Phase 2 Clinical Trial of SGS-742 Therapy in Succinic Semialdehyde Dehydrogenase Deficiency
Condition: Metabolic Disease; Seizures
MeSH terms: Seizures; Metabolic Diseases
Intervention: SGS-742; Placebo
Intervention MeSH terms: (3-aminopropyl)(n-butyl)phosphinic acid
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 19.0
Sex: All
Minimum age: 4 Years
Healthy volunteers: No
Keywords: GABA; Seizures; Neurotransmitters

Summary:

      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.
    

Eligibility criteria:

        -  INCLUSION CRITERIA

          -  Aged 4 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

          -  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.

          -  Pregnant and lactating women