Evaluation of the Efficiency of Treatment by BUMETANIDE on Autistic Children With a Known Ethiology (BUMAUTEP)

Evaluation of the Efficiency of Treatment by BUMETANIDE on Autistic Children With a Known Ethiology : Multicenter and Double Blind-study With Randomized Parallel Group, Against Placebo.

During a previous therapeutic trial, investigators showed that the bumetanide improved significantly autism. This trial showed that a therapeutic response was obtained in 75% of cases.

These first results were reinforced by a study led with adult patients for whom the eye tracking measurements as well as the functional MRI showed a diminution of the response time and a modification (amplification) of the cerebral response during an emotions recognition test.

Finally, investigators confirmed the physiological mechanism behind the action of the bumetanide in a study in two mouse models of autism.

Study Overview

• Status: Withdrawn
• Conditions: Autistic Disorder
• Intervention / Treatment: Drug: Bumetanide; Drug: Placebo

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 15 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Children and teenager from age 5 to age 17, with a diagnosis of typical autism or Asperger syndrome according to the criteria of diagnosis of the WHO's classification (CIM-10),
• With a known etiology,
• Patients for whom the CARS results are strictly Superior or equal to 30,
• Of whom the parents have given their free, informed and written consent,
• Affiliated or beneficiary of the French social security.

Exclusion Criteria:

• Patients under treatment by inlet diuretic either at the time of the study or before,
• Patients with electrolytic disorders,
• Patients with a known hypersensitivity to sulfa drugs,
• Patients with a hepatic or renal failure,
• Patients with an epilepsy not controlled by a treatment (comitial crisis in the past 6 month at the time the trial starts despite a treatment),
• Patients under treatment by psychotropic exception made of the melatonin,
• Allergy to the bumetanide or one of its excipients,
• Patient under a treatment by lithium, diphemanil, erythromycin IV, halofantrine, pentamidine, sultopride, vincamine, aminoglycoside,
• Pregnant and lactating women.

Secondary exclusion criteria:

• QT prolongation noticed on the ECG at Day0,
• Anomaly on the biological check up (Day 0) made before including the patient that would contraindicated the prescription of bumetanide,
• Patients for whom the CARS results are strictly inferior to 30.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bumetanide group; During 3 months in the double blind, the patient will receive the experimental treatment. For the patient of 25kg and more the bumetanide is used at the posology of 1mg in the morning and 1mg in the evening, for patient under 25kg the posology is 0.5mg in the morning and 0.5mg in the evening. After the 3 months in the double blind trial (bumetanide versus placebo), all the patient will receive (in the open phase of the trial) the bumetanide during 3 months with the posology fitting with their weights.	Drug: Bumetanide; For the patient of 25kg and more the bumetanide is used at the posology of 1mg in the morning and 1mg in the evening, for patient under 25kg the posology is 0.5mg in the morning and 0.5mg in the evening.
Placebo Comparator: Placebo group; During 3 months in the double blind, the patient will receive the placebo. For the patient of 25kg and more the bumetanide is used at the posology of 1mg in the morning and 1mg in the evening, for patient under 25kg the posology is 0.5mg in the morning and 0.5mg in the evening. After the 3 months in the double blind trial (bumetanide versus placebo), all the patient will receive (in the open phase of the trial) the bumetanide during 3 months with the posology fitting with their weights.	Drug: Placebo; For the patient of 25kg and more the placebo is used at the posology of 1mg in the morning and 1mg in the evening, for patient under 25kg the posology is 0.5mg in the morning and 0.5mg in the evening.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change (evolution) between day 0 and day 99 of the result of the scale CARS (Childhood Autism Rating Scale).	Day 0 and Day 99

Secondary Outcome Measures

Outcome Measure	Time Frame
CARS (Childhood Autism Rating Scale) between D0 and D99 and between D99 and D190 which will be describe by etiology	Day 0, Day 99 and Day 190

Collaborators and Investigators

• Sponsor: University Hospital, Limoges

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Actual): December 1, 2019
• Study Completion (Actual): June 1, 2020

Study Registration Dates

• First Submitted: October 25, 2016
• First Submitted That Met QC Criteria: October 27, 2016
• First Posted (Estimate): October 28, 2016

Study Record Updates

• Last Update Posted (Actual): June 2, 2021
• Last Update Submitted That Met QC Criteria: June 1, 2021
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: autism, Bumetanide
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder; Autistic Disorder; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Sodium Potassium Chloride Symporter Inhibitors; Bumetanide
• Other Study ID Numbers: I14039