Succinic Semialdehyde Dehydrogenase DeficiencyNCT00246870
PET Imaging of GABA Receptors in Succinic Semialdehyde Dehydrogenase Deficiency
An observational study of Succinic Semialdehyde Dehydrogenase Deficiency and SSADH Deficiency, run by National Institute of Neurological Disorders and Stroke (NINDS) at 2 sites in United States.
Trial summary
This study will use brain imaging to map brain cell receptors for a chemical called GABA, a chemical that inhibits the activities of nerve cells. The study includes patients with succinic semialdehyde dehydrogenase deficiency, or SSADH (a disorder in which an enzyme deficiency disrupts GABA metabolism), their parents… Read more about this study
- Who is it for?
- Ages 5 to 55 years
- Conditions the study is for
- Succinic Semialdehyde Dehydrogenase Deficiency, SSADH Deficiency
- How many people
- 42 participants
- Where
- 2 sitesUnited States
- Study dates
- 24 Oct 2005to 19 Oct 2010
- 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 5 to 55 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients
- Clinical characteristics consistent with SSADH deficiency.
- Persistent 4-hydroxybutyric aciduria (gamma-hydroxybutyric aciduria)
- Documented leucocyte extract succinic semialdehyde dehydrogenase enzyme deficiency
- English-speaking (or the ability to understand English as a second language)
- Patients may be male or female.
Show all 10Show fewer
- Female patients of child bearing potential will have a pregnancy test within 24 hours of the study to ensure that pregnant patients will not participate.
- During the study, woman of child bearing potential must use a reliable method of birth control.
- Parents
- -Parents of affected patients are, by definition, heterozygous carriers of mutations in the succinic semialdehyde dehydrogenase gene.
Who cannot join
- Neither patients nor healthy volunteers may suffer from mental or physical illness that would interfere with participation.
- Neither patients nor healthy volunteers may be pregnant or nursing
- Neither patients nor healthy volunteers may use alcohol or recreational drugs during the study
- Patients requiring treatment of drugs known to affect the GABAergic system, including vigabatrin.
- Patients who had seizure activity 24 hours prior to the study.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
National Institute of Neurological Disorders and Stroke (NINDS), 9000 Rockville
Bethesda, Maryland, 20892
Childrens National Medical Center
Washington D.C., District of Columbia
About this study
This study will use brain imaging to map brain cell receptors for a chemical called GABA, a chemical that inhibits the activities of nerve cells. The study includes patients with succinic semialdehyde dehydrogenase deficiency, or SSADH (a disorder in which an enzyme deficiency disrupts GABA metabolism), their parents, and healthy volunteers. SSADH deficiency causes various neurological and neuromuscular problems, including mild to severe mental retardation, delays in the acquisition of skills requiring the coordination of mental and physical activities (psychomotor retardation), delays in language and speech development, and other symptoms.
Healthy volunteers 18-55 years of age, patients with SSADH between 5 and 24 years of age, and parents of patients 18-55 years of age may be eligible for this study.
Read more
Participants undergo magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning as follows:
Magnetic resonance imaging
MRI uses a magnetic field and radio waves to produce images of body tissues and organs. For this procedure, the subject lies on a table that is moved into the scanner (a narrow metal cylinder surrounded by a magnetic field) wearing earplugs to muffle loud knocking and thumping sounds that occur during the scanning process. Scanning time varies from 20 minutes to 3 hours, with most scans lasting between 45 and 90 minutes. Participants may be asked to lie still for up to 90 minutes at a time. In addition to standard MRI, participants may also have new types of MRI that may detect brain abnormalities when regular MRI is normal, such as diffusion tensor MRI and magnetic resonance spectroscopy. There are no noticeable differences from ordinary MRI scans.
Positron Emission Tomography
A catheter (plastic tube) is placed in a vein in the subject's wrist. The subject lies on a table with his or her head placed in the scanner. A mask, used to help keep the head still in the scanner, is placed over the head. The mask is not uncomfortable and has holes for the subject to see through. A radioactive compound called flumazenil is injected into a vein. The scan takes about 90 minutes.
Some children need to be sedated for PET or MRI scans. In these cases, chloral hydrate, a standard drug for pediatric diagnostic procedures, is used.
...
Read the detailed description
Objective: To measure CNS GABA receptors and GABA levels in patients with succinic semialdehyde dehydrogenase (SSADH) deficiency, a severe pediatric neurotransmitter disease.
Study Population: The study will include children and young adult patients with the disorder, as well as parents of patients (obligate heterozygotes), and adult normal volunteers.
Design: this is a natural history study using neuroimaging techniques. We will perform 11C-flumazenil PET scans, and magnetic resonance spectroscopy (MRS). We will perform neurological examinations to obtain data on clinical manifestations of the condition.
Outcome measures: The outcome measures will be the distribution of CNS binding of 11C-flumazenil, and brain GABA levels measured by MRS, and their relation to clinical manifestations such as motor, speech, and language impairment, hypotonia, hyporreflexia, and seizures. We expect to show that patients with SSADH deficiency will have multifocal reductions in FMZ binding and increased brain GABA levels in a similar pattern.
- Keywords
- Seizures, Development, Pediatric, Benzodiazepine Receptors, Neurotransmission, Succinic Semialdehyde Dehydrogenase, Deficiency, SSADH Deficiency, Healthy Volunteer, HV
- Medical subject headings
- succinic semialdehyde dehydrogenase deficiency, Seizures
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2005 (estimated)
- Study start24 Oct 2005
- Study completion19 Oct 2010
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 Dehydrogenase DeficiencyStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The sponsor's other registered studies.
- 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
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00246870
- Sponsor's protocol ID
- 060022
- Other IDs
- 06-N-0022
- Status last verified
- 19 Oct 2010
- First submitted
- 29 Oct 2005
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Akaboshi S, Hogema BM, Novelletto A, Malaspina P, Salomons GS, Maropoulos GD, Jakobs C, Grompe M, Gibson KM. Mutational spectrum of the succinate semialdehyde dehydrogenase (ALDH5A1) gene and functional analysis of 27 novel disease-causing mutations in patients with SSADH deficiency. Hum Mutat. 2003 Dec;22(6):442-50. doi: 10.1002/humu.10288.
PubMed 14635103Al-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 10722966Arnold S, Berthele A, Drzezga A, Tolle TR, Weis S, Werhahn KJ, Henkel A, Yousry TA, Winkler PA, Bartenstein P, Noachtar S. Reduction of benzodiazepine receptor binding is related to the seizure onset zone in extratemporal focal cortical dysplasia. Epilepsia. 2000 Jul;41(7):818-24. doi: 10.1111/j.1528-1157.2000.tb00248.x.
PubMed 10897152
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PET Imaging of GABA Receptors in Succinic Semialdehyde Dehydrogenase Deficiency
- ClinicalTrials.gov ID
- NCT00246870
- Acronym / sponsor ID
- 060022
- Keywords
- Seizures, Development, Pediatric, Benzodiazepine Receptors, Neurotransmission, Succinic Semialdehyde Dehydrogenase, Deficiency, SSADH Deficiency
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 24 Oct 2005
- Study completion
- 19 Oct 2010
- First posted
- 31 Oct 2005 (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.
This study will use brain imaging to map brain cell receptors for a chemical called GABA, a chemical that inhibits the activities of nerve cells. The study includes patients with succinic semialdehyde dehydrogenase deficiency, or SSADH (a disorder in which an enzyme deficiency disrupts GABA metabolism), their parents, and healthy volunteers. SSADH deficiency causes various neurological and neuromuscular problems, including mild to severe mental retardation, delays in the acquisition of skills requiring the coordination of mental and physical activities (psychomotor retardation), delays in language and speech development, and other symptoms.
Healthy volunteers 18-55 years of age, patients with SSADH between 5 and 24 years of age, and parents of patients 18-55 years of age may be eligible for this study.
Participants undergo magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning as follows:
Magnetic resonance imaging
MRI uses a magnetic field and radio waves to produce images of body tissues and organs. For this procedure, the subject lies on a table that is moved into the scanner (a narrow metal cylinder surrounded by a magnetic field) wearing earplugs to muffle loud knocking and thumping sounds that occur during the scanning process. Scanning time varies from 20 minutes to 3 hours, with most scans lasting between 45 and 90 minutes. Participants may be asked to lie still for up to 90 minutes at a time. In addition to standard MRI, participants may also have new types of MRI that may detect brain abnormalities when regular MRI is normal, such as diffusion tensor MRI and magnetic resonance spectroscopy. There are no noticeable differences from ordinary MRI scans.
Positron Emission Tomography
A catheter (plastic tube) is placed in a vein in the subject's wrist. The subject lies on a table with his or her head placed in the scanner. A mask, used to help keep the head still in the scanner, is placed over the head. The mask is not uncomfortable and has holes for the subject to see through. A radioactive compound called flumazenil is injected into a vein. The scan takes about 90 minutes.
Some children need to be sedated for PET or MRI scans. In these cases, chloral hydrate, a standard drug for pediatric diagnostic procedures, is used.
...
Detailed description
Objective: To measure CNS GABA receptors and GABA levels in patients with succinic semialdehyde dehydrogenase (SSADH) deficiency, a severe pediatric neurotransmitter disease.
Study Population: The study will include children and young adult patients with the disorder, as well as parents of patients (obligate heterozygotes), and adult normal volunteers.
Design: this is a natural history study using neuroimaging techniques. We will perform 11C-flumazenil PET scans, and magnetic resonance spectroscopy (MRS). We will perform neurological examinations to obtain data on clinical manifestations of the condition.
Outcome measures: The outcome measures will be the distribution of CNS binding of 11C-flumazenil, and brain GABA levels measured by MRS, and their relation to clinical manifestations such as motor, speech, and language impairment, hypotonia, hyporreflexia, and seizures. We expect to show that patients with SSADH deficiency will have multifocal reductions in FMZ binding and increased brain GABA levels in a similar pattern.
Study design
Who may qualify
- Ages
- 5 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (10 listed)
- Patients
- Clinical characteristics consistent with SSADH deficiency.
- Persistent 4-hydroxybutyric aciduria (gamma-hydroxybutyric aciduria)
- Documented leucocyte extract succinic semialdehyde dehydrogenase enzyme deficiency
- English-speaking (or the ability to understand English as a second language)
Key exclusion criteria (5 listed)
- Neither patients nor healthy volunteers may suffer from mental or physical illness that would interfere with participation.
- Neither patients nor healthy volunteers may be pregnant or nursing
- Neither patients nor healthy volunteers may use alcohol or recreational drugs during the study
- Patients requiring treatment of drugs known to affect the GABAergic system, including vigabatrin.
- Patients who had seizure activity 24 hours prior to the study.
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
Not reported in the source record.
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 2 Jul 2017.
- Background: PubMed 14635103Akaboshi S, Hogema BM, Novelletto A, Malaspina P, Salomons GS, Maropoulos GD, Jakobs C, Grompe M, Gibson KM. Mutational spectrum of the succinate semialdehyde dehydrogenase (ALDH5A1) gene and functional analysis of 27 novel disease-causing mutations in patients with SSADH deficiency. Hum Mutat. 2003 Dec;22(6):442-50. doi: 10.1002/humu.10288.
- 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 10897152Arnold S, Berthele A, Drzezga A, Tolle TR, Weis S, Werhahn KJ, Henkel A, Yousry TA, Winkler PA, Bartenstein P, Noachtar S. Reduction of benzodiazepine receptor binding is related to the seizure onset zone in extratemporal focal cortical dysplasia. Epilepsia. 2000 Jul;41(7):818-24. doi: 10.1111/j.1528-1157.2000.tb00248.x.
Related trials for Succinic Semialdehyde Dehydrogenase Deficiency
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.
The record lists no contact. Use the official record to reach the sponsor.
2 sites 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 Deficiency and SSADH Deficiency, run by National Institute of Neurological Disorders and Stroke (NINDS) at 2 sites 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 10 inclusion and 5 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 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00246870, 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 2 Jul 2017.