Natural History Study of Patients With Succinic Semialdehyde Dehydrogenase (SSADH) Deficiency
| Status: | Recruiting |
|---|---|
| Conditions: | Cognitive Studies, Other Indications |
| Therapuetic Areas: | Psychiatry / Psychology, Other |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 2/17/2019 |
| Start Date: | January 15, 2019 |
| End Date: | December 2024 |
| Contact: | Melissa L DiBacco, MD |
| Email: | melissa.dibacco@childrens.harvard.edu |
| Phone: | 617-919-4617 |
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.
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.
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.
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.
We found this trial at
2
sites
300 Longwood Ave
Boston, Massachusetts 02115
Boston, Massachusetts 02115
(617) 355-6000
Principal Investigator: Phillip L Pearl, MD
Phone: 617-919-4617
Boston Children's Hospital Boston Children's Hospital is a 395-bed comprehensive center for pediatric health care....
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