Nitric Oxide Supplementation in Argininosuccinic Aciduria
Condition: Argininosuccinic Aciduria; Argininosuccinate Lyase Deficiency; Urea Cycle Disorders
MeSH terms: Urea Cycle Disorders, Inborn; Argininosuccinic Aciduria
Study type: Interventional

Summary: 
      This is a study involving a dietary supplement. Patients with argininosuccinic aciduria will
      be randomly assigned to receive either a nitric oxide dietary supplement or placebo for 2
      weeks, and then crossed-over to receive the other treatment for two weeks.

      The investigators expect to see that : 1) Patients with ASA will have a decreased ability for
      their arteries to dilate due to nitric oxide deficiency, 2) Treatment of ASA with the nitric
      oxide supplement will improve the ability of their arteries to dilate, and 3) Through the
      testing of subjects' fibroblasts (cells in connective tissue that produce collagen and other
      fibers), the investigators hope to predict which patients may respond NO supplementation.
    

Detailed description: 
      The investigators will perform a double blind, randomized, placebo-controlled, crossover
      study of NO supplementation in ASA patients assessing endothelial function and blood pressure
      as primary endpoints, and markers of nitric oxide production as exploratory endpoints.

      Subjects will receive a nitrite-restricted diet prior to the start and during the trial
      period. The dietary protein prescriptions will not be altered. After screening, informed
      consent, subjects will undergo study procedures at the Clinical Research Center (CRC) at
      Texas Children's Hospital, Houston, TX.

      Safety laboratories will be performed. Fibroblast and lymphoblast cultures will be
      established for subsequent studies.A baseline assessment of the vascular endothelial NO
      production and function will be assessed using FMD of brachial artery using standard
      techniques (1). Subjects will be randomized to receive either dietary nitric oxide supplement
      or placebo for 2 weeks, and then crossed-over to receive the other treatment for two weeks.
      The Investigational Pharmacy Services at Texas Children's Hospital will assign the initial
      treatment group randomly in a 1:1 ratio using established randomization procedures. Following
      randomization, subjects will be receive either Neo40® 40 mg/kg/day in two divided doses) or
      placebo for 14 days. This dose is the dietary supplemental dose and was well-tolerated in the
      investigators proof of concept treatment subject as well as other clinical studies in
      cardiovascular disease. Subjects will return on day 14 to the CRC where they will undergo
      assessment of FMD of the brachial artery, repeated BP measurements, and assay of NO status.
      The subjects will then be crossed over to receive the alternative treatment and the study
      procedures will be repeated in identical fashion to the initial arm.
    

Intervention name(s): Nitric oxide supplement; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Each active comparator supplement is an all natural nitric oxide supplement. Subjects will take one lozenge twice a day.; Placebo will not contain nitric oxide supplement.
Intervention MeSH terms: Nitric Oxide
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: ASA; ASLD; UCD