Nitric Oxide Supplementation on Neurocognitive Functions in Patients With ASLD
Condition: Argininosuccinate Lyase Deficiency; Urea Cycle Disorder; Urea Cycle Disorders, Inborn; Argininosuccinic Aciduria
MeSH terms: Urea Cycle Disorders, Inborn; Argininosuccinic Aciduria
Study type: Interventional

Summary: 
      This is a study involving a dietary supplement. Patients with argininosuccinate lyase
      deficiency (ASLD) will be randomly assigned to receive either a nitric oxide dietary
      supplement or placebo for 24 weeks, and then crossed-over to receive the other treatment for
      24 weeks. The investigators will assess the effects of the supplement in domains of general
      cognition, memory, executive functioning, and fine motor functioning in individuals with
      ASLD.
    

Detailed description: 
      Argininosuccinate lyase deficiency (ASLD; also known as argininosuccinic aciduria) is the
      second most common urea cycle disorder (UCD) and accounts for 15-20% of all disorders of
      ureagenesis. Individuals with ASLD can have unique clinical and physiologic characteristics
      as compared to other UCDs. Previous work from the members of the UCDC have shown that in
      spite of having fewer episodes of hyperammonemia as compared to those with proximal blockade
      of the urea cycle, individuals with ASLD can develop intellectual and learning disabilities.
      Neurocognitive deficits have been observed even in individuals without any documented
      hyperammonemia. Furthermore, hepatic abnormalities including hepatomegaly, hepatic injury,
      fibrosis and even frank cirrhosis, and vascular issues like hypertension are well known in
      the disorder. Previous work from the members of the UCDC has demonstrated a tissue- and
      molecular-specific role for ASL in the generation of NO. ASL is not only required for the
      synthesis of L-arginine, the substrate for the synthesis of NO, but is also an integral
      member of a complex that is critical for synthesis of NO from arginine. Loss of ASL can thus
      lead to systemic and tissue-specific NO deficiencies, which could potentially contribute to
      the complex phenotype including the neurocognitive deficits. A rational therapeutic option
      would hence be to use a NOS-independent NO supplement.

      The purpose of this study is to determine whether a dietary NO supplement, Neo-ASA, would
      improve general cognition, memory, executive functioning, fine motor functioning, and
      attention in individuals with ASLD. In this single-center trial, double-blind, randomized,
      placebo-controlled, crossover study, individuals with ASLD will be assigned to receive a
      medication containing NO dietary supplement for 24 weeks and a placebo for 24 weeks. General
      cognition, memory, executive functioning, and fine motor functioning will be assessed and
      compared at the end of treatment with placebo and Neo-ASA.
    

Intervention name(s): Neo-ASA; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Dietary supplement with nitric oxide in the form of a lozenge called Neo-ASA.; Dietary supplement with no nitric oxide in the form of a lozenge to look and taste like the dietary supplement Neo-ASA
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Active Comparator: Nitric oxide supplement Active Comparator will l not contain nitric oxide supplement.
Placebo Comparator: Placebo Placebo will not contain nitric oxide supplement.
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Argininosuccinate Lyase Deficiency; Urea Cycle Disorder