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Nitric Oxide Supplementation in Argininosuccinic Aciduria

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02252770
Recruitment Status : Completed
First Posted : September 30, 2014
Last Update Posted : January 18, 2020
Information provided by (Responsible Party):
Sandesh Chakravarthy Sreenath Nagamani, Baylor College of Medicine

Brief 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.

Condition or disease Intervention/treatment Phase
Argininosuccinic Aciduria Argininosuccinate Lyase Deficiency Urea Cycle Disorders Dietary Supplement: Nitric oxide supplement Dietary Supplement: Placebo Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Nitric Oxide Supplementation as a Therapeutic Intervention in Argininosuccinic Aciduria
Study Start Date : September 2014
Actual Primary Completion Date : May 2018
Actual Study Completion Date : May 2018

Arm Intervention/treatment
Active Comparator: Nitric oxide supplement arm
During this arm, subjects will receive a lozenge with nitric oxide supplement
Dietary Supplement: Nitric oxide supplement
Each active comparator supplement is an all natural nitric oxide supplement. Subjects will take one lozenge twice a day.

Placebo Comparator: Placebo Arm
During this arm, subjects will receive placebo
Dietary Supplement: Placebo
Placebo will not contain nitric oxide supplement.

Primary Outcome Measures :
  1. Vascular endothelial function as assessed by FMD of brachial artery [ Time Frame: 2 weeks ]
    The primary outcome measures will be vascular endothelial function as assessed by the flow mediated dilatation (FMD) of the brachial artery measured by Doppler ultrasound.

Information from the National Library of Medicine

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Ages Eligible for Study:   8 Years to 64 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • A confirmed diagnosis of ASA based on biochemical, enzymatic, or genetic testing
  • Capable of completing study procedures
  • History of compliance with diet and treatment

Exclusion Criteria:

  • An active infection (viral or bacterial), any condition(s) that may precipitate a metabolic decompensation
  • A hypersensitivity to nitrite
  • A serum creatinine > 1.5 times above the normal
  • A clinical or laboratory abnormality of Grade 3 or greater according to the CTCAE V4.0 (except elevations of AST or ALT which are a part of the disease) which in the view of the Investigator compromises safety

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02252770

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United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030
Sponsors and Collaborators
Baylor College of Medicine
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Principal Investigator: Sandesh CS Nagamani, MD, FACMG Baylor College of Medicine
Additional Information:
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Responsible Party: Sandesh Chakravarthy Sreenath Nagamani, Assistant Professor, Baylor College of Medicine Identifier: NCT02252770    
Other Study ID Numbers: H-33236
First Posted: September 30, 2014    Key Record Dates
Last Update Posted: January 18, 2020
Last Verified: January 2020
Keywords provided by Sandesh Chakravarthy Sreenath Nagamani, Baylor College of Medicine:
Additional relevant MeSH terms:
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Urea Cycle Disorders, Inborn
Argininosuccinic Aciduria
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Amino Acid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Nitric Oxide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Free Radical Scavengers
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Vasodilator Agents
Protective Agents