Trial record 3 of 4 for:    "Succinic semialdehyde dehydrogenase deficiency"

Phase 2 Clinical Trial of SGS-742 Therapy in Succinic Semialdehyde Dehydrogenase Deficiency

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )
ClinicalTrials.gov Identifier:
NCT02019667
First received: December 20, 2013
Last updated: March 21, 2014
Last verified: October 2013
  Purpose

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. SGS-742 is a GABA (B) receptor antagonist that has shown to be safe and well-tolerated in clinical trials in adults with cognitive impairment. In addition, preliminary data in the SSADH knockout mouse model suggest efficacy in this specific syndrome. The primary outcome measure will be a change in the Auditory Comprehension subtest of the Neuropsychological Assessment Battery Language Module score; the secondary outcome measure will be a change in cortical excitation and inhibition measured by transcranial magnetic stimulation (TMS). Additional evaluations will include neurological and neuropsychological examinations, magnetic resonance spectroscopy and CSF collection to measure GABA levels. The trial will have a baseline phase in which each patient will undergo a neurological examination and a neuropsychological evaluation. During the subsequent treatment phase, patients will be randomized to SGS-742, supplied by IRIX Pharmaceuticals, 600 mg t.i.d. given orally, or placebo, each for 6 months. Patients will then have repeat TMS, neurological and neuropsychological evaluations, followed by cross-over to the alternate treatment arm, and re-evaluation after 6 months.

Outcome Measures: The primary outcome measures for drug efficacy will be TMS parameters of cortical excitation and inhibition. The secondary outcome measure will be performance on neuropsychological testing. The outcome measures for safety will include clinical examination and neuropsychological tests.


Condition Intervention Phase
Metabolic Disease
Seizures
Drug: SGS-742
Drug: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Phase 2 Clinical Trial of SGS-742 Therapy in Succinic Semialdehyde Dehydrogenase Deficiency

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Auditory comprehension subtest of the Neuropsychological Assessment Battery Language Module [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 22
Study Start Date: December 2013
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Active drug
administration of SGS-742
Drug: SGS-742
N/A
Placebo Comparator: placebo
administration of placebo
Drug: Placebo
N/A

Detailed Description:

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. SGS-742 is a GABA (B) receptor antagonist that has shown to be safe and well-tolerated in clinical trials in adults with cognitive impairment. In addition, preliminary data in the SSADH knockout mouse model suggest efficacy in this specific syndrome. The primary outcome measure will be a change in the Auditory Comprehension subtest of the Neuropsychological Assessment Battery Language Module score; the secondary outcome measure will be a change in cortical excitation and inhibition measured by transcranial magnetic stimulation (TMS). Additional evaluations will include neurological and neuropsychological examinations, magnetic resonance spectroscopy and CSF collection to measure GABA levels. The trial will have a baseline phase in which each patient will undergo a neurological examination and a neuropsychological evaluation. During the subsequent treatment phase, patients will be randomized to SGS-742, supplied by IRIX Pharmaceuticals, 600 mg t.i.d. given orally, or placebo, each for 6 months. Patients will then have repeat TMS, neurological and neuropsychological evaluations, followed by cross-over to the alternate treatment arm, and re-evaluation after 6 months.

Outcome Measures: The primary outcome measures for drug efficacy will be TMS parameters of cortical excitation and inhibition. The secondary outcome measure will be performance on neuropsychological testing. The outcome measures for safety will include clinical examination and neuropsychological tests.

  Eligibility

Ages Eligible for Study:   8 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA
  • Aged 8 years or older
  • 4-hydroxybutyric aciduria (gamma-hydroxybutyric aciduria) on two separate tests
  • Documented succinic semialdehyde dehydrogenase enzyme deficiency
  • Patients must have clinical features consistent with SSADH deficiency including developmental delay especially deficit in expressive language, hypotonia, ataxia, seizures, and other neuropsychiatric symptoms including sleep disturbances, attention deficit, anxiety, obsessivecompulsive disorder, and autistic traits
  • Female patients of child bearing potential will have a pregnancy test prior to the study to ensure that pregnant patients will not participate in the study. During the study, women of child-bearing potential must use a reliable method of birth control until one month after the final drug taper is complete

EXCLUSION CRITERIA

  • Current alcohol use (> 14 drinks/wk in men and > 7 drinks/wk in women or or recreational drug use
  • Contraindications to MRI: metal in the body including pacemakers, medication pumps, aneurysm clips, metallic prostheses (including metal pins and rods, heart valves or cochlear implants), shrapnel fragments, permanent eye liner or small metal fragments in the eye that welders and other metal workers may have
  • Claustrophobia
  • Cannot lie comfortably flat on the back for up to 2h in the MRI scanner
  • Patients with a history of other major medical disorders with clinical fluctuations, or requiring therapy that might affect study participation or drug response such as severe depression or psychoses, renal or hepatic disease.
  • Patients requiring treatment with drugs known to affect the GABAergic system, including vigabatrin and benzodiazepines
  • Women who are pregnant or breast-feeding
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02019667

Contacts
Contact: Patricia M Reeves-Tyer, R. EEG T. (301) 496-1923 tyerp@ninds.nih.gov
Contact: William H Theodore, M.D. (301) 496-1505 theodorw@ninds.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
United States, Washington
Washington State University Recruiting
Pullman, Washington, United States
Sponsors and Collaborators
Investigators
Principal Investigator: William H Theodore, M.D. National Institute of Neurological Disorders and Stroke (NINDS)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )
ClinicalTrials.gov Identifier: NCT02019667     History of Changes
Other Study ID Numbers: 140033, 14-N-0033
Study First Received: December 20, 2013
Last Updated: March 21, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
GABA
Seizures
Neurotransmitters

Additional relevant MeSH terms:
Metabolic Diseases
Seizures
Amino Acid Metabolism, Inborn Errors
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Metabolism, Inborn Errors
Genetic Diseases, Inborn
(3-aminopropyl)(n-butyl)phosphinic acid
Neuroprotective Agents
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
GABA Antagonists
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 23, 2014