Natural History Study of Patients with Succinic Semialdehyde Dehydrogenase (SSADH) Deficiency
NCT ID: NCT03758521
Last Updated: 2024-12-16
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
55 participants
OBSERVATIONAL
2019-01-15
2029-06-30
Brief Summary
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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.
Detailed Description
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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.
Conditions
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Keywords
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Study Design
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COHORT
PROSPECTIVE
Study Groups
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BCH Cohort
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.
Transcranial magnetic stimulation (TMS)
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.
Magnetic resonance imaging (MRI)
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.
Electroencephalogram (EEG)
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.
Bio-specimen Collection
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.
iNTD Cohort
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.
Bio-specimen Collection
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.
Standard of Care Cohort
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.
Bio-specimen Collection
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.
Interventions
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Transcranial magnetic stimulation (TMS)
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.
Magnetic resonance imaging (MRI)
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.
Electroencephalogram (EEG)
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.
Bio-specimen Collection
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.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* documented pathogenic ALDH5A1 (aldehyde dehydrogenase 5A1 gene) mutation
* 0-99 years
Exclusion Criteria
* inability to participate in the study procedures.
* any condition that makes the study subject, in the opinion of the investigator, unsuitable for the study.
* patients will be excluded from the MRI section of the study if they have: implanted cardiac pacemaker or autodefibrillators, implanted neural pacemakers, cochlear implants, metallic foreign bodies in the eye or Central Nervous System (CNS), any implanted wire or metal device that may concentrate radio frequency fields.
* patients less than age two years will be excluded from the TMS procedure.
ALL
No
Sponsors
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Washington State University
OTHER
University of South Florida
OTHER
University Hospital Heidelberg
OTHER
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
NIH
Boston Children's Hospital
OTHER
Responsible Party
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Phillip Pearl
Director of Epilepsy and Clinical Neurophysiology, William G. Lennox Chair, Boston Children's Hospital
Principal Investigators
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Phillip L Pearl, MD
Role: STUDY_CHAIR
Boston Children's Hospital/Harvard Medical School
K. Michael Gibson, PhD
Role: STUDY_CHAIR
Washington State University
Locations
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Boston Children's Hospital
Boston, Massachusetts, United States
University Children's Hospital
Heidelberg, Heidelberg, Germany
Sant Joan de Deu Hospital Barcelona
Barcelona, , Spain
Birmingham Children's Hospital NHS Foundation Trust
Birmingham, , United Kingdom
Countries
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References
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Tokatly Latzer I, Lee HHC, Yang E, Alves C, Bertoldi M, Fung C, Steele SV, Kule E, Jin Z, Rotenberg A, Roullet JB, Pearl PL. Central Dysmyelination in SSADH-Deficient Humans and Mice. Ann Clin Transl Neurol. 2025 Jul 31. doi: 10.1002/acn3.70148. Online ahead of print.
Tokatly Latzer I, Roullet JB, Afshar-Saber W, Lee HHC, Bertoldi M, McGinty GE, DiBacco ML, Arning E, Tsuboyama M, Rotenberg A, Opladen T, Jeltsch K, Garcia-Cazorla A, Julia-Palacios N, Gibson KM, Sahin M, Pearl PL. Clinical and molecular outcomes from the 5-Year natural history study of SSADH Deficiency, a model metabolic neurodevelopmental disorder. J Neurodev Disord. 2024 Apr 24;16(1):21. doi: 10.1186/s11689-024-09538-9.
Other Identifiers
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IRB-P00029917
Identifier Type: -
Identifier Source: org_study_id