI: −8.43 to −1.13, p = 0.0125]. No effects were found on secondary endpoints. No wash-out effects were found. Side effects were as expected: hypokalemia (p = 0.046) and increased diuresis (p = 0.020). Conclusion: Despite the results being underpowered, this study raises important recommendations for future cross-diagnostic trial designs.
AB - Background: Treatment development for neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) is impeded by heterogeneity in clinical manifestation and underlying etiologies. Symptom traits such as aberrant sensory reactivity are present across NDDs and might reflect common mechanistic pathways. Here, we test the effectiveness of repurposing a drug candidate, bumetanide, on irritable behavior in a cross-disorder neurodevelopmental cohort defined by the presence of sensory reactivity problems. Methods: Participants, aged 5–15 years and IQ ≥ 55, with ASD, ADHD, and/or epilepsy and proven aberrant sensory reactivity according to deviant Sensory Profile scores were included. Participants were randomly allocated (1:1) to bumetanide (max 1 mg twice daily) or placebo tablets for 91 days followed by a 28-day wash-out period using permuted block design and minimization. Participants, parents, healthcare providers, and outcome assessors were blinded for treatment allocation. Primary outcome was the differences in ABC-irritability at day 91. Secondary outcomes were differences in SRS-2, RBS-R, SP-NL, BRIEF parent, BRIEF teacher at D91. Differences were analyzed in a modified intention-to-treat sample with linear mixed models and side effects in the intention-to-treat population. Results: A total of 38 participants (10.1 [SD 3.1] years) were enrolled between June 2017 and June 2019 in the Netherlands. Nineteen children were allocated to bumetanide and nineteen to placebo. Five patients discontinued (n = 3 bumetanide). Bumetanide was superior to placebo on the ABC-irritability [mean difference (MD) −4.78, 95%CI: −8.43 to −1.13, p = 0.0125]. No effects were found on secondary endpoints. No wash-out effects were found. Side effects were as expected: hypokalemia (p = 0.046) and increased diuresis (p = 0.020). Conclusion: Despite the results being underpowered, this study raises important recommendations for future cross-diagnostic trial designs.
KW - ADHD
KW - ASD
KW - RCT
KW - bumetanide
KW - child
KW - epilepsy
KW - irritability
KW - sensory processing
UR - http://www.scopus.com/inward/record.url?scp=85125061997&partnerID=8YFLogxK
U2 - https://doi.org/10.3389/fpsyt.2022.780281
DO - https://doi.org/10.3389/fpsyt.2022.780281
M3 - Article
C2 - 35211042
SN - 1664-0640
VL - 13
JO - Frontiers in psychiatry
JF - Frontiers in psychiatry
M1 - 780281
ER -