Clinical trial NCT03715166: Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
Official title: A 6-month Randomised, Double-blind, Placebo Controlled Multicentre Parallel Group Study to Evaluate Efficacy and Safety of Bumetanide 0.5mg Twice a Day Followed by an Open Label Active 6-month Treatment Period With Bumetanide (0.5mg Twice a Day) and a 6 Weeks Discontinuation Period After Treatment Stop.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Autism Spectrum Disorder (ASD)
Lead sponsor: Servier
Sponsor class: INDUSTRY
Collaborators: name: ADIR, a Servier Group company
First posted: 2018-10-23
Enrollment: 211
Sex: ALL
Minimum age (years): 7
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 6-month, randomized, double-blind, placebo-controlled, parallel groups followed by an open label active 6-month treatment period with bumetanide.
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to evaluate the efficacy and the safety of bumetanide/S95008 in the improvement of Autism Spectrum Disorder core symptoms.

Detailed description: The present study (CL3-95008-001) was performed in children and adolescents from 7 to less than 18 years old presenting with ASD. A 6-month double-blind treatment period was performed in which efficacy and safety of bumetanide 0.5mg BID were assessed versus placebo. This double-blind period was followed by a 6-month open label treatment period of bumetanide 0.5mg BID in which long term safety was evaluated.

Eligibility criteria: Inclusion Criteria:

* Male and female patients from 7 to less than 18 years
* Out patients
* Primary diagnosis of ASD as per Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition (DSM-5) criteria
* Criteria met for ASD on Autism Diagnostic Observation Schedule (ADOS-2) and Autism Diagnosis Interview Revised (ADI-R)
* CGI (Clinical Global Impression) - Severity rating Score ≥ 4
* Childhood Autism Rating Scale second edition (CARS2-ST or HF) total raw score ≥ 34
* Social responsiveness Scale second edition total score (SRS-2 T-Score) ≥ 66
* Absence of known monogenic syndrome (Fragile X, Rett syndrome ...)
* Absence of any clinically significant abnormality likely to interfere with the conduct of the study according to the judgment of the investigator

Exclusion Criteria:

* Patients not able to follow the study assessments defined by the protocol, with the exception of self-rating questionnaires which will be assessed by parent/legal representative/caregiver for those patients unable to complete them
* Patients having a high suicidal risk according to the investigator judgement
* Chronic renal dysfunction
* Chronic cardiac dysfunction
* Patient with unstable psychotherapy, behavioural, cognitive or cognitive-behavioural therapy
* Severe electrolyte imbalance that is likely to interfere with the study conduct or evaluation

Primary outcomes:
measure: Childhood Autism Rating Scale, Second Edition (CARS2) total raw score
timeFrame: Change from baseline to 6 month
Secondary outcomes:
measure: Social Responsiveness Scale, Second Edition (SRS-2) total raw score
timeFrame: Change from baseline to 6 month
measure: Clinical Global Impression - Global Improvement (CGI-I) score
timeFrame: At 6 months
measure: Vineland Adaptative Behaviour Sales, Second Edition (VABS II) subscores
timeFrame: Change from baseline to 6 month
measure: Adverse events and Paediatric Adverse Event Rating Scale (PAERS)
timeFrame: On average of 52 weeks
measure: Abnormalities in 12-leads electrocardiogram (ECG) parameters
timeFrame: selection visit/Week004/Week008/Week012/Week 026/Week030/Week034/Week038/Week052
measure: Renal ultrasound
timeFrame: selection visit/Week026/Week052
measure: the Columbia Suicide Severity Rating Scale Children's version (C-SSRS-C)
timeFrame: Week000/Week012/Week026/Week038/Week052
measure: Tanner stage
timeFrame: Week000/Week026/Week052
measure: Acceptability and palatability questionnaire
timeFrame: Week026
measure: Paediatric Quality of Life Inventory (PedsQL) questionnaire
timeFrame: Week000/Week004/Week012/Week026/Week030/Week038/Week052
Other outcomes:
Locations:
city: Curitiba
country: Brazil
facility: Trial Tech em Pesquisas com Medicamentos Ltda
city: Fortaleza
country: Brazil
facility: Hospital Universitário Walter Cantídio - Universidade Federal do Ceará
city: Passo Fundo
country: Brazil
facility: Hospital São Vicente de Paulo
city: São Paulo
country: Brazil
facility: Universidade Federal de São Paulo, Escola Paulista de Medicina
city: São Paulo
country: Brazil
facility: Faculdade de Medicina da Universidade de São Paulo - Departamento de Psiquiatria
city: Nice
country: France
facility: GSC CHU-LENVAL Centre ressource autisme
state: Alpes-Maritimes
city: Strasbourg
country: France
facility: Hôpitaux Universitaires de Strasbourg Service de Psychiatrie de l'Enfant et de l'Adolescent
state: Alsace-Champagne-Ardenne-Lorraine
city: Bron
country: France
facility: Centre d'Investigation Clinique de Lyon
state: Auvergne Rhone Alpes
city: Bron
country: France
facility: Hôpital Le Vinatier CRA Rhône-Alpes, Bat 211
state: Auvergne-Rhône-Alpes
city: Paris
country: France
facility: Hôpital Robert Debré Service de Psychiatrie de l'enfant et de l'adolescent
state: Il De France
city: Rouen
country: France
facility: CHU Rouen
state: Normandie
city: Sotteville-lès-Rouen
country: France
facility: Centre Hospitalier du Rouvray Centre de Ressources pour l'Autisme
state: Normandie
city: Bordeaux
country: France
facility: Hôpital des Enfants-Pellegrin
state: Nouvelle Aquitaine
city: Bordeaux
country: France
facility: Centre Hospitalier Charles Perrens CRA Aquitaine
state: Nouvelle-Aquitaine
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg, Zentrum für Psychische Erkrankungen, Klinik für Psychiatrie, Psychotherapie und Psychosomatik im Kindes- und Jugendalter
state: Baden-Württemberg
city: Mannheim
country: Germany
facility: Klinik für Psychiatrie und Psychotherapie des Kindes- und Jugendalters am Zentralinstitut für Seelische Gesundheit
state: Baden-Württemberg
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus an der TU Dresden, Klinik und Poliklinik für Kinder- und Jugendpsychiatrie und
state: Saxony (Sachsen)
city: Budapest
country: Hungary
facility: Vadaskert Korhaz es Szakambulancia
city: Budapest
country: Hungary
facility: Servus Salvus Kft.
city: Gyula
country: Hungary
facility: Bekes Megyei Kozponti Korhaz Gyermek es ifjusagpszichiatriai osztaly
city: Szeged
country: Hungary
facility: Szegedi Tudományegyetem Szent-Gyorgy Albert Klinikai Kozpont Gyermekgyógyászati Klinika Gyermek es Ifjusagpszichiátriai o
city: Napoli
country: Italy
facility: Unità Semplice di Psichiatria Infantile Policlinico Universitario di Napoli - Università Federico II
state: Campania
city: Bosisio Parini
country: Italy
facility: Neuro Riabilitazione/Psicopatologia dell'età evolutiva Istituto Scientifico Medea - Bosisio Parini
state: Lombardia
city: Pavia
country: Italy
facility: U.O. di Neuropsichiatria Infantile Fondazione Istituto Neurologico Nazionale Casimiro Mondino Istituto di Ricovero e Cura a Carattere Scientifico
state: Lombardia
city: Cagliari
country: Italy
facility: Clinica di Neuropsichiatria dell'Infanzia e dell'Adolescenza Ospedale Pediatrico-Microcitemico
state: Sardegna
city: Messina
country: Italy
facility: Programma Interdipartimentale "Autismo 0-90" A.O.U. Policlinico "Gaetano Martino"
state: Sicilia
city: Calambrone
country: Italy
facility: U.O.C. Psichiatria dello Sviluppo IRCCS Fondazione Stella Maris
state: Toscana
city: Siena
country: Italy
facility: U.O. di Neuropsichiatria Infantile Azienda Ospedaliera Universitaria Senese
state: Toscana
city: Groningen
country: Netherlands
facility: Accare Groningen
city: Lodz
country: Poland
facility: NAVICULA Centrum Diagnozy i Terapii Autyzmu w Łodzi
state: Wojewodztwo Lodzkie
city: Warszawa
country: Poland
facility: Samodzielny Publiczny Dziecięcy Szpital Kliniczny w Warszawie Oddział Kliniczny Psychiatrii Wieku Rozwojowego
state: Wojewodztwo Mazowieckie
city: Gdansk
country: Poland
facility: Niepubliczny Zakład Opieki Zdrowotnej Gdańskie Centrum Zdrowia Sp. z o.o.
state: Wojewodztwo Pomorskie
city: Gdansk
country: Poland
facility: Centrum Badań Klinicznych PI-House sp. z o.o
city: Warszawa
country: Poland
facility: Fundacja SYNAPSIS ul.
city: Coimbra
country: Portugal
facility: Centro Hospitalar e Universitario de Coimbra Hospital Pediatrico
city: Terrassa
country: Spain
facility: Hospita Mutua de Terrassa
state: Barcelona
city: San Sebastian
country: Spain
facility: Policlinica Guipuzcoa
state: Guipuzcoa
city: Majadahonda
country: Spain
facility: Hospital Puerta de Hierro
state: Madrid
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Hospital Niño Jesus
city: Madrid
country: Spain
facility: Hospital Universitario Gregorio Marañon
city: Birmingham
country: United Kingdom
facility: Forward Thinking Birmingham_Birmingham Women's and Children's NHS Foundation Trust
city: London
country: United Kingdom
facility: ReCognition Health
city: Manchester
country: United Kingdom
facility: The Winnicott Centre
Study officials:
References:
citation: Fuentes J, Parellada M, Georgoula C, Oliveira G, Marret S, Crutel V, Albarran C, Lambert E, Penelaud PF, Ravel D, Ben Ari Y. Bumetanide oral solution for the treatment of children and adolescents with autism spectrum disorder: Results from two randomized phase III studies. Autism Res. 2023 Oct;16(10):2021-2034. doi: 10.1002/aur.3005. Epub 2023 Oct 4.