What this study is
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.
What's being tested
- Transcranial magnetic stimulation (TMS)
Intervention · DEVICE
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)
Intervention · DEVICE
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)
Intervention · DEVICE
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
Intervention · PROCEDURE
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 details
- Sponsor
- Boston Children's Hospital
- Conditions
- Succinic Semialdehyde Dehydrogenase Deficiency
- Enrolling
- 55 people
- Starts
- 2019-01-15
- Est. completion
- 2029-06
- Record
- View on ClinicalTrials.gov ↗
Who can join
Sex ALLHealthy volunteers Not acceptedYou may qualify if
- 4-hydroxybutyric aciduria (γ-hydroxybutyric aciduria)
- Documented pathogenic ALDH5A1 (aldehyde dehydrogenase 5A1 gene) mutation
- 0-99 years
You can't join if
- Active or recent substance abuse or dependence within the past year.
- 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.
Sign in and we'll check these against your records.Full criteria on ClinicalTrials.gov ↗
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Study locations (4)
3 openBoston Children's Hospital
Boston, Massachusetts, United States
- Melissa L DiBacco, MD · Contact6179194617melissa.dibacco@childrens.harvard.edu
- Phillip L Pearl, MD · Principal investigator
Recruiting
3 sites outside the US
University Children's Hospital
Heidelberg, Heidelberg, Germany
- Kathrin Jeltsch, MD · ContactKathrin.Jeltsch@med.uni-heidelberg.de
- Thomas Opladen, MD · Principal investigator
RecruitingBirmingham Children's Hospital NHS Foundation Trust
Birmingham, United Kingdom
- Allie Berry · Contactalison.berry1@nhs.net
- Evangeline Wassmer · Principal investigator
Not yet recruitingSant Joan de Deu Hospital Barcelona
Barcelona, Spain
Active, not recruiting
Study team
Sponsor
Boston Children's Hospital
Study ID IRB-P00029917
Study chair
Phillip L Pearl, MD
Boston Children's Hospital/Harvard Medical School
Study chair
K. Michael Gibson, PhD
Washington State University
Frequently asked questions
The sponsor hasn't published answers to common questions for this trial.