PET Imaging of GABA Receptors in Succinic Semialdehyde Dehydrogenase Deficiency

June 30, 2017 updated by: National Institute of Neurological Disorders and Stroke (NINDS)

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.

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Study Overview

Status

Completed

Conditions

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 Type

Observational

Enrollment (Actual)

42

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

5 years to 55 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Neurological Disorders and Stroke (NINDS)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 24, 2005

Study Completion

October 19, 2010

Study Registration Dates

First Submitted

October 29, 2005

First Submitted That Met QC Criteria

October 29, 2005

First Posted (Estimate)

October 30, 2005

Study Record Updates

Last Update Posted (Actual)

July 2, 2017

Last Update Submitted That Met QC Criteria

June 30, 2017

Last Verified

October 19, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 060022
  • 06-N-0022

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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