UCD Research Study Comparative Effectiveness of Two Treatments

Drs. Juan Marini, Sandesh Nagamani, and members of Dr. Brendan Lee’s research team, want to determine the effectiveness of sodium phenylbutyrate (Buphenyl™) vs. sodium benzoate in the treatment of urea cycle disorders. This research study will be conducted at Baylor College of Medicine in Houston, Texas.

Our goal is to help doctors and researchers better understand how well these medications work in controlling ammonia in patients with urea cycle disorders. We will study and compare how effectively sodium phenylbutyrate (Buphenyl™) and sodium benzoate help excrete nitrogen in patients with urea cycle disorders.

The research study is sponsored by the NIH/Rare Disease Clinical Research Network (RDCRN) Urea Cycle Disorders Consortium.
To be eligible to participate in the study you must:

  • Be at least 18 years old with a known diagnosis of urea cycle disorder, asymptomatic, metabolically stable and not taking an ammonia scavenger drug.
  • Travel to Baylor College of Medicine in Houston, Texas.
  • Maintain the diet and treatment plan prescribed while you are in the study.

All procedures (testing) and study drug are provided to you at no cost.


This is a study to compare the efficiency of phenylbutyrate (PBA) and sodium benzoate to conjugate nitrogenous compounds. Subjects will be studied during two treatment arms. Each arm will be completed over four days with a washout period of at least one week between treatment arms. As this is not a blinded study, randomization will be performed by PI or Co-PI. Subjects who receive PBA in the first treatment arm will receive sodium benzoate during the second. There is no placebo arm, and no control subjects will be studied.

Inclusion Criteria:

Asymptomatic (defined as metabolically stable) adult, ammonia scavenger drug-naive patients with urea cycle disorders may participate in this study.

Exclusion Criteria:

Subjects with (a) a history of frequent dietary protein intolerance, (b) a history of chronic or acute liver diseases which may result in altered hepatic synthetic capacity (e.g., hepatitis), (c) acute or chronic disease or on medications that in the opinion of the clinical investigators will interfere with the measurements (e.g., drugs which may have hepatotoxicity as potential side effects), (d) a physical disability that will interfere with their ability to either conform to the dietary regimes or undergo the isotopic infusions, (e) pregnancy or recent (<6 months)/current lactation, (f) intercurrent evidence of significant hyperammonemia (more than 100 µmol/L), (g) any clinical abnormality of Grade 3 or greater according to the Common Terminology Criteria for Adverse Events v.4.0 (CTCAE), (h) any condition(s) not covered by the CTCAE, or a severe or life-threatening toxicity at screening, will be excluded from the study. Subjects taking ammonia scavenger medications will not be enrolled.

Study Procedures

          Arm 1, Day 1 is an early morning outpatient visit to the TCH Clinical Care Center. After informed consent has been obtained, fasting safety labs for baseline measurements of complete blood count, comprehensive metabolic panel, and plasma ammonia will be drawn and sent to the Texas Children’s Hospital Department of Pathology. A urine pregnancy test will be performed for all female subjects of childbearing potential to rule out pregnancy. Vital signs will be performed and height and weight measured. Medical history review and physical examination will be performed. Following a review of baseline lab results, concomitant medications, medical history and physical examination assessments, the clinical investigator with determine if subject qualifies for the study. Subjects will be prescribed either sodium benzoate (5.5 g/m2/day divided into three equal doses per day with a maximum dose 12 g/day) or PBA (7.15 g/m2/day divided into three equal doses per day with a maximum dose of 20 g/day). Subjects will be instructed to take the study medication with meals (08:00 breakfast; 13:00 lunch; 19:00 dinner) until they return on Day 4. The Investigational Pharmacy Service at Texas Children’s Hospital will dispense the study medication.

Subjects will be given their first dose of study medication in the clinic with breakfast and monitored for one hour before being discharged. Subjects will continue a diet of 0.8 gm/kg protein and 32 kcal/kg per day by only eating boxed meals prepared at the CNRC. Subjects may choose to receive all their meals at discharge or return daily to pick up meals.

On Day 4,subjects will be admitted to the Metabolic Research Unit (MRU) of the Children’s Nutrition Research Center. At 7:00 AM, an intravenous catheter will be placed in the hand or arm for isotope infusion and blood collection. At 7:30 AM, a fasting, baseline blood sample will be drawn for the determination of plasma amino acids, ammonia and urea concentrations, and background isotopic enrichments. Plasma concentrations of PBA or benzoate, as applicable, and their metabolites will be drawn, and a urine sample will be collected for baseline concentrations of ammonia and urea. At 8:00 AM half of the daily dietary allowance of protein will be provided in a meal of food, Ensure and 15N labeled Spirulina (30 mg/kg) which will result in a dietary enrichment of ~6 mole percent excess. This will be ingested in <30 minutes. At 8:30 AM, subjects will receive a dose of PBA or benzoate. A urea tracer of [13C18O]urea will be given intravenously over 5 minutes in 25 ml normal saline as a single bolus. This will be followed by a 10 ml normal saline flush. Blood samples for isotopic enrichments will be collected every 30 minutes for 3 hours (9:00, 9:30, 10:00, 10:30, 11:00 and 11:30) and then hourly for 5 hours (12:30, 13:30, 14:30, 15:30, and 16:30). A low protein snack will be offered at lunchtime. Three separate urine samples will be collected throughout the Day 4 studies. After sample collection is completed, subjects will be discharged from the MRU.

The patients will return home and after a washout period of at least 1 week, they will come back for Arm 2 where the study procedures will be identical to those in Arm 1, except the medication given. If they have received benzoate in Arm 1, they will receive phenylbutyrate in Arm 2 and vice versa.

To learn more about participating in the study, contact:
Mary Mullins, Study Coordinator
Phone: (832)822-4263
Email:  This e-mail address is being protected from spambots. You need JavaScript enabled to view it