5 Clinical Trials for Various Conditions
Succinic Semialdehyde Dehydrogenase deficiency (SSADHD) is a rare autosomal recessive disease that interferes with the catabolism of the major inhibitory neurotransmitter gamma-amino butyric acid (GABA) and furthermore leads to accumulation of various potential toxic metabolites, most prominently gamma hydroxybutyric acid (GHB). Current research indicates that there is developmental delay and significant neurophysiological and biochemical alterations in SSADHD patients, but whether disease presentation varies with age is not known. The investigators propose to determine the natural course of the clinical presentation of SSADHD; to determine the natural course of neurophysiological and biochemical indices known to be altered in SSADHD; and to identify neurophysiological and biochemical predictors of clinical severity. The overall objective is to define the natural course of the clinical, neurophysiological and biochemical spectrum of SSADHD. Secondary objectives include the identification of biomarkers that correlate with disease phenotype and predict clinical outcomes, and the creation of an international SSADHD data repository for future investigation of pathogenesis and therapy.
Objective: To perform a clinical trial assessing the safety, tolerability and efficacy of the GABA(B) receptor antagonist SGS-742 in patients with SSADH deficiency. Study Population: Twenty-two children and adults with SSADH deficiency. Design: Double-blind, cross-over, phase II clinical trial. Outcome Measures: The primary outcome measures for drug efficacy will be performance on neuropsychological testing and responses to parent questionnaire. The secondary outcome measure will be TMS parameters of cortical excitation and inhibition. The outcome measures for safety will include clinical examination and neuropsychological tests.
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. ...
This study will measure brain excitability in patients with succinic semialdehyde dehydrogenase (SSADH) deficiency, and in their parents. SSADH is a rare inherited disease in which changes in certain brain chemicals affect brain cell activity. Symptoms vary greatly among patients, and may include mental retardation, impaired ability to coordinate movements, and delays in language and speech development. Other symptoms may include poor muscle tone, uncontrolled seizures and other neurological or behavioral abnormalities. Test findings in patients and their parents will be compared with those of healthy normal volunteers. The following individuals may be eligible for this study: patients with SSADH who are between 5 and 24 years of age; parents of patients who are between 18 and 55 years of age; healthy normal children who are between 10 and 17 years of age; and healthy normal adults who are between 18 and 55 years of age. Candidates are screened with blood and urine tests. All participants undergo the following: * Transcranial magnetic stimulation (TMS): This procedure maps brain function. A wire coil is held on the scalp, and a brief electrical current is passed through the coil, creating a magnetic pulse that stimulates the brain. During the stimulation, the subject may be asked to tense certain muscles slightly or perform other simple actions to help position the coil properly. The stimulation may cause a twitch in muscles of the face, arm, or leg, and the subject may hear a click and feel a pulling sensation on the skin under the coil. During the test, electrical activity of muscles is recorded with a computer or other recording device, using electrodes attached to the skin with tape. * Magnetic resonance imaging (MRI): This test combines a powerful magnet with an advanced computer system and radio waves to produce accurate, detailed pictures of organs and tissues. During the scan, the subject lies on a table in a narrow cylinder containing a magnetic field, wearing ear plugs to muffle loud noises that occur with electrical switching of the magnetic fields. He or she can speak with a staff member via an intercom system at all times during the procedure. In addition to standard MRI, subjects may have newer MRI tests, such as diffusion tensor MRI and magnetic resonance spectroscopy. In addition to the above, patients and their parents may also undergo the following tests: * Electroencephalography (EEG): This test records brain waves (electrical activity of the brain). Electrodes are placed on the scalp and brain electrical activity is recorded while the subject lies quietly, breathes deeply, watches flashes of light, or sleeps. Some patients may also have video-EEG monitoring, which involves simultaneous clinical recording using a video camera along with brain wave recording. * Sleep study and multiple sleep latency onset testing (MSLT): Electrodes are placed on the subject's scalp and remain there while the subject sleeps in the hospital overnight. MSLT is done the next day, starting 2 hours after the subject wakes up from the night's sleep. A total of five 20- to 30-minute naps are recorded, each every 2 hours, to access daytime sleepiness. * Nerve conduction studies: This test measures the speed with which nerves conduct electrical impulses and the strength of the connection between the nerve and the muscle. A probe is placed on the skin to deliver a small electrical stimulus, and wires taped on the skin record the impulses.
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.