Taurine Therapy for SSADH Deficiency

December 14, 2019 updated by: National Institute of Neurological Disorders and Stroke (NINDS)

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.

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.

Study Overview

Status

Completed

Conditions

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 Type

Observational

Enrollment (Actual)

7

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
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institutes of Health Clinical Center, 9000 Rockville Pike

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

10 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

  • INCLUSION CRITERIA:

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.

EXCLUSION CRITERIA:

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.

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?

Design Details

  • Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
TMS parameters of cortical excitation and inhibition.

Secondary Outcome Measures

Outcome Measure
Change in CSF GABA, GHB, succinic semialdehyde, homocarnosine, 4,5-dihydroxyhexanoic acid, D-2-hydroxyglutaric acid, homovanillic acid, and 5-HIAA levels.

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

April 27, 2012

Study Completion

December 16, 2013

Study Registration Dates

First Submitted

May 25, 2012

First Submitted That Met QC Criteria

May 25, 2012

First Posted (Estimate)

May 30, 2012

Study Record Updates

Last Update Posted (Actual)

December 17, 2019

Last Update Submitted That Met QC Criteria

December 14, 2019

Last Verified

December 16, 2013

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • 120123
  • 12-N-0123

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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