Bumetanide for Core Symptoms of Autism Spectrum Disorder (BAMBI): A Single Center, Double-Blinded, Participant-Randomized, Placebo-Controlled, Phase-2 Superiority Trial.
J Am Acad Child Adolesc Psychiatry
; 60(7): 865-876, 2021 07.
Article
em En
| MEDLINE
| ID: mdl-32730977
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 11 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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transtorno Autístico
/
Transtorno do Espectro Autista
Tipo de estudo:
Clinical_trials
/
Diagnostic_studies
/
Prognostic_studies
Limite:
Child
/
Humans
País como assunto:
Europa
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article