Succinic Semialdehyde DehydrogenaseNCT01608178
Taurine Therapy for SSADH Deficiency
An observational study of Succinic Semialdehyde Dehydrogenase, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
Background: Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare genetic disease that results in changes to certain brain chemicals. These chemicals may affect brain excitability, or how likely nerve cells are to turn on. Read more about this study
- Who is it for?
- Ages 12 years and olderHealthy volunteers can take part
- Conditions the study is for
- Succinic Semialdehyde Dehydrogenase
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Apr 2012to 16 Dec 2013
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Persistent 4-hydroxybutyric aciduria (gamma-hydroxybutyric aciduria).
- Documented succinic semialdehyde dehydrogenase enzyme deficiency.
- Patients will be at least 12 years old.
- Be enrolled in the taurine study at CNMC.
Who cannot join
- Pregnancy or lactation.
- Patients with a history of other significant medical disorders.
- Patients requiring treatment with drugs known to affect the GABAergic system, including vigabatrin, barbiturates, and benzodiazepines.
- Hearing loss. The effect of TMS on hearing is not fully known. Patients will be screened with an Audiometer.
- Abnormal platelets or coagulation studies suggesting increased risk for lumbar puncture or TMS
- Exclusions for MRI and MRS: pacemakers or other implanted electrical devices, brain stimulators, some types of dental implants, aneurysm clips (metal clips on the wall of a large artery), metallic prostheses (including metal pins and rods, heart valves, and cochlear implants), permanent eyeliner, implanted delivery pump, or shrapnel fragments, welders and metal workers.
- Exclusions for TMS: people with implanted medical devices such as pacemakers, implanted pumps, stimulators, or cochlear implants or in people who have metal objects inside the eye or skull.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Succinic Semialdehyde Dehydrogenase Deficiency: Physiological Markers of Taurine Therapy
Background:
- Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare genetic disease that results in changes to certain brain chemicals. These chemicals may affect brain excitability, or how likely nerve cells are to turn on. Changes in brain excitability may help to explain the symptoms of the disease, including learning and memory problems, seizures, and poor balance. A supplement called taurine may help people with SSADH deficiency by working on the brain chemical GABA. GABA helps to regulate brain activity. Researchers want to see if taurine can help people with SSADH deficiency.
Read more
Objectives:
- To learn more about how taurine affects the brain in people with SSADH deficiency.
Eligibility:
- Individuals at least 12 years of age who have SSADH deficiency.
Design:
- Participants will be screened with a physical exam and medical history. They will provide blood and urine samples. They will also take taurine supplements as part of this protocol.
- Participants will have two sets of study tests. One set will be given while participants are taking taurine. The second will be given when they are not taking it. Each testing session will take about 2 days to complete.
- Half of the participants will have the "off taurine" testing before starting on the taurine supplement. The other half will start taking taurine first, have the "on taurine" testing, and have the "off taurine" testing about 3 months after stopping taurine. Participants may decide the order in which they will have the testing done.
- Participants will have the following tests at the two test visits:
- Paper and pencil tests of learning and memory.
- Transcranial magnetic stimulation to study the excitability of nerve cells.
- Imaging studies to show GABA receptors in the brain and measure their activity.
- Electroencephalogram to measure brain waves.
- Lumbar puncture to collect spinal fluid.
- Participants will be monitored with regular study visits while they receive the taurine supplement treatment.
Read the detailed description
Objective: To study the physiologic effects of taurine therapy in patients with succinic semialdehyde Dehydrogenase (SSADH) deficiency.
Study Population: Eighteen children and adults with SSADH deficiency receiving taurine.
Design: This small open label trial will evaluate the effect of taurine treatment on key SSADH biomarkers and neurocognitive performance. Study evaluations will include neurological and neuropsychological examinations, positron emission tomography (PET) with 11C-flumazenil (FMZ), (optional and only for those over age 18), magnetic resonance spectroscopy (MRS) (optional) and cerebrospinal fluid (CSF) collection (optional) to measure gamma-aminobutyric acid (GABA) levels, and transcranial magnetic stimulation (TMS) to measure cortical excitation and inhibition, in patients given taurine for SSADH deficiency.
The evaluations will be performed twice, on and off therapy.
- Conditions
- Succinic Semialdehyde Dehydrogenase
- Keywords
- Pediatric Neurotransmitter Disorders, Succinic Semialdehyde Dehydrogenase, GABA, Epilepsy
- Medical subject headings
- Epilepsy
What is being measured
The primary outcome is the main question the study is designed to answer.
TMS parameters of cortical excitation and inhibition.
Secondary outcomes (1)
Change in CSF GABA, GHB, succinic semialdehyde, homocarnosine, 4,5-dihydroxyhexanoic acid, D-2-hydroxyglutaric acid, homovanillic acid, and 5-HIAA levels.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2012 (estimated)
- Study start27 Apr 2012
- Study completion16 Dec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Succinic Semialdehyde DehydrogenaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Time perspective
- Prospective
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)
- Sponsor type
- US National Institutes of Health
- Investigators
- William H Theodore, M.D., Principal investigator, National Institute of Neurological Disorders and Stroke (NINDS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01608178
- Sponsor's protocol ID
- 120123
- Other IDs
- 12-N-0123
- Status last verified
- 16 Dec 2013
- First submitted
- 25 May 2012
- Last updated
- 17 Dec 2019
- Results posted
- No
Publications
Al-Essa MA, Bakheet SM, Patay ZJ, Powe JE, Ozand PT. Clinical, fluorine-18 labeled 2-fluoro-2-deoxyglucose positron emission tomography (FDG PET), MRI of the brain and biochemical observations in a patient with 4-hydroxybutyric aciduria; a progressive neurometabolic disease. Brain Dev. 2000 Mar;22(2):127-31. doi: 10.1016/s0387-7604(99)00121-7.
PubMed 10722966Arnulf I, Konofal E, Gibson KM, Rabier D, Beauvais P, Derenne JP, Philippe A. Effect of genetically caused excess of brain gamma-hydroxybutyric acid and GABA on sleep. Sleep. 2005 Apr;28(4):418-24. doi: 10.1093/sleep/28.4.418.
PubMed 16171286Simmons FB. Letter: Stellate ganglion blocks for idiopathic sensorineural hearing loss. Arch Otolaryngol. 1976 Jun;102(6):384-5. doi: 10.1001/archotol.1976.00780110096021. No abstract available.
PubMed 1275811
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Succinic Semialdehyde Dehydrogenase Deficiency: Physiological Markers of Taurine Therapy
- ClinicalTrials.gov ID
- NCT01608178
- Acronym / sponsor ID
- 120123
- Conditions
- Succinic Semialdehyde Dehydrogenase
- Keywords
- Pediatric Neurotransmitter Disorders, Succinic Semialdehyde Dehydrogenase, GABA, Epilepsy
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 27 Apr 2012
- Study completion
- 16 Dec 2013
- First posted
- 30 May 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare genetic disease that results in changes to certain brain chemicals. These chemicals may affect brain excitability, or how likely nerve cells are to turn on. Changes in brain excitability may help to explain the symptoms of the disease, including learning and memory problems, seizures, and poor balance. A supplement called taurine may help people with SSADH deficiency by working on the brain chemical GABA. GABA helps to regulate brain activity. Researchers want to see if taurine can help people with SSADH deficiency.
Objectives:
- To learn more about how taurine affects the brain in people with SSADH deficiency.
Eligibility:
- Individuals at least 12 years of age who have SSADH deficiency.
Design:
- Participants will be screened with a physical exam and medical history. They will provide blood and urine samples. They will also take taurine supplements as part of this protocol.
- Participants will have two sets of study tests. One set will be given while participants are taking taurine. The second will be given when they are not taking it. Each testing session will take about 2 days to complete.
- Half of the participants will have the "off taurine" testing before starting on the taurine supplement. The other half will start taking taurine first, have the "on taurine" testing, and have the "off taurine" testing about 3 months after stopping taurine. Participants may decide the order in which they will have the testing done.
- Participants will have the following tests at the two test visits:
- Paper and pencil tests of learning and memory.
- Transcranial magnetic stimulation to study the excitability of nerve cells.
- Imaging studies to show GABA receptors in the brain and measure their activity.
- Electroencephalogram to measure brain waves.
- Lumbar puncture to collect spinal fluid.
- Participants will be monitored with regular study visits while they receive the taurine supplement treatment.
Detailed description
Objective: To study the physiologic effects of taurine therapy in patients with succinic semialdehyde Dehydrogenase (SSADH) deficiency.
Study Population: Eighteen children and adults with SSADH deficiency receiving taurine.
Design: This small open label trial will evaluate the effect of taurine treatment on key SSADH biomarkers and neurocognitive performance. Study evaluations will include neurological and neuropsychological examinations, positron emission tomography (PET) with 11C-flumazenil (FMZ), (optional and only for those over age 18), magnetic resonance spectroscopy (MRS) (optional) and cerebrospinal fluid (CSF) collection (optional) to measure gamma-aminobutyric acid (GABA) levels, and transcranial magnetic stimulation (TMS) to measure cortical excitation and inhibition, in patients given taurine for SSADH deficiency.
The evaluations will be performed twice, on and off therapy.
Study design
- Time perspective
- Prospective
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Persistent 4-hydroxybutyric aciduria (gamma-hydroxybutyric aciduria).
- Documented succinic semialdehyde dehydrogenase enzyme deficiency.
- Patients will be at least 12 years old.
- Be enrolled in the taurine study at CNMC.
Key exclusion criteria (7 listed)
- Pregnancy or lactation.
- Patients with a history of other significant medical disorders.
- Patients requiring treatment with drugs known to affect the GABAergic system, including vigabatrin, barbiturates, and benzodiazepines.
- Hearing loss. The effect of TMS on hearing is not fully known. Patients will be screened with an Audiometer.
- Abnormal platelets or coagulation studies suggesting increased risk for lumbar puncture or TMS
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
TMS parameters of cortical excitation and inhibition.
1 secondary outcome
Change in CSF GABA, GHB, succinic semialdehyde, homocarnosine, 4,5-dihydroxyhexanoic acid, D-2-hydroxyglutaric acid, homovanillic acid, and 5-HIAA levels.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2019.
- Background: PubMed 10722966Al-Essa MA, Bakheet SM, Patay ZJ, Powe JE, Ozand PT. Clinical, fluorine-18 labeled 2-fluoro-2-deoxyglucose positron emission tomography (FDG PET), MRI of the brain and biochemical observations in a patient with 4-hydroxybutyric aciduria; a progressive neurometabolic disease. Brain Dev. 2000 Mar;22(2):127-31. doi: 10.1016/s0387-7604(99)00121-7.
- Background: PubMed 16171286Arnulf I, Konofal E, Gibson KM, Rabier D, Beauvais P, Derenne JP, Philippe A. Effect of genetically caused excess of brain gamma-hydroxybutyric acid and GABA on sleep. Sleep. 2005 Apr;28(4):418-24. doi: 10.1093/sleep/28.4.418.
- Background: PubMed 1275811Simmons FB. Letter: Stellate ganglion blocks for idiopathic sensorineural hearing loss. Arch Otolaryngol. 1976 Jun;102(6):384-5. doi: 10.1001/archotol.1976.00780110096021. No abstract available.
Related trials for Succinic Semialdehyde Dehydrogenase
RecruitingObservational study
Natural History Study of Patients With Succinic Semialdehyde Dehydrogenase (SSADH) Deficiency
Succinic Semialdehyde Dehydrogenase Deficiency
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
William H Theodore, M.D. principal investigator
National Institute of Neurological Disorders and Stroke (NINDS)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Succinic Semialdehyde Dehydrogenase, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
TMS parameters of cortical excitation and inhibition.. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01608178, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2019; AzTrials last refreshed its copy on 29 Oct 2026.