Symptoms and General Pathology

All Conditions

Behaviors and Mental Disorders

Neoplasms

Musculoskeletal Diseases

Nervous System Diseases

Diseases and Abnormalities at or Before Birth

Rare Diseases

Syndrome

Autistic Disorder

Hamartoma

Megalencephaly

Hamartoma Syndrome, Multiple

Autism Spectrum Disorder

Child Development Disorders, Pervasive

Developmental Disabilities

Neurodevelopmental Disorders

Mental Disorders

Psychotic Disorders

Neoplasms, Multiple Primary

Neoplastic Syndromes, Hereditary

Genetic Diseases, Inborn

Congenital Abnormalities

Craniofacial Abnormalities

Musculoskeletal Abnormalities

Malformations of Cortical Development

Nervous System Malformations

PTEN Hamartoma Tumor Syndrome

PTEN participants with Autism Spectrum Disorder group

PTEN participants without Autism Spectrum Disorder group

Rajna Filip-Dhima, MS

Jeff Anderson

Julian Martinez, MD, PhD

Robin Libove

Antonio Hardan, MD

Emine Arcasoy

Mustafa Sahin, MD, PhD

Adrienne Victory

David Ritter, MD

Beth Crouser

Charis Eng, MD, PhD

The purpose of this study is to determine cross-sectional and longitudinal medical, behavioral, and cognitive differences between PTEN ASD and other groups, as well as to identify cognitive, neural systems, and molecular biomarkers specific to PTEN ASD. In addition, this study will be creating and maintaining a biorepository and linked phenotypic database for PTEN ASD.

Autism spectrum disorders (ASD) are a set of neurodevelopmental disorders characterized by social communication/interaction impairments and restricted/repetitive behaviors. ASD associated with germline heterozygous PTEN mutations (PTEN ASD) is a genetically defined sub-group that, may be one of the more prevalent genetic disorders contributing to ASD (0.5-2%). The purpose of this research study is to carefully track the phenotypic and molecular characteristics of PTEN ASD and identify biomarkers for intervention studies.

Individuals with PTEN ASD, with macrocephalic ASD without a PTEN mutation (macro-ASD), healthy controls, and individuals with PTEN mutations without ASD (PTEN no-ASD) will be asked to participate in this study if they are 18 months and older. Both males and females will be asked to participate. Additionally, to be eligible for study participation, individuals' primary communicative language must be English.

The study involves 3 on site visits over the course of two years. Study visits will vary in length from about 4 hours to 6 hours. Study visits involve a physical exam, medical history questions, neuropsychological assessments, and a blood draw done for laboratory studies. A subset of participants between the ages of 2 and 11 years old will take part in the EEG portion of the study. Individuals who have a clinically indicated MRI will have an option to provide routine clinical scans for analysis.

Blood draw for future correlative studies in the PTEN Biorepository of the Developmental Synaptopathies Consortium.

170 subjects; 100 existing subjects, 70 newly enrolled participants; 50 controls

Natural History Study of Individuals With Autism and Germline Heterozygous PTEN Mutations

Verbal and non-verbal ability will be evaluated using Stanford Binet -5 or Mullen Scales of Early Learning (MSEL) at 12 months

Communication ability will be evaluated using composite score of the Peabody Picture Vocabulary Test (PPVT-4).

Communication ability will be evaluated using composite score of the Expressive Vocabulary Test (EVT-2) at 12 months.

Verbal and non-verbal ability will be evaluated using Stanford Binet 5 or Mullen Scales of Early Learning (MSEL) at 24 months

Visual perception will be measured using the Beery Developmental Test of Visuomotor Integration (VMI) at 12 months

Working memory will be evaluated using the Stanford Binet 5 at 12 months

Processing Speed will be measured using the Processing Speed Index from the Weschler Intelligence Scales at 12 months

Working memory will be evaluated using the Stanford Binet 5 at 24 months

Processing Speed will be measured using the Processing Speed Index from the Weschler Intelligence Scales at 24 months

Visual perception will be measured using the Beery Developmental Test of Visuomotor Integration (VMI) at 24 months

Communication ability will be evaluated using composite score of the Peabody Picture Vocabulary Test (PPVT-4) at 24 months

Communication ability will be evaluated using composite score of the Expressive Vocabulary Test (EVT-2) at 24 months.

National Institutes of Health (NIH)

National Institute of Neurological Disorders and Stroke (NINDS)

Office of Rare Diseases (ORD)

National Center for Advancing Translational Sciences (NCATS)

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Boston Children's Hospital

Assistant in NeurologyAssociate Professor of Neurology, Harvard Medical School

Skin and Connective Tissue Diseases

Sclerosis

Epilepsy

Tuberous Sclerosis

Neurocutaneous Syndromes

Heredodegenerative Disorders, Nervous System

Neurodegenerative Diseases

Tuberous Sclerosis Complex

The Treatment Group begins the JASPER intervention immediately upon enrollment in the study.

The Delayed treatment group receives the same JASPER intervention as the Treatment Group, but after 6 months of receiving services in the community as usual.

Participants who are unable to complete JASPER due to age or time/distance commitment can enroll for single-time point participation

JASPER (Joint Attention, Symbolic Play, Engagement, and Regulation) is a treatment approach based on a combination of developmental and behavioral principles developed by Dr. Connie Kasari and Dr. Amanda Gulsrud at UCLA. It targets the foundations of social communication (joint attention, imitation, play) and uses naturalistic strategies to increase the rate and complexity of social communication.

JASPER

Carly Hyde

Web:

Carly Hyde, BS

Jack Keller

Shafali Jeste

The investigators are running an intervention study for young children with Tuberous Sclerosis Complex (TSC). The study will include free play-based behavioral intervention administered remotely that may improve social and communication skills in children with TSC. Eligible families will have a child in the age range of 12-36 months, with a diagnosis of TSC. Children with TSC below 12 months may be eligible for an early markers study prior to enrollment in the intervention trial.

The intervention will focus on teaching caregivers skills to improve the social and communication outcomes of their children. The content of the intervention will be individually tailored to the child's developmental level. The intervention involves 4 on-site assessment visits, and 12 weekly intervention sessions, administered in-person and remotely. The intervention focuses on improving social-communication and play skills.

Tuberous Sclerosis Complex (TSC) is a genetic disorder caused by mutations in either the TSC1 or TSC2 genes. The genetic variation results in the growth of non-malignant tumors throughout the body. Neurodevelopmental disorders, including global developmental delay, intellectual disability, and autism spectrum disorder (ASD) are very common in children with TSC, although developmental outcomes can vary widely. Study investigators, over the past several years, has been studying infants and young children with TSC, and investigators have found that developmental delays can be identified in the first year of life, and that these delays and differences can predict a diagnosis of ASD. Currently, there is no specific treatment for the neurodevelopmental disorders associated with TSC. Based on this information, researchers now want to know if early intervention can help to improve development and prevent ASD in children with TSC.

Investigators are studying the effects of early behavioral intervention on developmental outcomes in infants and toddlers with TSC. The study focuses on social-communication skills, as these are tightly linked to the development of ASD. The overarching goal of this research is to improve outcomes in infants with TSC by conducting rigorous, innovative research in treatment, using both brain and behavioral measures to study the effects of treatment.

Participation requires four on-site assessment visits at UCLA or Boston Children's Hospital, and 12 weekly behavioral intervention sessions, administered in-person and remotely. Because this behavioral intervention is parent-mediated, a parent must be available to attend these sessions. Behavioral assessments generally take up to 4 hours to complete. This study also uses research EEG. This non-invasive assessment generally takes 30-45 minutes to complete. After the participant's first assessment, he/she will be randomly assigned to receive treatment either immediately or in 6 months, with behavioral assessments throughout. Participants will be involved in the study for a duration of 15-21 months, depending on randomization.

There are no anticipated risks from this study, although it is possible that the participant may react negatively to some of the assessment measures or intervention sessions. For example, at the most extreme, the participant may be fearful of an age-appropriate toy and may cry or physically pull back from the toy. If this should occur, that particular toy presentation, assessment or intervention will be stopped. Sometimes the EEG net can feel uncomfortable, especially if children do not like wearing hats or having anything touch their heads. Because of this, the study team will provide families with the demonstration ("practice") net to use with the participant before his/her session. At any time during the session if the participant becomes too upset or agitated, researchers will stop the session. Loss of confidentiality is a risk of participating in this research study. As described below, researchers will take every measure to keep participation in this research study confidential. Participants may benefit from the intervention by receiving detailed information about your child's cognitive, language, and communication skills both before the intervention begins and after the intervention is completed. Participants also may benefit from the intervention itself, which is aimed at improving social communication skills in infants and toddlers at high risk for neurodevelopmental disorders. Families will receive written feedback on the participants's performance on the behavioral assessments administered during assessment time point 4. These assessments are used for research purposes and therefore are not comprehensive clinical evaluations. Some of the assessments administered will measure social communication skills relevant to Autism Spectrum Disorder (ASD), and the feedback letter will report whether the assessment indicated the possible presence of ASD. The results of the research may also contribute to the broader TSC and autism fields by enhancing the knowledge of the effects of early intervention on social communication skills in TSC. Benefits that participating children may derive from the intervention may lead to greater benefits for all children with autism and/or TSC.

JASPER Early Intervention for Tuberous Sclerosis

Mechanisms of Change With Early Intervention in Tuberous Sclerosis

Change from baseline in the amount of time spent in a Joint Attention (the coordination of attention between objects and people for the purpose of sharing) state at 3 months; ESCS is an experimental measure reported as frequency for requesting and joint attention in 15-minute intervals

Change from baseline in the amount of time spent in a Joint Attention (the coordination of attention between objects and people for the purpose of sharing) state at 6 months; ESCS is an experimental measure reported as frequency for requesting and joint attention in 15-minute intervals

change from baseline in Joint Engagement (shared engagement in a play routine) at 3 months into study participation, according to the parent caregiver interaction assessment.

change from baseline in Joint Engagement (shared engagement in a play routine) at 6 months into study participation, according to the parent caregiver interaction assessment.

Change from baseline in Symbolic Play (types of play and level of play) at 3 months; this is an experimental measure reported as types of behaviors reflecting flexibility and diversity of the child's play level, based on distinct sets of toys that target specific developmental markers of play.

Change from baseline in Symbolic Play (types of play and level of play) at 6 months; this is an experimental measure reported as types of behaviors reflecting flexibility and diversity of the child's play level, based on distinct sets of toys that target specific developmental markers of play.

Measures cognitive ability and language development (baseline to 3 months). The test has five scales: gross motor, visual reception, fine motor, receptive language, and expressive language. The test identifies the subject's strengths and weaknesses and assesses early intellectual development.

Measures cognitive ability and language development (baseline to 6 months). The test has five scales: gross motor, visual reception, fine motor, receptive language, and expressive language. The test identifies the subject's strengths and weaknesses and assesses early intellectual development.

Change from baseline at 3 months in the amount of Parent use of social communication support strategies Parent use of social communication support strategies as taught by JASPER will be measured by a parent-child interaction assessment.

Massachusetts General Hospital

University of California, Los Angeles

Director of Developmental Neurophysiology Lab

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.

Tuberous Sclerosis Alliance

MD, PhD

Intellectual Disability

Neurobehavioral Manifestations

Neurologic Manifestations

Jessica Krefting, RN

Martina Bebin, MD

Angela Martinez

Rajsekar Rajaraman, MD

Jeilo Gauna

Brenda Porter, MD

Molly Griffith

Mariam Lugo Noguera

Hope Northrup, MD

The purpose of this study is to characterize the developmental phenotype of ASD and ID and to identify biomarkers using advanced MRI methodology and electrophysiological biomarkers of synaptic function and connectivity predictive of ASD and ID presence and severity in patients with TSC. In addition, this study will be establishing infrastructure for the collection and storage of human bio-specimens, including genetic material, from TSC patients and their family members with ASD.

Tuberous Sclerosis Complex (TSC) is a multi-system disease that usually exhibits a high variability in clinical findings both among and within families. About 50% of individuals with TSC develop intellectual disability (ID) and/or autism spectrum disorder (ASD). The purpose of this research study is to learn more information about ASD/ID in individuals with TSC through neurobehavioral assessments, electroencephalogram (EEG) data, and magnetic resonance imaging so that ultimately effective treatments and interventions for ASD/ID can be realized.

Individuals with TSC will be asked to participate in this study if they are 18 months or older at the time of enrollment and have been diagnosed with suspected or confirmed autism spectrum disorder and/or intellectual disability, as well as healthy controls. Both males and females will be asked to participate. Additionally, to be eligible for study participation, individuals' primary communicative language must be English. The participant and at least one biological parent will be asked to provide biological specimens including DNA and RNA for inclusion in the TSC RDCRN Biorepository.

The study involves 3 on site visits over the course of two years. Study visits will vary in length from about 4 hours to 6 hours. Study visits involve a physical exam, medical history questions, and neuropsychological assessments. A subset of participants between the ages of 2 and 11 years old will take part in the EEG portion of the study. At one point during the study, a blood draw will be done for future research studies. Individuals who have a clinically indicated MRI will have an option to provide routine clinical scans for analysis.

Blood draw for future correlative studies in the TSC Biorepository of the Developmental Synaptopathies Consortium.

Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)

Using standardized composite score for ADOS-2 performed yearly to determine ASD

Using standardized IQ score from the Stanford-Binet Intelligence Scales Fifth Edition (SBIS-5) or Mullen Scales of Early Learning (MSEL) performed yearly to determine ID

To determine cerebellum white matter structural integrity, the primary outcome measures will be fractional anisotropy (FA) determined by MRI diffusion tensor imaging (DTI) with tractography at 12 months radial diffusivity (RD), axial diffusivity (AD), and mean diffusivity (MD) of cerebellar fascicles corresponding to the neuroanatomically-defined excitatory and inhibitory projections cerebellar Purkinje neurons,

To determine cerebellum white matter structural integrity, the primary outcome measures will be fractional anisotropy (FA) determined by MRI diffusion tensor imaging (DTI) with tractography at 24 months

To determine cerebellum white matter structural integrity, the primary outcome measures will be radial diffusivity (RD) determined by MRI diffusion tensor imaging (DTI) with tractography at 12 months

To determine cerebellum white matter structural integrity, the primary outcome measures will be radial diffusivity (RD) determined by MRI diffusion tensor imaging (DTI) with tractography at 24 months

To determine cerebellum white matter structural integrity, the primary outcome measures will be mean diffusivity (MD) of cerebellar fascicles determined by MRI diffusion tensor imaging (DTI) with tractography at 12 months

To determine cerebellum white matter structural integrity, the primary outcome measures will be mean diffusivity (MD) of cerebellar fascicles determined by MRI diffusion tensor imaging (DTI) with tractography at 24 months

To determine cerebellum white matter structural integrity, the primary outcome measures will be axial diffusivity (AD) determined by MRI diffusion tensor imaging (DTI) with tractography at 12 months

To determine cerebellum white matter structural integrity, the primary outcome measures will be axial diffusivity (AD) determined by MRI diffusion tensor imaging (DTI) with tractography at 24 months

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Natural History Study of Individuals With Autism and Germline Heterozygous PTEN Mutations	NCT02461446	PTEN ASD Autism Macrocephaly PTEN Hamartoma ...		18 Months -	Boston Children's Hospital
JASPER Early Intervention for Tuberous Sclerosis	NCT03422367	Tuberous Sclero...	JASPER	6 Months - 40 Months	University of California, Los Angeles
JASPER Early Intervention for Tuberous Sclerosis	NCT03422367	Tuberous Sclero...	JASPER	6 Months - 40 Months	University of California, Los Angeles
Early Biomarkers of Autism in Infants With Tuberous Sclerosis Complex (TSC)	NCT01780441	Tuberous Sclero...		3 Months - 12 Months	Boston Children's Hospital
Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)	NCT02461459	Tuberous Sclero... Autism Disorder Intellectual Di...		18 Months -	Boston Children's Hospital

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Spots Global Cancer Trial Database for asd

Every month we try and update this database with for asd 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 asd 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.