Succinic Semialdehyde Dehydrogenase Deficiency Clinical Trial
Official title:
PET Imaging of GABA Receptors in Succinic Semialdehyde Dehydrogenase Deficiency
| Verified date | October 19, 2010 |
| Source | National Institutes of Health Clinical Center (CC) |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Observational |
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.
| Status | Completed |
| Enrollment | 42 |
| Est. completion date | October 19, 2010 |
| Est. primary completion date | |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 5 Years to 55 Years |
| Eligibility |
- INCLUSION CRITERIA: 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. - 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. EXCLUSION CRITERIA: - 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. |
| Country | Name | City | State |
|---|---|---|---|
| United States | National Institute of Neurological Disorders and Stroke (NINDS), 9000 Rockville | Bethesda | Maryland |
| United States | Childrens National Medical Center | Washington, D.C. | District of Columbia |
| Lead Sponsor | Collaborator |
|---|---|
| National Institute of Neurological Disorders and Stroke (NINDS) |
United States,
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. — View Citation
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. — View Citation
Arnold S, Berthele A, Drzezga A, Tölle 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. — View Citation
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Active, not recruiting |
NCT03758521 -
Natural History Study of Patients With Succinic Semialdehyde Dehydrogenase (SSADH) Deficiency
|