Clinical Trial: Nitric Oxide Supplementation on Neurocognitive Functions in Patients With ASLD

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Effect of Nitric Oxide (NO) Supplementation on Neurocognitive Measures in Argininosuccinate Lyase Deficiency (ASLD)

Brief 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 Summary:

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, an
Sponsor: Baylor College of Medicine

Current Primary Outcome:

• Delis-Kaplan Executive Function System - Tower subtest [ Time Frame: 24 weeks ]
  Change in the scores from baseline to 24 weeks with drug vs placebo
• Stanford-Binet - 4th Edition: Bead Memory and Sentence Memory subtests [ Time Frame: 24 weeks ]
  Change in the scores from baseline to 24 weeks with drug vs placebo
• Grip Strength [ Time Frame: 24 weeks ]
  Change in the scores from baseline to 24 weeks with drug vs placebo
• Grooved Pegboard [ Time Frame: 24 weeks ]
  Change in the scores from baseline to 24 weeks with drug vs placebo
• Wechsler Intelligence Scale for Children OR Wechsler Adult Intelligence Scale - 4th Edition (in subjects > 16 years of age) [ Time Frame: 24 weeks ]
  Change in the scores from baseline to 24 weeks with drug vs placebo
• Tower of London Test [ Time Frame: 24 weeks ]
  Change in the scores from baseline to 24 weeks with drug vs placebo
• Conners Continuous Performance Test - 3rd Edition Conners Continuous Performance Test - 3rd Edition [ Time Frame: 24 weeks ]
  Change in the scores from baseline to 24 weeks with drug vs placebo

Original Primary Outcome: Same as current

Current Secondary Outcome:

Original Secondary Outcome:

Information By: Baylor College of Medicine

Dates:
Date Received: February 10, 2017
Date Started: April 15, 2017
Date Completion: December 31, 2023
Last Updated: February 21, 2017
Last Verified: February 2017