Recruiting

Observational Study

Sponsor:

Boston Children's Hospital

Code:

NCT03758521

Conditions

Succinic Semialdehyde Dehydrogenase Deficiency

Eligibility Criteria

Sex: All

Age: 0+

Healthy Volunteers: Not accepted

Interventions

Transcranial magnetic stimulation (TMS)

Magnetic resonance imaging (MRI)

Electroencephalogram (EEG)

Bio-specimen Collection

Study Details

Brief summary:

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.

Conditions

Succinic Semialdehyde Dehydrogenase Deficiency

Study ID

NCT03758521

Start date

Jan 15, 2019

Status verified date

Jan, 2026

Completion date

Jun, 2029

Anticipated

Primary completion date

May 31, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 0+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 4-hydroxybutyric aciduria (γ-hydroxybutyric aciduria)
  • documented pathogenic ALDH5A1 (aldehyde dehydrogenase 5A1 gene) mutation
  • 0-99 years

Exclusion Criteria:

  • 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.

Study Design

Enrollment

55 participants

Anticipated

Interventions and Outcome Measures

Arms

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.

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.

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.

Interventions

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.

Primary outcome measure

  • Clinical Severity Score [ Time Frame: 5 Years ]
  • Biochemical - GABA measurement [ Time Frame: 5 Years ]
  • Biochemical - GHB measurement [ Time Frame: 5 Years ]
  • Quantification of GABA related signals on the MRI spectroscopy [ Time Frame: 5 Years ]

Central Contacts and Locations

Central contacts

Melissa L DiBacco, MD

617-919-4617melissa.dibacco@childrens.harvard.edu

Locations

Boston Children's Hospital

Recruiting

Boston, Massachusetts, United States, 02115

Contacts

Melissa L DiBacco, MD

6179194617melissa.dibacco@childrens.harvard.edu

Principal Investigator:

Phillip L Pearl, MD

More Information

Sponsor

Boston Children's Hospital

Last update posted

Jan 13, 2026

Last verified

Jan, 2026

Keywords

  • SSADHD
  • SSADH deficiency

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Boston Children's Hospital on 2026-01-13.