Behaviors and Mental Disorders

All Conditions

Neoplasms

Nervous System Diseases

Diseases and Abnormalities at or Before Birth

Symptoms and General Pathology

Skin and Connective Tissue Diseases

Rare Diseases

Autism Spectrum Disorder

Autistic Disorder

Neurofibromatoses

Neurofibromatosis 1

Neurofibroma

Child Development Disorders, Pervasive

Developmental Disabilities

Neurodevelopmental Disorders

Mental Disorders

Psychotic Disorders

Nerve Sheath Neoplasms

Neoplasms, Nerve Tissue

Neoplasms by Histologic Type

Syndrome

Neoplastic Syndromes, Hereditary

Neurocutaneous Syndromes

Heredodegenerative Disorders, Nervous System

Neurodegenerative Diseases

Genetic Diseases, Inborn

Peripheral Nervous System Diseases

Neuromuscular Diseases

Nervous System Neoplasms

Peripheral Nervous System Neoplasms

Neurofibromatosis

Neurofibromatosis Type 1

Lipid Regulating Agents

All Drugs and Chemicals

Lovastatin

L 647318

Dihydromevinolin

Anticholesteremic Agents

Hypolipidemic Agents

Antimetabolites

Hydroxymethylglutaryl-CoA Reductase Inhibitors

Enzyme Inhibitors

60 MG Lovastatin per day for 3 consecutive days

Lovastatin 60 MG

60 MG Placebo per day for 3 consecutive days

Placebos

Miguel S Castelo-Branco, MD, PhD

This study aims to investigate synaptic physiology and behavioral inhibition in patients with NF1 and ASD and to answer whether inhibitory deficits at these levels are modulated by lovastatin.

Structure: (1) Visit 1: Baseline assessment- participant's characterization, baseline outcome measures and additional evaluations, (2) 3 consecutive days of physiologically probing drug/placebo intake, (3) Visit 2: Outcome measures and additional evaluations in the day after the last drug/placebo intake, (4) Washout period of 4 to 6 weeks, (5) 3 consecutive days of drug/placebo intake, (6) Visit 3: Outcome measures and additional evaluations in the day after the last placebo/drug intake.

The literature has shown synaptic inhibitory dysfunction in both ASD and NF1. Here the investigators aim to test whether a mechanistic link can be established between that synaptic inhibitory dysfunction, systems levels changes in oscillatory synchrony and regulation of inhibition and treatment with Lovastatin in these two neurodevelopmental disorders. The investigators will explore this link through the application of complementary quantitative measures (putative biomarkers), such as magnetic resonance spectroscopy (MRS) transcranial magnetic stimulation (TMS) and electroencephalogram (EEG) applied to the same group of adult patients before and after the lovastatin or placebo intake during three days.

The intervention comprehends three sessions: the first two visits will occur in the same week and the third visit will take place 4 to 6 weeks later. In the first visit (baseline assessment), participants will perform neuropsychological, EEG, MRS and TMS assessment. In the other two visits participants will repeat EEG, MRS and TMS assessments to study possible post- intervention effects. Participants will intake 60mg of Lovastatin or Placebo during three consecutive days before the second and the third visits.

From Molecules to Cognition: Inhibitory Mechanisms in ASD and NF1

Linking Inhibition From Molecular to Systems and Cognitive Levels: a Preclinical and Clinical Approach in Autism Spectrum Disorders and Neurofibromatosis.

Comparing changes in brain excitation-inhibition measures (i.e., glutamate and GABA) when the GABAergic system is activated by oral dose of the Lovastatin 60mg during 3 days versus the placebo condition.

Amplitudes (mV) will be measured during stimulation of the primary motor cortex using transcranial magnetic stimulation

Periods (ms) will be measured during stimulation of the primary motor cortex using transcranial magnetic stimulation

Power (microV\^2) will be recorded during sensory stimulation using high density electroencephalography.

Amplitude (microV) will be recorded during sensory stimulation using high density electroencephalography.

University of Coimbra

Research Director of CIBIT-ICNAS

Nutritional and Metabolic Diseases

Migraine Disorders

Brain Neoplasms

Epilepsy

Drug Resistant Epilepsy

Metabolic Diseases

Brain Diseases

Central Nervous System Diseases

Quality of Life

Chronic Graft Versus Host Disease

Pediatric patients with any disease which require a ketogenic diet (KD), i.e. metabolic or genetic disorder or neurological (congenital and acquired) diseases

Patients recruited receive a ketogenic diet. The prescription, the type of KD protocol and the route of administration will depend, essentially, on the patient's ability and willingness to feed spontaneously and independently, as well as on compliance with the therapies set and the severity of the clinical conditions.

ketogenic diet (as per clinical practice)

Antonella Diamanti, MD

Sara Olivotto, MD

Roberto Previtali, MD

Valentina De Giorgis, MD

Carlo Alberto Quaranta, MD

The goal of this observational study is to learn about the clinical and nutritional effectiveness of ketogenic diet (KD) in pediatric patients with genetic, neurological or metabolic conditions requiring KD.

The main question\[s\] it aims to answer are:

* does KD support adequate growth?
* does KD improve clinical symptoms?
* how does KD impact quality of life? Participants will be followed up as per clinical practice

Scientific and clinical interest in KD is growing with a progressive increase in its therapeutic indications, ie recent studies show beneficial effects of KD in other diseases like migraine, autism spectrum disorder and brain tumors.

However, so far, the majority of results on KD effects have been collected in patients with drug-resistant epilepsy proving its effectiveness on clinical outcome (e.g. reducing epileptic seizures), frequently leaving out the nutritional assessment and the impact on quality of life. Nonetheless, these factors are indeed essential to ensure safety and efficacy of KD treatment, especially when dealing with children and in perspective of the progressive expansion of the target population that can benefit from this nutritional therapy.

The present multicenter study aims to analyse these poorly explored areas, by evaluating, in a cohort of pediatrics patient with indication to KD therapy, not only the KD effectiveness on the course of the underlying disease, but also the impact on nutritional parameters (e.g. growth, lipid profile, vitamin intake, bone mineral density, ..) and on quality of life.

Effectiveness and Impact on the Quality of Life of Ketogenic Diet in Pediatric Patients

Clinical and Nutritional Effectiveness and Impact on the Quality of Life of the Ketogenic Diet in Pediatric Patients With Neurological, Genetic or Metabolic Disorders: a Multicenter Prospective Observational Study

evaluate the nutritional adequacy of the diet after 6 months of treatment with ketogenic diet (KD) in terms of adequate growth defined by weight-for-age Z Score (WAZ) and length-for-age Z score (LAZ).

Evaluate the nutritional adequacy of the diet after 6 and 12 months of treatment with ketogenic diet (KD) in terms of correct growth defined by:

Weight-for-age Z-score (WAZ), length/height-for-age z-score (LAZ), BMI z-score Blood levels of selected parametres (eg cholesterol, HDL, LDL) within normal ranges Body composition (optional)

Evaluate the effectiveness of the ketogenic diet (KD) on the clinical outcomes (% of responders):

* Epilepsy: at least 50% seizure reduction after 6 months of KD treatment (vs 6 months before trial start( (daily diary records)
* ASD: reduction of at least 2-8 in CARS score after 6 months of KD treatment
* Chronic migraine: at least 50% episodes reduction after 6 months of KD treatment (vs 6 months before trial start( (daily diary records); reduction \>=50% of PedMiDas score after 6 months of KD treatment (vs baseline) Brain tumors: % survival; % of subjects with progression free survival

Evaluate the effectiveness of the ketogenic diet (KD) on the patient's quality of life using a non-validated questionnaire administered to parents with qualitative open and closed questions. Improvement will be considered as an improvement in the score of disease burden related questions baseline vs end of observation

Danone Nutricia SpA Società Benefit

Musculoskeletal Diseases

Heart and Blood Diseases

Blood and Lymph Conditions

Gland and Hormone Related Diseases

Sclerosis

Anxiety Disorders

Hyperkinesis

Phobia, Social

Impulsive Behavior

Fragile X Syndrome

Tourette Syndrome

Tics

Tic Disorders

Tuberous Sclerosis

Agoraphobia

DiGeorge Syndrome

22q11 Deletion Syndrome

Anxiety, Separation

Phobic Disorders

Ganglion Cysts

Synovial Cyst

Basal Ganglia Diseases

Movement Disorders

Intellectual Disability

Mental Retardation, X-Linked

Neurobehavioral Manifestations

Neurologic Manifestations

Chromosome Disorders

Sex Chromosome Disorders

Congenital Abnormalities

Genetic Diseases, X-Linked

Hamartoma

Neoplasms, Multiple Primary

Malformations of Cortical Development

Nervous System Malformations

Dyskinesias

Craniofacial Abnormalities

Musculoskeletal Abnormalities

Heart Defects, Congenital

Cardiovascular Abnormalities

Heart Diseases

Lymphatic Abnormalities

Lymphatic Diseases

Abnormalities, Multiple

Hypoparathyroidism

Parathyroid Diseases

Endocrine System Diseases

Tuberous Sclerosis Complex

22q11.2 Deletion Syndrome

Lymphatic Malformations

Psychotropic Drugs

Sertraline

Selective Serotonin Reuptake Inhibitors

Serotonin

Antidepressive Agents

Neurotransmitter Agents

Serotonin Receptor Agonists

Placebo

Karly Janisse

Paul Arnold

Francois Bolduc

Megan Thomas

Alessia Greco

Elisabetta Trinari

Ramona Rego

Sarosh Khalid-Khan

Baudouin Forgeot D'Arc

Evdokia Anagnostou

There are currently no approved medications for the treatment of anxiety in children and youth with neurodevelopmental disorders (NDDs), both common and rare. Sertraline, a selective serotonin reuptake inhibitor, has extensive evidence to support its use in children's and youth with anxiety but not within NDDs. More research is needed to confirm whether or not sertraline could help improve anxiety in children and youth with common and rare neurodevelopmental conditions. This is a pilot study, in which we plan to estimate the effect size of reduction in anxiety of sertraline vs. placebo. across rare and common neurodevelopmental disorders, and determine the best measure(s) to be used as a primary transdiagnostic outcome measure of anxiety, as well as diagnosis specific measures in future, larger-scale clinical trials of anxiety in NDDs.

Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders

A Randomized Placebo-Controlled Trial of Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders

The MASC-2 will be used as an additional anxiety measure to examine the effect of sertraline vs. placebo on measures of anxiety. The MASC-2 can be rated by parents or completed as a self-report. The parent rated version will be used and if the participant has adequate language ability, the self-report will also be used. The MASC-2 is a 50-item questionnaire. Each item is rated from 0 (Never) to 3 (Often). A higher score is indicative of higher symptoms of anxiety.

The CGI-S is a clinician reported scale which will be used to examine the effect of sertraline vs. placebo on measures of global function. The CGI-Severity Scale employs a seven point (1 = Normal, not at all ill to 7 = among the most extremely ill patients) to determine the participant's initial level of severity of impairment.

The SCARED is a 41-item measure of anxiety symptoms, with both child and parent versions. The Child version will be used as an exploratory outcome measure. The minimum overall score is 0 while the maximum overall score is 82. A score greater than or equal to 25 may indicate the presence of an Anxiety Disorder. Higher scores indicate a higher instance of anxiety symptoms while a lower score indicates a lower instance of anxiety symptoms.

The CGI-I is a clinician reported scale which will be used to examine the effect of sertraline vs. placebo on measures of global anxiety. The CGI-Improvement Scale employs a seven point (1 = very much improved to 7 = very much worse) to determine the participant's improvement in response to treatment.

The Parent Chief Complaint will be used to examine the effect of sertraline vs. placebo on individualized target symptoms. The objective of this measure is to have the parent describe the frequency and severity of one or two primary concerns of their child's behavior at the baseline visit and again at the end of treatment. Frequency is rated as Very Often (3), Often (2), Sometimes (1), or Rarely (0), and Severity is rated as Mild (1; behaviour occurs and is a mild problem), Moderate (2; behaviour occurs and is a moderate problem), and Severe (3; behaviour occurs and is a severe problem).

The PRAS-ASD will be used to examine the effect of sertraline vs. placebo on measures of anxiety in ASD. It is completed by the parents and includes 25 questions rated on a scale for 0-3 (none-severe problem).

The ADAMS is designed to assess anxiety and depression in children with and without intellectual disability. The ADAMS is a 28 item questionnaire which is rated by the parent. Each item is rated from 0 (behaviour has not occurred, or is not a problem) to 3 (behaviour occurs a lot, or is a severe problem).

The SCARED is a 41-item measure of anxiety symptoms, with both child and parent versions. The parent version will be used as a primary outcome measure. The minimum overall score is 0 while the maximum overall score is 82. A score greater than or equal to 25 may indicate the presence of an Anxiety Disorder. Higher scores indicate a higher instance of anxiety symptoms while a lower score indicates a lower instance of anxiety symptoms.

The CGI-I is a clinician reported scale which will be used to examine the effect of sertraline vs. placebo on measures of global function. The CGI-Improvement Scale employs a seven point (1 = very much improved to 7 = very much worse) to determine the participant's improvement in response to treatment.

The SMURF will be administered by the clinician at each visit to examine the safety and tolerability of sertraline. This rating covers a range of behavioural and physical AEs that are relevant to SSRIs.

The PedsQL will be used to examine the effect of sertraline vs. placebo on measures of quality of life. The PedsQL is measuring health-related quality of life (HRQOL) in 2- to 18-year-olds. The PedsQL 4.0 Generic Core Scales are multidimensional child self-report and parent-proxy report scales that have been used extensively as an outcome measure, including in ASD. We will use the parent-proxy report scale, and optionally, age-appropriate child self-report scale. Each item is is rated between a 0 (Never a problem) to 4 (Almost always a problem).

The HUI-3 will be used to examine the effect of sertraline vs. placebo on measures of general health status and health-related quality of life. The study is using the parent-proxy version of the HUI-3. The HUI-3 is a 15-item questionnaire to classify a subject's health status.

A whole blood serotonin assessment will be completed to examine the effect of sertraline vs. placebo on biomarkers of serotonin. 3mL of blood will be drawn at screening and week 16 visits for the purpose of this assessment. High performance liquid chromatography will be performed using fluorometric detection of 5-HT, tryptophan (TRP), and 5-hydroxyindole acetic acid (5-HIAA), using N-methylserotonin as an internal standard. Using this method, 5-HT intra- and inter- assay coefficients of variation are reliably less than 5% and 10%, respectively.

Azrieli Foundation

Canadian Institutes of Health Research (CIHR)

Ontario Brain Institute

Holland Bloorview Kids Rehabilitation Hospital

McMaster University

Western University

Queen's University

University of Alberta

Alberta Health services

St. Justine's Hospital

Dalhousie University

Unity Health Toronto

University of Toronto

The Hospital for Sick Children

Anagnostou, Evdokia, M.D.

Emergence Delirium

Psychomotor Agitation

Delirium

Central Nervous System Neoplasms

Confusion

Postoperative Complications

Neurocognitive Disorders

Pharmaceutical Solutions

Adjuvants, Anesthesia

Central Nervous System Depressants

Midazolam

50 patients premedicated with OZALIN® / OZASED®

50 patients who did not receive any premedication

Rossella Garra

The aim of this study was to assess the anxiolytic and sedative effect of OZALIN® / OZASED® (ADV6209) 0,25mg/Kg in children undergoing magnetic resonance imaging (MRI) under inhalational anesthesia. Our hypothesis is that compared to children who do not receive any premedication, palatability of OZALIN® / OZASED® by allowing an easier acceptance of the drug, improves the quality of anesthesia induction and postoperative behavioral outcome improving sedation and reducing the need for inhalation anesthetic which has been recognized as the main cause of post-procedural behavioral changes, including emergence agitation.

Magnetic resonance imaging is considered the primary investigative tool for evaluating a wide range of paediatric medical conditions. Sedatives are often needed in this population to ensure immobilization during the acquisition of the images.

Midazolam has always been the most used anxiolytic-sedative drug in the pediatric population. Over time, the intravenous formulation of midazolam has been used also for oral, nasal or rectal administration but those alternative routes of administration represent an off-label use. Recently, in Europe was licensed ADV6209, a midazolam solution for oral use containing gamma-cyclodextrin (OZALIN® / OZASED®).

The aim of this study was to assess its anxiolytic and sedative effect at a dosage of 0,25mg/Kg in children undergoing magnetic resonance imaging (MRI) under inhalational anesthesia. Our hypothesis is that compared to children who do not receive any premedication, palatability of OZALIN® / OZASED® by allowing an easier acceptance of the drug, improves the quality of anesthesia induction and postoperative behavioral outcome improving sedation and reducing the need for inhalation anesthetic which has been recognized as the main cause of post-procedural behavioral changes, including emergence agitation.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
From Molecules to Cognition: Inhibitory Mechanisms in ASD and NF1	NCT03826940	Autism Spectrum... Neurofibromatos...	Lovastatin 60 M... Placebos	16 Years - 65 Years	University of Coimbra
Effectiveness and Impact on the Quality of Life of Ketogenic Diet in Pediatric Patients	NCT06309251	Drug Resistant ... Autism Spectrum... Chronic Migrain... Brain Tumor, Pe...	ketogenic diet ...	- 18 Years	Danone Nutricia SpA Società Benefit
Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders	NCT06081348	Neurodevelopmen... Autism Autism Spectrum... Fragile X Syndr... Tuberous Sclero... 22Q11 Deletion ... 22Q11 Deletion ADHD Tic Disorders Tourette Syndro... Tourette Syndro... Tourette Syndro... ADHD - Combined... ADHD Predominan... ADHD, Predomina... Provisional Tic... Anxiety Anxiety Disorde... Agoraphobia Generalized Anx... Generalized Anx... Social Anxiety Social Anxiety ... Unspecified Anx... Other Specified... Separation Anxi...	Sertraline Placebo	8 Years - 17 Years	Anagnostou, Evdokia, M.D.
EMERGENCE AGITATION After Premedication IN PAEDIATRIC MAGNETIC RESONANCE IMAGING: A RETROSPECTIVE COHORT STUDY	NCT05946928	Autism Spectrum... Premedication Brain Neoplasms Brain Pathology Growth Retardat...		1 Year - 10 Years	Fondazione Policlinico Universitario Agostino Gemelli IRCCS
From Molecules to Cognition: Inhibitory Mechanisms in ASD and NF1	NCT03826940	Autism Spectrum... Neurofibromatos...	Lovastatin 60 M... Placebos	16 Years - 65 Years	University of Coimbra
From Molecules to Cognition: Inhibitory Mechanisms in ASD and NF1	NCT03826940	Autism Spectrum... Neurofibromatos...	Lovastatin 60 M... Placebos	16 Years - 65 Years	University of Coimbra

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