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Cited by 97Autism Spectrum Disorder ResearchGenetics and Neurodevelopmental DisordersChild Nutrition and Feeding Issues

Bumetanide for core symptoms of autism spectrum disorder (BAMBI): a single center, double-blinded, participant-randomized, placebo-controlled, phase-2 superiority trial

Open access
Sprengers, Jan J., van Andel, Dorinde M., Zuithoff, Nicolaas P.A., Keijzer-Veen, Mandy G., Schulp, Annelien J.A., Scheepers, Floortje E., Lilien, Marc R., Oranje, Bob +1 more·2021·Journal of the American Academy of Child & Adolescent Psychiatry
DOI 10.1016/j.jaac.2020.07.888
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Abstract

OBJECTIVE: Recent trials have indicated positive effects of bumetanide in autism spectrum disorder (ASD). We tested efficacy of bumetanide on core symptom domains using a single center, parallel-group, participant-randomized, double-blind, placebo-controlled phase-2 superiority trial in a tertiary hospital in the Netherlands. METHOD: Unmedicated children aged 7 to 15 years with ASD and IQ ≥55 were block-randomized 1:1 to oral-solution bumetanide versus placebo, titrated to a maximum of 1.0 mg twice daily for 91 days (D91), followed by a 28-day wash-out period. The primary outcome was difference in Social Responsiveness Scale-2 (SRS-2) total score at D91, analyzed by modified intention-to-treat with linear mixed models. RESULTS: A total of 92 participants (mean age 10.5 [SD 2.4] years) enrolled between June 2016 and December 2018. In all, 47 children were allocated to bumetanide and 45 to placebo. Two participants dropped out per treatment arm. After 91 days, bumetanide was not superior to placebo on the primary outcome, the SRS-2 (mean difference -3.16, 95% CI = -9.68 to 3.37, p = .338). A superior effect was found on one of the secondary outcomes, the Repetitive Behavior Scale-Revised (mean difference -4.16, 95% CI = -8.06 to -0.25, p = .0375), but not on the Sensory Profile (mean difference 5.64, 95% CI = -11.30 to 22.57, p = .508) or the Aberrant Behavior Checklist Irritability Subscale (mean difference -0.65, 95% CI = -2.83 to 1.52, p = .552). No significant wash-out effect was observed. Significant adverse effects were predominantly diuretic effects (orthostatic hypotension (17 [36%] versus 5 [11%], p = .007); hypokalemia (24 [51%] versus 0 [0%], p < .0001), the occurrence of which did not statistically influence treatment outcome. CONCLUSION: The trial outcome was negative in terms of no superior effect on the primary outcome. The secondary outcomes suggest efficacy on repetitive behavior symptoms for a subset of patients. CLINICAL TRIAL REGISTRATION INFORMATION: Bumetanide in Autism Medication and Biomarker Study (BAMBI); https://www.clinicaltrialsregister.eu/; 2014-001560-35.

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  • A recent double-blind, placebo-controlled, phase 2 superiority trial in children with ASD without severe intellectual disability did not show any treatment benefits on the core symptoms of ASD as measured on the SRS-2.

    “However, a recent double-blind, placebo-controlled, phase 2 superiority trial in children with ASD without severe intellectual disability did not show any treatment benefits on the core symptoms of ASD as measured on the SRS-2 [97].”

    From An Update on Psychopharmacological Treatment of Autism Spectrum Disorder (2022) · cites this paper as [97]

  • The same trial showed treatment benefits on the repetitive behavior scale, with no major adverse effects.

    “It did show treatment benefits on the repetitive behavior scale, with no major adverse effects.”

    From An Update on Psychopharmacological Treatment of Autism Spectrum Disorder (2022) · cites this paper as [97]

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Authors
Sprengers, J. J., van Andel, D. M., Zuithoff, N. P. A., Keijzer-Veen, M. G., Schulp, A. J. A., Scheepers, F. E., Lilien, M. R., Oranje, B., & Bruining, H.
Affiliations
University Medical Center Utrecht (NL)
Corresponding author
Bruining, Hilgo
ORCID
Venue
Journal of the American Academy of Child & Adolescent Psychiatry
Publisher
Elsevier BV
Published
2021-07
Volume
60
Issue
7
Pages
865-876
ISSN
0890-8567 (ISSN-L)
DOI
10.1016/j.jaac.2020.07.888
OpenAlex
W3045998212
Semantic Scholar
273d149fdb8d1d2f9dcac83c0e06db74a99bf3ab
Cited by
97
References
44
Citations by year
2026: 6 · 2025: 9 · 2024: 15 · 2023: 17 · 2022: 23 · 2021: 22 · 2020: 4 · 2014: 1
FWCI
8.86
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of the American Academy of Child & Adolescent Psychiatry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Pure Amsterdam UMC (publishedVersion, other-oa)
  • Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
  • Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
Funders
ZonMw (836041015)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Health Sciences › Medicine › Psychiatry and Mental health › Child Nutrition and Feeding Issues
Keywords
bumetanide, autism spectrum disorder, core symptoms, social responsiveness, repetitive behavior, sensory processing, irritability, diuretic adverse effects, orthostatic hypotension, hypokalemia, children and adolescents, sensory profile
MeSH terms
Autism Spectrum Disorder, Autistic Disorder, Bumetanide, Child, Double-Blind Method, Humans, Membrane Proteins, Netherlands, Treatment Outcome

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