E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
This study will assess the clinical efficacy of bumetanide using the most common behavioral endpoint scale in ASD trials to establish a first rational treatment concept in ASD that can be administered safely in children and adolescents.
Hypotheses
1. Thirteen weeks of treatment with bumetanide will effectively reduce ASD-related behavioral symptoms and improve day-to-day functioning in comparison with usual care.
2. Efficacy of bumetanide is associated with certain cognitive and psychophysiological parameters related to hyperexcitable networks in patients with ASD.
Objectives:
Primary aim: to investigate whether thirteen weeks treatment with bumetanide will improve daily life functioning and reduce behavioral symptoms in children with ASD in comparison with usual care.
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E.2.2 | Secondary objectives of the trial |
Secondary aim: to identify prognostic biomarkers of bumetanide treatment using cognitive and neurophysiological assessments.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Males or females aged ≥7 years to ≤15 years;
2. Criteria met for autism on Autism Diagnostic Observation Schedule - Generic (ADOS G) and Social Responsiveness Scale (SRS) (24).
3. Written informed consent.
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E.4 | Principal exclusion criteria |
1. Total IQ < 55 (WISC) and/or inability to comply with the protocol-specified procedures for the duration of the study, including treatment, blood sampling to control diuretic effects.
2. Serious, unstable illnesses including, gastroenterologic, respiratory, cardiovascular (QT interval lengthening), endocrinologic, immunologic, or hematologic disease;
3. Renal or hepatic dysfunction that would interfere with excretion or metabolism of Bumetanide;
4. Neurological disorders such as epilepsy, seizures and microcephaly;
5. Behavioral treatment
6. Treatment with psychoactive medications, including anticonvulsants, in the last 8 weeks prior to start of the study, except melatonin; no use of other psychoactive substances is allowed from 8 weeks prior to the pre-study evaluation until the endpoint measurements at the end of the washout period. If clinically feasible and desired by the patients and/or parents, then it is allowed to stop psychoactive medication to allow enrollment in the study after a 8 week washout period of their psychoactive medication.
7. Treatment with NSAIDS or aminoglycosides.
8. Documented history of hypersensitivity reaction to sulfonamide derivatives.
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E.5 End points |
E.5.1 | Primary end point(s) |
Social Responsiveness Scale (SRS) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Electroencephalogram (EEG)/ event-related potential (ERP) phenotypes, neurocognitive and other behavioral parameters. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Enrollment of 90 subjects. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |