<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03758521</url>
  </required_header>
  <id_info>
    <org_study_id>IRB-P00029917</org_study_id>
    <secondary_id>1R01HD091142-01A1</secondary_id>
    <nct_id>NCT03758521</nct_id>
  </id_info>
  <brief_title>Natural History Study of Patients With Succinic Semialdehyde Dehydrogenase (SSADH) Deficiency</brief_title>
  <official_title>Natural History Study of Patients With Succinic Semialdehyde Dehydrogenase (SSADH) Deficiency</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boston Children's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Washington State University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of South Florida</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital Heidelberg</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Boston Children's Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Succinic Semialdehyde Dehydrogenase deficiency (SSADHD) is a rare autosomal recessive disease&#xD;
      that interferes with the catabolism of the major inhibitory neurotransmitter gamma-amino&#xD;
      butyric acid (GABA) and furthermore leads to accumulation of various potential toxic&#xD;
      metabolites, most prominently gamma hydroxybutyric acid (GHB). Current research indicates&#xD;
      that there is developmental delay and significant neurophysiological and biochemical&#xD;
      alterations in SSADHD patients, but whether disease presentation varies with age is not&#xD;
      known. The investigators propose to determine the natural course of the clinical presentation&#xD;
      of SSADHD; to determine the natural course of neurophysiological and biochemical indices&#xD;
      known to be altered in SSADHD; and to identify neurophysiological and biochemical predictors&#xD;
      of clinical severity.&#xD;
&#xD;
      The overall objective is to define the natural course of the clinical, neurophysiological and&#xD;
      biochemical spectrum of SSADHD. Secondary objectives include the identification of biomarkers&#xD;
      that correlate with disease phenotype and predict clinical outcomes, and the creation of an&#xD;
      international SSADHD data repository for future investigation of pathogenesis and therapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study will be conducted by 4 academic institutions: Washington State University (WSU),&#xD;
      Boston Children's Hospital (BCH), University of South Florida (USF), and University&#xD;
      Children's Hospital Heidelberg (iNTD). The design of the study is mixed, with longitudinal&#xD;
      and cross-sectional assessments over a period of 5 years.&#xD;
&#xD;
      Patients will be separated into three cohorts. The Boston Children's cohort will be a total&#xD;
      of 20 patients evaluated at Boston Children's Hospital in the United States. These patients&#xD;
      will be followed for five years, and attend a visit to the hospital in years 1,3 and 5 where&#xD;
      assessments including history/physical, neuropsychological testing, EEG, TMS, and&#xD;
      bio-specimen collection will be completed. Each patient will have an MRI of the brain done&#xD;
      with special GABA sequencing one time over the five years. Each visit will take place over&#xD;
      the course of two days. At BCH, the goal will be to schedule visits every other year with&#xD;
      questionnaires and surveys sent out up to every 6 months, and bio-specimen collection every&#xD;
      year. The BCH team will also ask for two follow up phone calls occurring 12 months after each&#xD;
      onsite visit. Visits will consist of clinical assessments (demographics, medical history,&#xD;
      physical examination, neurological exam, medication history, neuropsychological assessments,&#xD;
      and clinical severity score), neurophysiological assessments (Brain MRI/MRS/DTI,&#xD;
      Electroencephalogram, and Transcranial magnetic stimulation), and yearly bio-specimen&#xD;
      collection (blood, urine, saliva, hair, stool, and skin biopsy). Bio-specimens will be sent&#xD;
      to Washington State University for testing and addition to a biorepository. The iNTD&#xD;
      (international NeuroTransmitters Disorders) cohort will be comprised of 15 patients who are&#xD;
      seen at European sites who will have approval through their ethics committee to share&#xD;
      de-identified information. Bio-specimens will be attempted to be collected at each visit from&#xD;
      patients and sent to Washington State University. At the iNTD sites and for patients followed&#xD;
      outside of iNTD, visits and bio-specimen collections will depend on the patients' follow-up&#xD;
      schedules with electronic, web-based survey sent on a regular schedule (every 6 months). The&#xD;
      standard of care cohort will be comprised of 10 patients throughout the world who provide&#xD;
      consent to share de-identified information to the database.&#xD;
&#xD;
      The data will be stored in a database on the University of South Florida server. The server&#xD;
      is password protected, and each member of the study personal will have a unique log in to&#xD;
      have access to the site. Subjects will also be given specialized access to complete follow up&#xD;
      electronic web based surveys twice a year over the course of 5 years. The team at USF will&#xD;
      assist with data analysis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 15, 2019</start_date>
  <completion_date type="Anticipated">June 2024</completion_date>
  <primary_completion_date type="Anticipated">May 31, 2024</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Clinical Severity Score</measure>
    <time_frame>5 Years</time_frame>
    <description>A composite score ranging from 5 (profound impairment) to 25 (no impairment) will be calculated using scores from five clinically significant subdomains (cognition, communication, motor skills, psychiatric presentation, and epilepsy), each scored from 1 (worse) to 5 (no impairment).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Biochemical - GABA measurement</measure>
    <time_frame>5 Years</time_frame>
    <description>GABA is measured by electron-capture negative-ion mass fragmentography. The level will be measured in the different bio-specimens.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Biochemical - GHB measurement</measure>
    <time_frame>5 Years</time_frame>
    <description>GHB is measured using gas chromatography-mass spectrometry (GCMS). GHB will be measured in the different bio-specimens.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Quantification of GABA related signals on the MRI spectroscopy</measure>
    <time_frame>5 Years</time_frame>
    <description>MRI spectroscopy with special editing for GABA-related peaks in multi-voxel MRS. Concentrations will be analyzed.</description>
  </primary_outcome>
  <other_outcome>
    <measure>Quantification of EEG abnormalities (%)</measure>
    <time_frame>5 Years</time_frame>
    <description>Degree of epileptiform abnormalities will be recorded using the American Clinical Neurophysiology Society guidelines [Continuous (&gt;90%), Abundant (50-89%), Frequent (10-49%), Occasional (1-9%), and Rare (&lt; 1 %)].</description>
  </other_outcome>
  <other_outcome>
    <measure>Extent of altered signal hyperintensities on structural MRI (%)</measure>
    <time_frame>5 years</time_frame>
    <description>Altered T2 and FLAIR signal hyperintensities will be reported as a percent.</description>
  </other_outcome>
  <other_outcome>
    <measure>Degree of myelination on structural MRI (%)</measure>
    <time_frame>5 years</time_frame>
    <description>Degree of myelination will be reported as a percent.</description>
  </other_outcome>
  <other_outcome>
    <measure>Total cerebral volume on structural MRI (cm3)</measure>
    <time_frame>5 years</time_frame>
    <description>Total cerebral volume will be reported in cubic centimeters (cm3).</description>
  </other_outcome>
  <other_outcome>
    <measure>Amplitudes of motor evoked potentials (mm)</measure>
    <time_frame>5 years</time_frame>
    <description>Intracortical Inhibition (ICI) and Facilitation (ICF) are a paired-pulse TMS measure of cortical excitability. A short Interval interstimuli (2ms) leads to a cortical inhibition, which reflects the GABAergic neurotransmission; whereas a longer interval interstimuli leads to a cortical facilitation, which reflects glutamatergic neurotransmission. Analyzed by obtaining peak-to-peak amplitudes in millimeters (mm).</description>
  </other_outcome>
  <other_outcome>
    <measure>Durations of cortical silent period (ms)</measure>
    <time_frame>5 years</time_frame>
    <description>Cortical Silent Period (CSP) is a single-pulse TMS measure of cortical inhibition, stimulations are applied while subjects are exerting a muscular contraction and lead to a muscular cancellation. Duration of this silence is measured in milliseconds (ms).</description>
  </other_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Anticipated">55</enrollment>
  <condition>Succinic Semialdehyde Dehydrogenase Deficiency</condition>
  <arm_group>
    <arm_group_label>BCH Cohort</arm_group_label>
    <description>Patients enrolled at BCH will travel to BCH every 2 years at a minimum for comprehensive evaluation taking place over a 48 hour period. Visits to BCH may occur within ± 2 months of the scheduled visit date. Electronic surveys will be sent out every 6 months.Visits will consist of clinical assessments (demographics, medical history, physical examination, neurological exam, medication history, neuropsychological assessments, and clinical severity score), neurophysiological assessments (Brain Magnetic resonance imaging [MRI/MRS/DTI], Electroencephalogram [EEG], and Transcranial magnetic stimulation [TMS]), and yearly bio-specimen collection.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>iNTD Cohort</arm_group_label>
    <description>Patients enrolled at iNTD sites will travel to their iNTD site according to standard of care requirements. Data collection includes clinical history and relevant laboratory-chemical, therapeutic, instrumental and neuropsychological parameters by the study centers. Data collection takes place within the framework of elective outpatient visits. The collected parameters are congruent with the current standard investigations. Electronic surveys will be sent out every 6 months. Imaging and neurophysiological data will be collected if performed during the clinical visit or if performed as part of the site's ongoing research. Yearly bio-specimen collection will be attempted after consent is obtained from the family.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard of Care Cohort</arm_group_label>
    <description>Patients enrolled at other sites will attend their visit at their regular clinical site as mandated by standard of care. Data collection includes medical history, family history, medications, and all clinical and neuropsychological assessments listed. Imaging and neurophysiological data will be collected if performed during the clinical visit or if performed as part of the clinical site's ongoing research. Yearly bio-specimen collection will be attempted.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Transcranial magnetic stimulation (TMS)</intervention_name>
    <description>Transcranial magnetic stimulation (TMS) is a method for noninvasive electrical cortical stimulation, where small intracranial currents are generated by a powerful, fluctuating, extracranial magnetic field. TMS is unique in its capacity for experimental, diagnostic, and therapeutic utility. Single pulse (spTMS) and paired-pulse TMS (ppTMS) have been used extensively to study, measure, and modulate cortical excitability and plasticity.</description>
    <arm_group_label>BCH Cohort</arm_group_label>
    <other_name>Nexstim Navigated Brain Stimulation (NBS) System 4</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Magnetic resonance imaging (MRI)</intervention_name>
    <description>These will be outpatient MRI studies that are planned without sedation. Subjects enrolled at BCH will undergo brain MRI, including volumetric MRI, MRS, and diffusion tensor imaging (DTI). The data will help define the natural history of brain volume, brain myelination and spectroscopic (e.g. GABA) abnormalities.</description>
    <arm_group_label>BCH Cohort</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Electroencephalogram (EEG)</intervention_name>
    <description>These will be outpatient EEG recordings that span 20-60 minutes and done without sedation. Recordings will be performed using electrode locations specified by the international 10-20 system for standard clinical practice.</description>
    <arm_group_label>BCH Cohort</arm_group_label>
    <other_name>Natus</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Bio-specimen Collection</intervention_name>
    <description>Bio-specimen collection will include blood, urine, saliva, hair, stool, and a skin biopsy. Blood, urine, saliva, blood spots, and hair samples will also be banked for to-be-determined (TBD) studies.</description>
    <arm_group_label>BCH Cohort</arm_group_label>
    <arm_group_label>Standard of Care Cohort</arm_group_label>
    <arm_group_label>iNTD Cohort</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Bio-specimen collection will include blood, urine, saliva, hair, stool, and a skin biopsy.&#xD;
      Blood, urine, saliva, blood spots, and hair samples will also be banked for to-be-determined&#xD;
      (TBD) studies.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Children and adults diagnosed with Succinic Semialdehyde Dehydrogenase (SSADH) deficiency.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  4-hydroxybutyric aciduria (γ-hydroxybutyric aciduria)&#xD;
&#xD;
          -  documented pathogenic ALDH5A1 (aldehyde dehydrogenase 5A1 gene) mutation&#xD;
&#xD;
          -  0-99 years&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  active or recent substance abuse or dependence within the past year.&#xD;
&#xD;
          -  inability to participate in the study procedures.&#xD;
&#xD;
          -  any condition that makes the study subject, in the opinion of the investigator,&#xD;
             unsuitable for the study.&#xD;
&#xD;
          -  patients will be excluded from the MRI section of the study if they have: implanted&#xD;
             cardiac pacemaker or autodefibrillators, implanted neural pacemakers, cochlear&#xD;
             implants, metallic foreign bodies in the eye or Central Nervous System (CNS), any&#xD;
             implanted wire or metal device that may concentrate radio frequency fields.&#xD;
&#xD;
          -  patients less than age two years will be excluded from the TMS procedure.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Phillip L Pearl, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Boston Children's Hospital/Harvard Medical School</affiliation>
  </overall_official>
  <overall_official>
    <last_name>K. Michael Gibson, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Washington State University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Boston Children's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Children's Hospital</name>
      <address>
        <city>Heidelberg</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sant Joan de Deu Hospital Barcelona</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Birmingham Children's Hospital NHS Foundation Trust</name>
      <address>
        <city>Birmingham</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
    <country>Spain</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>November 16, 2018</study_first_submitted>
  <study_first_submitted_qc>November 28, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 29, 2018</study_first_posted>
  <last_update_submitted>July 17, 2023</last_update_submitted>
  <last_update_submitted_qc>July 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 19, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Boston Children's Hospital</investigator_affiliation>
    <investigator_full_name>Phillip Pearl</investigator_full_name>
    <investigator_title>Director of Epilepsy and Clinical Neurophysiology, William G. Lennox Chair, Boston Children's Hospital</investigator_title>
  </responsible_party>
  <keyword>SSADHD</keyword>
  <keyword>SSADH deficiency</keyword>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03758521
org study id: IRB-P00029917
secondary id: 1R01HD091142-01A1
nct id: NCT03758521
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Succinic Semialdehyde Dehydrogenase deficiency (SSADHD) is a rare autosomal recessive disease
      that interferes with the catabolism of the major inhibitory neurotransmitter gamma-amino
      butyric acid (GABA) and furthermore leads to accumulation of various potential toxic
      metabolites, most prominently gamma hydroxybutyric acid (GHB). Current research indicates
      that there is developmental delay and significant neurophysiological and biochemical
      alterations in SSADHD patients, but whether disease presentation varies with age is not
      known. The investigators propose to determine the natural course of the clinical presentation
      of SSADHD; to determine the natural course of neurophysiological and biochemical indices
      known to be altered in SSADHD; and to identify neurophysiological and biochemical predictors
      of clinical severity.

      The overall objective is to define the natural course of the clinical, neurophysiological and
      biochemical spectrum of SSADHD. Secondary objectives include the identification of biomarkers
      that correlate with disease phenotype and predict clinical outcomes, and the creation of an
      international SSADHD data repository for future investigation of pathogenesis and therapy.
The study will be conducted by 4 academic institutions: Washington State University (WSU),
      Boston Children's Hospital (BCH), University of South Florida (USF), and University
      Children's Hospital Heidelberg (iNTD). The design of the study is mixed, with longitudinal
      and cross-sectional assessments over a period of 5 years.

      Patients will be separated into three cohorts. The Boston Children's cohort will be a total
      of 20 patients evaluated at Boston Children's Hospital in the United States. These patients
      will be followed for five years, and attend a visit to the hospital in years 1,3 and 5 where
      assessments including history/physical, neuropsychological testing, EEG, TMS, and
      bio-specimen collection will be completed. Each patient will have an MRI of the brain done
      with special GABA sequencing one time over the five years. Each visit will take place over
      the course of two days. At BCH, the goal will be to schedule visits every other year with
      questionnaires and surveys sent out up to every 6 months, and bio-specimen collection every
      year. The BCH team will also ask for two follow up phone calls occurring 12 months after each
      onsite visit. Visits will consist of clinical assessments (demographics, medical history,
      physical examination, neurological exam, medication history, neuropsychological assessments,
      and clinical severity score), neurophysiological assessments (Brain MRI/MRS/DTI,
      Electroencephalogram, and Transcranial magnetic stimulation), and yearly bio-specimen
      collection (blood, urine, saliva, hair, stool, and skin biopsy). Bio-specimens will be sent
      to Washington State University for testing and addition to a biorepository. The iNTD
      (international NeuroTransmitters Disorders) cohort will be comprised of 15 patients who are
      seen at European sites who will have approval through their ethics committee to share
      de-identified information. Bio-specimens will be attempted to be collected at each visit from
      patients and sent to Washington State University. At the iNTD sites and for patients followed
      outside of iNTD, visits and bio-specimen collections will depend on the patients' follow-up
      schedules with electronic, web-based survey sent on a regular schedule (every 6 months). The
      standard of care cohort will be comprised of 10 patients throughout the world who provide
      consent to share de-identified information to the database.

      The data will be stored in a database on the University of South Florida server. The server
      is password protected, and each member of the study personal will have a unique log in to
      have access to the site. Subjects will also be given specialized access to complete follow up
      electronic web based surveys twice a year over the course of 5 years. The team at USF will
      assist with data analysis.
observational model: Cohort
time perspective: Prospective
measure: Clinical Severity Score
time frame: 5 Years
description: A composite score ranging from 5 (profound impairment) to 25 (no impairment) will be calculated using scores from five clinically significant subdomains (cognition, communication, motor skills, psychiatric presentation, and epilepsy), each scored from 1 (worse) to 5 (no impairment).
measure: Biochemical - GABA measurement
time frame: 5 Years
description: GABA is measured by electron-capture negative-ion mass fragmentography. The level will be measured in the different bio-specimens.
measure: Biochemical - GHB measurement
time frame: 5 Years
description: GHB is measured using gas chromatography-mass spectrometry (GCMS). GHB will be measured in the different bio-specimens.
measure: Quantification of GABA related signals on the MRI spectroscopy
time frame: 5 Years
description: MRI spectroscopy with special editing for GABA-related peaks in multi-voxel MRS. Concentrations will be analyzed.
measure: Quantification of EEG abnormalities (%)
time frame: 5 Years
description: Degree of epileptiform abnormalities will be recorded using the American Clinical Neurophysiology Society guidelines [Continuous (>90%), Abundant (50-89%), Frequent (10-49%), Occasional (1-9%), and Rare (< 1 %)].
measure: Extent of altered signal hyperintensities on structural MRI (%)
time frame: 5 years
description: Altered T2 and FLAIR signal hyperintensities will be reported as a percent.
measure: Degree of myelination on structural MRI (%)
time frame: 5 years
description: Degree of myelination will be reported as a percent.
measure: Total cerebral volume on structural MRI (cm3)
time frame: 5 years
description: Total cerebral volume will be reported in cubic centimeters (cm3).
measure: Amplitudes of motor evoked potentials (mm)
time frame: 5 years
description: Intracortical Inhibition (ICI) and Facilitation (ICF) are a paired-pulse TMS measure of cortical excitability. A short Interval interstimuli (2ms) leads to a cortical inhibition, which reflects the GABAergic neurotransmission; whereas a longer interval interstimuli leads to a cortical facilitation, which reflects glutamatergic neurotransmission. Analyzed by obtaining peak-to-peak amplitudes in millimeters (mm).
measure: Durations of cortical silent period (ms)
time frame: 5 years
description: Cortical Silent Period (CSP) is a single-pulse TMS measure of cortical inhibition, stimulations are applied while subjects are exerting a muscular contraction and lead to a muscular cancellation. Duration of this silence is measured in milliseconds (ms).
arm group label: BCH Cohort
description: Patients enrolled at BCH will travel to BCH every 2 years at a minimum for comprehensive evaluation taking place over a 48 hour period. Visits to BCH may occur within ± 2 months of the scheduled visit date. Electronic surveys will be sent out every 6 months.Visits will consist of clinical assessments (demographics, medical history, physical examination, neurological exam, medication history, neuropsychological assessments, and clinical severity score), neurophysiological assessments (Brain Magnetic resonance imaging [MRI/MRS/DTI], Electroencephalogram [EEG], and Transcranial magnetic stimulation [TMS]), and yearly bio-specimen collection.
arm group label: iNTD Cohort
description: Patients enrolled at iNTD sites will travel to their iNTD site according to standard of care requirements. Data collection includes clinical history and relevant laboratory-chemical, therapeutic, instrumental and neuropsychological parameters by the study centers. Data collection takes place within the framework of elective outpatient visits. The collected parameters are congruent with the current standard investigations. Electronic surveys will be sent out every 6 months. Imaging and neurophysiological data will be collected if performed during the clinical visit or if performed as part of the site's ongoing research. Yearly bio-specimen collection will be attempted after consent is obtained from the family.
arm group label: Standard of Care Cohort
description: Patients enrolled at other sites will attend their visit at their regular clinical site as mandated by standard of care. Data collection includes medical history, family history, medications, and all clinical and neuropsychological assessments listed. Imaging and neurophysiological data will be collected if performed during the clinical visit or if performed as part of the clinical site's ongoing research. Yearly bio-specimen collection will be attempted.
intervention type: Device
intervention name: Transcranial magnetic stimulation (TMS)
description: Transcranial magnetic stimulation (TMS) is a method for noninvasive electrical cortical stimulation, where small intracranial currents are generated by a powerful, fluctuating, extracranial magnetic field. TMS is unique in its capacity for experimental, diagnostic, and therapeutic utility. Single pulse (spTMS) and paired-pulse TMS (ppTMS) have been used extensively to study, measure, and modulate cortical excitability and plasticity.
arm group label: BCH Cohort
other name: Nexstim Navigated Brain Stimulation (NBS) System 4
intervention type: Device
intervention name: Magnetic resonance imaging (MRI)
description: These will be outpatient MRI studies that are planned without sedation. Subjects enrolled at BCH will undergo brain MRI, including volumetric MRI, MRS, and diffusion tensor imaging (DTI). The data will help define the natural history of brain volume, brain myelination and spectroscopic (e.g. GABA) abnormalities.
arm group label: BCH Cohort
intervention type: Device
intervention name: Electroencephalogram (EEG)
description: These will be outpatient EEG recordings that span 20-60 minutes and done without sedation. Recordings will be performed using electrode locations specified by the international 10-20 system for standard clinical practice.
arm group label: BCH Cohort
other name: Natus
intervention type: Procedure
intervention name: Bio-specimen Collection
description: Bio-specimen collection will include blood, urine, saliva, hair, stool, and a skin biopsy. Blood, urine, saliva, blood spots, and hair samples will also be banked for to-be-determined (TBD) studies.
arm group label: BCH Cohort
arm group label: Standard of Care Cohort
arm group label: iNTD Cohort
Bio-specimen collection will include blood, urine, saliva, hair, stool, and a skin biopsy.
      Blood, urine, saliva, blood spots, and hair samples will also be banked for to-be-determined
      (TBD) studies.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Phillip L Pearl, MD
role: Study Chair
affiliation: Boston Children's Hospital/Harvard Medical School
last name: K. Michael Gibson, PhD
role: Study Chair
affiliation: Washington State University
facility: 
facility: 
facility: 
facility: 
country: Germany
country: Spain
country: United Kingdom
country: United States
responsible party type: Principal Investigator
investigator affiliation: Boston Children's Hospital
investigator full name: Phillip Pearl
investigator title: Director of Epilepsy and Clinical Neurophysiology, William G. Lennox Chair, Boston Children's Hospital