Epileptic Encephalopathy with developmental delay MedDRA version: 20.0 Level: PT Classification code 10015039 Term: Epilepsy congenital System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 20.0 Level: SOC Classification code 10010331 Term: Congenital, familial and genetic disorders System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 20.0 Level: SOC Classification code 10029205 Term: Nervous system disorders System Orga
Conditions
Interventions
Product Name: fluoxetina
Product Code: [na]
Pharmaceutical Form: Tablet
CAS Number: 54910-89-3
Current Sponsor code: na
Other descriptive name: N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propan-1
Sponsors
AOU FEDERICO II
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Diagnosis of DEE with evidence of developmental delay associated with drug-resistant epilepsy as per ILAE criteria (ie failure to control epileptic activity despite the administration of two antiepileptic drugs appropriate for the condition in place) or diagnosis of autism spectrum disorder; Presence in genotypic analysis of mutations in genes coding for voltage-gated potassium channels KCNQ2, KCNQ3, KCNA1/2, KCNB1, KCNC1; Concentrations of antiepileptic drugs present in therapy that have already reached steady state at the time of recruitment. Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Infectious encephalitis, demyelinating or degenerative diseases of the central nervous system; - Pharmacological treatment with four or more antiepileptic drugs in combination, during the 60 days prior to enrollment in the study; - Treatment with the test drug during the 60 days prior to enrollment; - Presence of any clinical condition that represents a contraindication to the use of the drug that will be used for the trial (specifically, for all the molecules under study: hypersensitivity to the active ingredient, hepatic (AST, ALT, alkalyine phosphatase, gammaGT > 4 ULN) or renal insufficiency (KDOQI stage> III); for amitriptyline: the presence of convulsive pathology, congenital forms of long QT syndrome, glaucoma or obstructive pathologies of the urinary tract; for fampridine: the presence of convulsive pathology, the concomitant intake of drugs that block the OCT1 transporter such as cimetidine or quinidine; for fluoxetine: concomitant treatment with MAOIs or other drugs that interfere with serotonin uptake, presence of congenital forms of long QT syndrome; for gabapentine: the presence of pulmonary obstructive pathology or neuromuscular diseases and in particular myasthenia gravis; for metformin: any condition and increases the risk of lactic acidosis such as, in addition to liver and kidney failure, already mentioned as general contraindications, heart failure and acute or chronic ketoacidosis; - Participation in an ongoing clinical study involving the administration of any other experimental drug for the treatment of ED; - Uncooperative caregiver who does not ensure consistency and accuracy in keeping the epileptic seizures register, in the home administration of the drug or in the surveillance of the appearance of adverse events
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of the drugs gabapentine, fluoxetine, metformin, amitriptyline and fampridine in reducing seizure frequency in children with developmental and epileptic encephalopathy (DEE) respectively due to mutations in the potassium channels KCNQ2, KCNC1, KCNB1, KCNQ3 and KCNA1/2 whose sensitivity to these drugs has been ascertained in electrophysiological tests performed in vitro. To assess the efficacy of gabapentine, fluoxetine, metformin, amitriptyline and fampridine in improving behavioural disturbance, and in particular autism spectrum diroder phenotypes, in children affected by DEEs due to mutations in the potassium channels KCNQ2, KCNC1, KCNB1, KCNQ3 and KCNA1/2 whose sensitivity to these drugs has been ascertained in electrophysiological tests performed in vitro.;Secondary Objective: To evaluate the efficacy of the drugs gabapentine, fluoxetine, metformin, amitriptyline and fampridine in children with DEE due to mutations in the genes encoding for the potassium channels KCNQ2, KCNC1, KCNB1, KCNQ3 e KCNA1/2, respectively, whose sensitivity to said drugs has been ascertained in electrophysiological tests carried out in vitro: - in improving neurocognitive development - in improving body growth - in improving the quality of life of the patient and caregiver;Primary end point(s): Percentage change after 3 months of treatment in the number of epileptic seizures recorded by the caregiver over a 24-hour period as reported in a special diary with respect to the baseline values compared to entry into the study. - Percentage change after 3 months of treatment of the score measured on the assessment scales of the autism spectrum disorder ADOS-2, CARS-2 and Pep3 compared to the values measured upon entry into the study;Timepoint(s) of evaluation of this end point: Three months from the first day of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Percentage change in scores measured on the following neurocognitive development scales: Griffiths Mental Development Scales Extended Revised (GMDS-ER) and Child Behavior Checklist for ages 1 ½-5 by T. Achenbach and L. Rescoria. Percentage variations in auxological parameters (weight, height, head circumference) Percentage change in scores on the following scales of the patient's quality of life (measured with the PedsQL scale) and of the caregiver Caregiver Quality Of Life Questionnaire (Physical & Emotional) (CQLQ).;Timepoint(s) of evaluation of this end point: Three months from the first day of treatment | — |
Countries
Italy
Contacts
Public ContactUOC DI FARMACOLOGIA E TOSSICOLOGIA
AOU FEDERICO II
Outcome results
None listed