5114: Effect of Nitric Oxide (NO) Supplementation on Neurocognitive Measures in Argininosuccinate Lyase Deficiency (ASLD)

Status: Recruiting

Study Summary

The purpose of this study is to find out if adding nitric oxide supplement to your diet will help you remember things better and solve problems better. In this study you will be given nitric oxide supplement and a placebo (sugar pill). The study doctors think that the medication may improve some aspects of your functioning. The placebo would not be expected to improve your health. The doctors will conduct tests to see how you do with the medication and the placebo.

For Diseases:

  • Argininosuccinate Lyase Deficiency (ASLD)

Background

Much of the body including the organs and muscles are made up of protein. The building blocks of protein are amino acids. These amino acids join together to form all the protein in the body. To keep healthy, the body is always making new protein and breaking down old protein that has become damaged or old. The body must also break down the protein we eat into a form it can use.

When protein is broken down, a substance called nitrogen is formed. Normally the body deals with this nitrogen by combining it with other things to make a harmless substance called urea through a process called the urea cycle. People with urea cycle disorders are not able to make as much of this urea from nitrogen, and because of this, can have too much nitrogen in the form of ammonia in their blood. This build-up of ammonia can harm them.

Patients with Argininosuccinate Lyase Deficiency (ASLD) usually have reduced amounts of the amino acid arginine and nitric oxide (NO) in their bodies. Arginine and nitric oxide are important substances thought to be involved in many functions of the body. In this study we want to see if a dietary supplement of nitric oxide will have any benefits on functions of the brain.

The objectives of this study are:

  • To evaluate the effect of the NO supplement, Neo-ASA, on brain functioning over time in these areas: general cognition, memory, executive functioning, and fine motor functioning.
  • To evaluate the safety of treatment of individuals with ASLD with Neo-ASA
  • To evaluate the effects of Neo-ASA supplementation on liver injury and function.

About this Study

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.

Study procedures

This study will entail 4 visits to the clinical research center and 2 laboratory draws at a facility close to the place of residence of the subject over the duration of the entire study.

Week 1 visit procedures, treatment period 1

  • Obtain informed consent
  • Measure vital signs - heart rate, blood pressure, respiratory rate, and body temperature
  • Measure height and weight
  • Record medical history
  • Perform physical examination
  • Collect blood sample for laboratory tests (Safety: complete blood count (CBC), comprehensive metabolic panel (CMP), ammonia; Research laboratory tests: nitrite, nitrate, and biochemical tests)
  • Collect urine sample for laboratory test (Safety: urine pregnancy test for women of child- bearing age)
  • Complete checklist for inclusion and exclusion criteria for enrollment
  • Perform neuropsychological testing
  • Blood may be collected establish lymphoblast culture *
  • Skin biopsy may be performed to establish a fibroblast culture *
  • Randomization for treatment assignment by Investigational Pharmacy Services of Texas Children’s Hospital
  • Administer medication and monitor for 2 hours

Week 6 laboratory procedures, treatment period 1

  • Collect blood sample for laboratory tests (Safety: complete blood count (CBC) and comprehensive metabolic panel (CMP))
  • Document adverse events
  • Document concomitant medications

Week 12, follow up over telephone, treatment period 1

  • Document adverse events
  • Document concomitant medications

Week 24 visit study procedures, treatment period 1

  • Measure vital signs - heart rate, blood pressure, respiratory rate, and body temperature
  • Measure height and weight
  • Record medical history
  • Perform physical examination
  • Collect blood sample for laboratory tests (Safety: complete blood count (CBC), comprehensive metabolic panel (CMP), ammonia; Research laboratory tests: nitrite, nitrate, and biochemical tests)
  • Perform neuropsychological testing

Following a washout period of 8 weeks, study procedures for treatment arm 2 will be initiated

Week 1 visit procedures, treatment period 2

  • Measure vital signs - heart rate, blood pressure, respiratory rate, and body temperature
  • Measure height and weight
  • Record medical history
  • Perform physical examination
  • Collect blood sample for laboratory tests (Safety: complete blood count (CBC), comprehensive metabolic panel (CMP), ammonia; Research laboratory tests: nitrite, nitrate, and biochemical tests)
  • Collect urine sample for laboratory test (Safety: urine pregnancy test for women of child- bearing age)
  • Perform neuropsychological testing
  • Administer medication for treatment period 2 and monitor for 2 hours

Week 6 laboratory procedures, treatment period 2

  • Collect blood sample for laboratory tests (Safety: complete blood count (CBC) and comprehensive metabolic panel (CMP)
  • Document adverse events
  • Document concomitant medications

Week 12, follow up over telephone, treatment period 2

  • Document adverse events
  • Document concomitant medications

Week 24 visit study procedures, treatment period 2

  • Measure vital signs - heart rate, blood pressure, respiratory rate, and body temperature
  • Measure height and weight
  • Record medical history
  • Perform physical examination
  • Collect blood sample for laboratory tests (Safety: complete blood count (CBC), comprehensive metabolic panel (CMP), ammonia; Research laboratory tests: nitrite, nitrate, and biochemical tests)
  • Perform neuropsychological testing

To be eligible to participate, you must:

  • Be Age > 6 and <50 years
  • Be Diagnosis of ASLD confirmed by biochemical OR enzymatic OR genetic testing
  • Have a history of compliance with diet and treatment
  • Negative pregnancy test and ability to use birth control method for the entire duration of the study (if the subject is of child-bearing potential)
  • Males who enroll in the study (and their partners) should argee to use an acceptable form of birth control for the entire duration of the study

You are not eligible to participate if:

  • You have a clinical or laboratory abnormality of Grade 3 or greater according to the CTCAE (or for conditions not covered by the CTCAE, a severe or life-threatening toxicity) at enrollment which, in the view of the investigator compromises safety. (Elevated plasma levels of aspartate and alanine aminotransferases, or low serum potassium will not be considered as exclusion criteria as these are phenotypic manifestations of ASLD.)
  • You have a known hypersensitivity to Neo-ASA or nitrite
  • You are currently being administered other investigational agents

How to Join

In order to participate in a study, you must personally contact the study coordinator by phone or by e-mail. Please use the information below to ask about participation.

Texas Children’s Hospital – Baylor College of Medicine
Mary A. Mullins BSN, RN, CCRC
Phone: 832-822-4263
Email: mullins@bcm.edu

OR

Saima Ali, RN, FNP-C
Phone: 832-822-4183
Email: sma1@bcm.edu

 

Total Enrolled

 6