Nervous System Diseases

All Conditions

Symptoms and General Pathology

Neoplasms

Diseases and Abnormalities at or Before Birth

Skin and Connective Tissue Diseases

Rare Diseases

Epilepsy

Sclerosis

Seizures

Tuberous Sclerosis

Brain Diseases

Central Nervous System Diseases

Hamartoma

Neoplasms, Multiple Primary

Syndrome

Neoplastic Syndromes, Hereditary

Congenital Abnormalities

Malformations of Cortical Development

Nervous System Malformations

Neurocutaneous Syndromes

Heredodegenerative Disorders, Nervous System

Neurodegenerative Diseases

Genetic Diseases, Inborn

Tuberous Sclerosis Complex

infants that are seizure free at the time of the study enrollment and meets genetic or clinical diagnostic criteria for TSC

Parent or family guardian of infants that are seizure free at the time of the study enrollment and meets genetic or clinical diagnostic criteria for TSC.

Martina Bebin, MD

To determine whether EEGs during infancy is a reliable biomarker to identify TSC patients that will develop infantile spasms/epilepsy in the near future and thus are appropriate candidates for an antiepileptogenic drug trial. Since not all patients with TSC develop epilepsy, it would be useful to have a biomarker that could predict those patients destined to have epilepsy and thus identify those TSC patients most appropriate for an antiepileptogenic drug trial. A recent study suggests that treating TSC patients with an abnormal EEG prior to onset of infantile spasms with vigabatrin may improve neurological outcome, but the use of EEG as a reliable biomarker of future epilepsy has not been rigorously validated. In this specific aim, we will test the reliability of EEG in predicting future development of infantile spasms or epilepsy in TSC patients during the first year of life.

Current therapeutic approaches for epilepsy primarily represent symptomatic treatments that suppress seizures, but have not been demonstrated to prevent epilepsy or modify disease progression. In recent years, there have been tremendous interest and effort by basic scientists and clinicians in epilepsy in developing disease-modifying or "antiepileptogenic" therapies. However, these efforts are hindered by a couple significant limitations: 1) difficulty in identifying an appropriate high-risk patient population in which a preventative approach is feasible and justifiable, and 2) lack of appropriate drug targets with antiepileptogenic properties. Tuberous Sclerosis Complex (TSC) is one of the most common genetic causes of epilepsy and a subset of TSC patients may represent a rational, feasible population to target with an antiepileptogenic approach for several reasons. First of all, some patients are diagnosed with TSC at a young age before the onset of epilepsy due to non-neurological findings - thus, it is feasible to identify these patients and initiate a potential antiepileptogenic treatment at an early stage of epileptogenesis. Second, these patients are at high risk for developing epilepsy (\~80%) in the future, including infantile spasms (\~35%), a particularly devastating type of childhood epilepsy with a poor prognosis - thus, initiating a therapy with potential side effects in a pre-symptomatic stage can likely be justified in TSC patients. Finally, the identification of the mTOR pathway in the pathophysiology of TSC suggests that mTOR inhibitors could have antiepileptogenic properties in TSC, as already supported by pre-clinical animal studies - thus, a rational mechanistically-based treatment potentially already exists and can be readily tested in TSC patients. However, there may be significant risks and side effects of mTOR inhibitors, especially during early childhood, such as chronic immunosuppression and theoretical effects on learning, growth, and development. Thus, before initiating an antiepileptogenic drug trial in TSC patients, it would be beneficial to obtain further evidence to optimize the selection criteria and treatment paradigms to maximize efficacy and minimize side effects of mTOR inhibitors.

The aim of this clinical trial is to determine whether EEGs during infancy is a reliable biomarker to identify TSC patients that will develop infantile spasms/epilepsy in the near future and thus are appropriate candidates for an antiepileptogenic drug trial.

A single venous blood sample will be drawn from the child and parents/family guardian for future research studies and future genetic testing

Potential EEG Biomarkers and Antiepileptogenic Strategies for Epilepsy in TSC

Physical/neurological exam, Video EEG, Developmental assessments, Blood draw from child and parents/guardian, and Seizure diaries.

Children's Hospital Medical Center, Cincinnati

The University of Texas Health Science Center, Houston

University of California, Los Angeles

Boston Children's Hospital

University of Alabama at Birmingham

Associate Professor of Neurology

Hemangioma

Hemangioma, Capillary

Port-Wine Stain

Neoplasms, Vascular Tissue

Neoplasms by Histologic Type

Skin Abnormalities

Skin Diseases

Pharmaceutical Solutions

All Drugs and Chemicals

Anti-Arrhythmia Agents

Antihypertensive Agents

Vasodilator Agents

Propranolol

Adrenergic beta-Antagonists

Acebutolol

Adrenergic Agents

Adrenergic Antagonists

Neurotransmitter Agents

Sympathomimetics

Adrenergic beta-1 Receptor Antagonists

10 mg/kg/jour in 2 doses during 90 days after gradual increase of doses in the first week

3 mg/kg/jour in 3 doses during 90 days after gradual increase of doses in the first week

Propanolol

Michèle Bigorre, PH

There is no effective treatment for hemangioma regardless of immediate severity. That is in this respect a orphan disease. These hemangiomas, sometimes large, will have a phase of proliferation of several months (very scary for parents) and regression over several years. The natural history is peppered with local complications (ulcers) and aesthetic and psychological sequelae (sometimes major for the child and the family). The effects of acebutolol and propranolol on the proliferative hemangiomas were discovered accidentally by two French teams (Montpellier for acebutolol and Bordeaux for propranolol). Acebutolol and propranolol have been used for many years for the treatment of hypertension and congenital heart disease, including infants, with few side effects. The effects of acebutolol and propranolol were immediately visible with reduced volume and skin whitening of the hemangioma. In a preliminary study, acebutolol was administered to 20 patients in Montpellier with big regression of hemangiomas. The aim of the study was to compare the clinical efficacy of acebutolol (10mg/Kg/jour) and propranolol (3mg/Kg/j) on the proliferative phase of infantile hemangioma in infants.

Efficacy and Safety of Propranolol Versus Acebutolol on the Proliferative Phase of Infantile Hemangioma

It will be evaluated using a VAS (visual analogue scale) on a series of photos at Day 0, Day 30 and Day 90

All adverse events are collected at each visited

University Hospital, Montpellier

Musculoskeletal Diseases

Muscle Cramp

Spasm

Lennox Gastaut Syndrome

Spasms, Infantile

Epilepsies, Myoclonic

Neurologic Manifestations

Epilepsy, Generalized

Epileptic Syndromes

Dravet Syndrome

CDKL5 Deficiency Disorder

Lennox-Gastaut Syndrome

West Syndrome

Anticonvulsants

Cannabidiol

The 52-week treatment period includes a fixed 2-week titration schedule followed by flexible dose optimization.

Day 1: 5 mg/kg/day (2.5 mg/kg twice daily (b.i.d.))

Day 8: 10 mg/kg/day (5 mg/kg b.i.d.)

Day 15 to Week 52: Flexible dosing based on the participant's observed efficacy, safety, and tolerability per the investigator's clinical judgement. Up to a maximum of 20 mg/kg/day (10 mg/kg b.i.d.) for LGS and DS or 25 mg/kg/day (12.5 mg/kg b.i.d.) for TSC, in maximum weekly increments of 5 mg/kg/day (≤ 2.5 mg/kg b.i.d.).

GWP42003-P

Clinical Trial Disclosure & Transparency

This study will be conducted to evaluate the safety, pharmacokinetics (PK), and efficacy of adjunctive GWP42003-P in participants \< 2 years of age with tuberous sclerosis complex (TSC), Lennox-Gastaut syndrome (LGS), or Dravet syndrome (DS).

The study duration will be up to approximately 62 weeks, including a 4-week screening/baseline period, a 52-week dose optimization treatment period (which includes a fixed 2-week titration period followed by flexible dose optimization), a 10-day taper period, and a safety follow-up period (4 weeks after the end-of-taper visit).

Assessment of Adjunctive Cannabidiol Oral Solution (GWP42003-P) in Children With Tuberous Sclerosis Complex (TSC), Dravet Syndrome (DS), or Lennox-Gastaut Syndrome (LGS) Who Experience Inadequately-controlled Seizures

An Open-label, Single-arm Study to Assess the Safety, Pharmacokinetics, and Efficacy of Adjunctive Cannabidiol Oral Solution (GWP42003-P) in Participants With Tuberous Sclerosis Complex (Age 1 Month to < 2 Years of Age), Dravet Syndrome (1 Year to < 2 Years of Age), or Lennox-Gastaut Syndrome (1 Year to < 2 Years of Age) Who Experience Inadequately-controlled Seizures

The CGIC/S is a comprehensive neurodevelopmental assessment that covers the following domains: sensory, motor, cognition, emotional/behavioral health, communication, social, and adaptive functioning. This assessment is a 2-question survey per domain to be completed by the clinician. Individual domain scores will be summed and the total will be reported. Higher scores indicate poor clinical outcome.

The Infant and Toddler Quality of Life Questionnaire Short Form 47 (ITQOL-47) was developed for use in infants and toddlers from 12-months-to-5 years of age and assesses levels of health and well-being. The caregiver will complete the assessment on an electronic device. For each concept, item responses are scored, summed, and transformed on a scale from 0 (worst health) to 100 (best health). Higher scores indicate better clinical outcome.

Treatment Responders are defined as participants with ≥ 50% reduction from baseline in caregiver-reported total countable seizures

This endpoint includes the following changes in percentage of seizures:

* \> 25% (increase);
* ≥ 0% to ≤ 25% (increase);
* \> -25% to \< 0% (reduction);
* \> -50% to ≤ -25% (reduction);
* \> -75% to ≤ -50% (reduction);
* ≤ -75% (reduction).

Jazz Pharmaceuticals

Behaviors and Mental Disorders

Autistic Disorder

Autism Spectrum Disorder

Mustafa Sahin, MD, PhD

Darcy Krueger, MD, PhD

The investigators are enrolling 3-12 month old infants with a diagnosis of tuberous sclerosis complex (TSC) for a new study on early markers of autism. The study is looking for early signs for autism in a population (TSC) where autism is common. The goal of this project is to use behavioral testing, MRI and EEG techniques to identify children at risk for developing autism starting at 3 months of age and continuing until 36 months of age. Throughout the study, the investigators will recommend Early Intervention services for any child who shows early signs of autism.

This is a five-year multi-site study using MRI and EEG technologies to identify developmental precursors of Autism Spectrum Disorder in patients with Tuberous Sclerosis Complex (TSC). The study will be enrolling infants at five TSC centers throughout the country, including Boston Children's Hospital, Cincinnati Children's Hospital Medical Center, University of Alabama at Birmingham, University of Texas at Houston and University of California Los Angeles. The main goal of this study is to identify early signs of autism in children with TSC looking at the brain through MRI/diffusion tensor imaging, EEG and behavioral/neuropsychological methods. Eligible infants between the ages of 3-12 months will be evaluated longitudinally at regular visit intervals up to 3 years of age.

Study Objectives

1. To characterize the developmental precursors of ASD in a large number of TSC infants using a prospective multi-center design: Infants with TSC will be evaluated longitudinally at ages 3, 6, 9, 12, 18, 24 and 36 months. At each age, children will undergo standardized evaluations, using cognitive and adaptive measures. At age 24 and 36 months, formal assessment for autism will be performed. Clinical data including medication use, seizure history, EEG activity, genotypic variation, and co-morbidities will be recorded to determine if specific clinical factors modify the course of development.
2. To identify biomarkers with advanced diffusion tensor imaging (DTI) that help predict development of ASD in TSC infants: The investigators hypothesize that decreased white matter integrity performed annually for each of the first 3 years of life, including DTI sequences with tractography. Radial, axial, and mean diffusivity and fractional anisometry will be calculated for each time point and change over time correlated with development of ASD to determine relative risk. Individual measures at each time point will be compared between ASD and non-spectrum groups to assess the individual impact of each measure and timing.
3. To identify biomarkers with quantitative EEG that help predict development of ASD in TSC infants: The investigators hypothesize that altered functional connectivity, as measured by qEEG coherence and high frequency oscillations, will correlate with development of ASD in TSC. Quantitative EEG (qEEG), EEG coherence/gamma frequency (30-50Hz), and high frequency oscillations encompassing both ripples (80-250H) and fast ripples (250-500 Hz) will be measured at each time point. Changes over time will be correlated with development of ASD to determine relative risk, as will comparison of individual measures between the two groups. EEG findings will also be correlated with MR results obtained to further couple functional connectivity as measured by EEG with structural connectivity measured by DTI.

Early Biomarkers of Autism in Infants With Tuberous Sclerosis Complex (TSC)

Longitudinal Study to Identify Early Biomarkers of Autism Spectrum Disorder (ASD) in Infants With Tuberous Sclerosis Complex (TSC)

The ADOS performed at 24 and 36 months will be used as a preliminary diagnosis for data analysis. The primary outcome is the possible clinical diagnosis of autism spectrum disorder per the DSM 5 guidelines (Autistic Disorder, Asperger's and PDD-NOS).

MRI biomarkers obtained at baseline, 12, 24, 36 months will be applied to characterize individual patients in terms of brain tissue, white matter structure and connectivity, functional networks, and pathology. Brain tissue segmentation will be based on structural images derived from T1- and T2-weighted and FLAIR sequences using automated software tools designed for these tasks. White matter integrity and organization will be inferred from DTI imaging sequences. Structural connectivity networks will be delineated by DTI tractography assessment.

One-hour video-EEG containing both wakefulness and sleep (minimum of 20 minutes of each) will be obtained at baseline, 3, 6, 9, 12, 18, 24 and 36 months. Functional connectivity and pathological activity will be determined by measurement of EEG coherence and gamma frequency/high frequency oscillations.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Potential EEG Biomarkers and Antiepileptogenic Strategies for Epilepsy in TSC	NCT01767779	Tuberous Sclero...		1 Day - 6 Months	University of Alabama at Birmingham
Efficacy and Safety of Propranolol Versus Acebutolol on the Proliferative Phase of Infantile Hemangioma	NCT01743885	Hemangioma	Acebutolol Propanolol	- 6 Months	University Hospital, Montpellier
Potential EEG Biomarkers and Antiepileptogenic Strategies for Epilepsy in TSC	NCT01767779	Tuberous Sclero...		1 Day - 6 Months	University of Alabama at Birmingham
Assessment of Adjunctive Cannabidiol Oral Solution (GWP42003-P) in Children With Tuberous Sclerosis Complex (TSC), Dravet Syndrome (DS), or Lennox-Gastaut Syndrome (LGS) Who Experience Inadequately-controlled Seizures	NCT04485104	Seizure in Part... Seizure in Part... Seizure in Part...	GWP42003-P	1 Month - 23 Months	Jazz Pharmaceuticals
Early Biomarkers of Autism in Infants With Tuberous Sclerosis Complex (TSC)	NCT01780441	Tuberous Sclero...		3 Months - 12 Months	Boston Children's Hospital

Spots Global Cancer Trial Database for infants

Every month we try and update this database with for infants cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for infants

Every month we try and update this database with for infants cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for infants cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.