We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov Menu
Trial record 1 of 4 for:    "Succinic semialdehyde dehydrogenase deficiency"
Previous Study | Return to List | Next Study

PET Imaging of GABA Receptors in Succinic Semialdehyde Dehydrogenase Deficiency

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00246870
Recruitment Status : Completed
First Posted : October 31, 2005
Last Update Posted : July 2, 2017
Information provided by:

Study Description
Brief 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, 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.

Condition or disease
Succinic Semialdehyde Dehydrogenase Deficiency SSADH Deficiency

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

Study Type : Observational
Actual Enrollment : 42 participants
Official Title: PET Imaging of GABA Receptors in Succinic Semialdehyde Dehydrogenase Deficiency
Study Start Date : October 24, 2005
Estimated Study Completion Date : October 19, 2010

Groups and Cohorts

Outcome Measures

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   5 Years to 55 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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 of affected patients are, by definition, heterozygous carriers of mutations in the succinic semialdehyde dehydrogenase gene.


  • 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.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00246870

United States, District of Columbia
Childrens National Medical Center
Washington, D.C., District of Columbia, United States
United States, Maryland
National Institute of Neurological Disorders and Stroke (NINDS), 9000 Rockville
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
More Information

ClinicalTrials.gov Identifier: NCT00246870     History of Changes
Other Study ID Numbers: 060022
First Posted: October 31, 2005    Key Record Dates
Last Update Posted: July 2, 2017
Last Verified: October 19, 2010

Keywords provided by National Institutes of Health Clinical Center (CC):
Benzodiazepine Receptors
Succinic Semialdehyde Dehydrogenase
SSADH Deficiency
Healthy Volunteer

Additional relevant MeSH terms:
Amino Acid Metabolism, Inborn Errors
Developmental Disabilities
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Neurodevelopmental Disorders
Mental Disorders