Arginine and Buphenyl in Patients With Argininosuccinic Aciduria (ASA), a Urea Cycle Disorder
Condition: Argininosuccinic Aciduria; Amino Acid Metabolism, Inborn Errors; Urea Cycle Disorders
MeSH terms: Urea Cycle Disorders, Inborn; Argininosuccinic Aciduria; Metabolism, Inborn Errors; Amino Acid Metabolism, Inborn Errors
Intervention: Sodium Phenylbutyrate; Arginine
Intervention description: None will be administered during the washout period; 500 mg/kg/day or 10 grams/m2 will be administered during the first one week treatment period in addition to arginine; Standard therapeutic dose of 500 mg/kg/day or 10 grams/2 will be administered during the washout periods, during the first one week treatment period when receiving arginine plus Buphenyl, 100 mg/kg/day or 2 grams/m2 will be administered, during the second treatment week, when receiving arginine alone, 500 mg/kg/day or 10 grams/m2 will be administered
Intervention MeSH terms: 4-phenylbutyric acid
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 12.0
Sex: All
Minimum age: 5 Years
Healthy volunteers: No
Keywords: Argininosuccinic Acid Lyase Deficiency; ASA

Summary:

      Urea cycle disorders are inherited illnesses in which the body does not produce enough of the
      chemicals that remove ammonia, a byproduct of protein metabolism, from the blood stream.
      Elevated ammonia levels can lead to brain damage and death. Argininosuccinic aciduria (ASA)
      is a type of urea cycle disorder that is characterized specifically by high levels of
      argininosuccinic acid, a chemical involved in the urea cycle. People with ASA are at risk for
      serious liver damage, which may be due to the elevated levels of argininosuccinic acid.
      Sodium phenylbutyrate (Buphenyl-TM) is a drug that has been used to treat other types of urea
      cycle disorders. This study will evaluate whether Buphenyl-TM in conjunction with decreased
      arginine dose (in addition to a normal regimen of protein) will improve short-term liver
      function and decrease plasma citrulline and ASA levels in people with ASA.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Has confirmed diagnosis of ASA by amino acid or enzyme assay

          -  Has a history of adequate compliance to the diet and treatment

          -  Able to take oral or G-tube medication

          -  Able to perform 24 hour urine collection

          -  Agrees to travel to Baylor College of Medicine

          -  If female, of child bearing potential, and sexually active, agrees to use an
             acceptable method of birth control

          -  Greater than 5 years of age

        Exclusion Criteria:

          -  Has a history of congestive heart failure, severe renal insufficiency, or any
             condition that causes sodium retention or edema

          -  Currently taking Probenecid, Haloperidol, Valproate or oral corticosteroids

          -  Pregnant or lactating

          -  Currently being treated for an acute illness

          -  Has co-morbid associations causing difficulties in the detection of hyperammonemic
             episodes, liver damage, or difficulties in the diet compliance

          -  Has known hypersensitivity to sodium phenylbutyrate

          -  Has taken any experimental medication within the last 30 days

          -  Has renal insufficiency with creatinine greater than 1.5 mg/dl at screening