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Phase 2 N=12 Randomized Double-blind Treatment

Arginine and Buphenyl in Patients With Argininosuccinic Aciduria (ASA), a Urea Cycle Disorder

Argininosuccinic Aciduria · Amino Acid Metabolism, Inborn Errors · Urea Cycle Disorders

Enrolled (actual)
12
Serious AEs
0.0%
Results posted
Nov 2014
Primary outcome: Primary: Measures of Liver Function: AST and ALT — 36.2; 52; 31.7; 57.86 IU/L

Study Design & Population

Study type
Interventional
Phase
Phase 2
Interventions
Sodium Phenylbutyrate (Drug); Arginine (Drug)
Age
Pediatric, Adult, Older Adult · 5+ yrs
Sex
All
Sponsor
Brendan Lee
Primary completion
May 2011

Outcome Measures

OutcomeResultp-value
PRIMARY
Measures of Liver Function: AST and ALT
36.2; 52; 31.7; 57.86
PRIMARY
Measures of Liver Function: PT and PTT
14.25; 13.8; 30.91; 30.98
PRIMARY
Measures of Liver Function: Coagulation Factors
222.22; 229.77; 105.33; 98.36
PRIMARY
Measures of Liver Function: INR
14.2; 13.8
SECONDARY
Argininosuccinic Acid Levels
69; 53
SECONDARY
Arginine Levels
129; 53
SECONDARY
Urea Production Rate
215; 97

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
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00345605). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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