Single-case experimental designs for bumetanide across neurodevelopmental disorders: BUDDI protocol.
Autism spectrum disorder
Bumetanide
Children
Neurodevelopmental disorders
Journal
BMC psychiatry
ISSN: 1471-244X
Titre abrégé: BMC Psychiatry
Pays: England
ID NLM: 100968559
Informations de publication
Date de publication:
07 07 2022
07 07 2022
Historique:
received:
03
12
2021
accepted:
01
06
2022
entrez:
7
7
2022
pubmed:
8
7
2022
medline:
12
7
2022
Statut:
epublish
Résumé
Bumetanide is a selective NKCC1 chloride importer antagonist which is being repurposed as a mechanism-based treatment for neurodevelopmental disorders (NDDs). Due to their specific actions, these kinds of interventions will only be effective in particular subsets of patients. To anticipate stratified application, we recently completed three bumetanide trials each focusing on different stratification strategies with the additional objective of deriving the most optimal endpoints. Here we publish the protocol of the post-trial access combined cohort study to confirm previous effects and stratification strategies in the trial cohorts and in new participants. Participants of the three previous cohorts and a new cohort will be subjected to 6 months bumetanide treatment using multiple baseline Single Case Experimental Designs. The primary outcome is the change, relative to baseline, in a set of patient reported outcome measures focused on direct and indirect effects of sensory processing difficulties. Secondary outcome measures include the conventional questionnaires 'social responsiveness scale', 'repetitive behavior scale', 'sensory profile' and 'aberrant behavior scale'. Resting-state EEG measurements will be performed at several time-points including at Tmax after the first administration. Assessment of cognitive endpoints will be conducted using the novel Emma Tool box, an in-house designed battery of computerized tests to measure neurocognitive functions in children. This study aims to replicate previously shown effects of bumetanide in NDD subpopulations, validate a recently proposed treatment prediction effect methodology and refine endpoint measurements. EudraCT: 2020-002196-35, registered 16 November 2020, https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-002196-35/NL.
Sections du résumé
BACKGROUND
Bumetanide is a selective NKCC1 chloride importer antagonist which is being repurposed as a mechanism-based treatment for neurodevelopmental disorders (NDDs). Due to their specific actions, these kinds of interventions will only be effective in particular subsets of patients. To anticipate stratified application, we recently completed three bumetanide trials each focusing on different stratification strategies with the additional objective of deriving the most optimal endpoints. Here we publish the protocol of the post-trial access combined cohort study to confirm previous effects and stratification strategies in the trial cohorts and in new participants.
METHOD/DESIGN
Participants of the three previous cohorts and a new cohort will be subjected to 6 months bumetanide treatment using multiple baseline Single Case Experimental Designs. The primary outcome is the change, relative to baseline, in a set of patient reported outcome measures focused on direct and indirect effects of sensory processing difficulties. Secondary outcome measures include the conventional questionnaires 'social responsiveness scale', 'repetitive behavior scale', 'sensory profile' and 'aberrant behavior scale'. Resting-state EEG measurements will be performed at several time-points including at Tmax after the first administration. Assessment of cognitive endpoints will be conducted using the novel Emma Tool box, an in-house designed battery of computerized tests to measure neurocognitive functions in children.
DISCUSSION
This study aims to replicate previously shown effects of bumetanide in NDD subpopulations, validate a recently proposed treatment prediction effect methodology and refine endpoint measurements.
TRIAL REGISTRATION
EudraCT: 2020-002196-35, registered 16 November 2020, https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-002196-35/NL.
Identifiants
pubmed: 35799144
doi: 10.1186/s12888-022-04033-8
pii: 10.1186/s12888-022-04033-8
pmc: PMC9260985
doi:
Substances chimiques
Bumetanide
0Y2S3XUQ5H
Types de publication
Clinical Trial Protocol
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
452Informations de copyright
© 2022. The Author(s).
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