Nitric Oxide Supplementation in Argininosuccinic Aciduria

NCT02252770 | Completed

• 1 other identifier: H-33236
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Argininosuccinic Aciduria; Argininosuccinate Lyase Deficiency; Urea Cycle Disorders

Keywords

ASA; ASLD; UCD

Outcome Measures

Primary Outcomes (1)

• Vascular endothelial function as assessed by FMD of brachial artery

  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.

  2 weeks

Study Arms (2)

Nitric oxide supplement arm

ACTIVE COMPARATOR

During this arm, subjects will receive a lozenge with nitric oxide supplement

Dietary Supplement: Nitric oxide supplement

Placebo Arm

PLACEBO COMPARATOR

During this arm, subjects will receive placebo

Dietary Supplement: Placebo

Interventions

Nitric oxide supplement DIETARY_SUPPLEMENT

Each active comparator supplement is an all natural nitric oxide supplement. Subjects will take one lozenge twice a day.

Nitric oxide supplement arm

Placebo DIETARY_SUPPLEMENT

Placebo will not contain nitric oxide supplement.

Placebo Arm

Eligibility Criteria

• Age: 8 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Baylor College of Medicine: lead

Study Sites (1)

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Related Publications (3)

• Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, Deanfield J, Drexler H, Gerhard-Herman M, Herrington D, Vallance P, Vita J, Vogel R; International Brachial Artery Reactivity Task Force. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol. 2002 Jan 16;39(2):257-65. doi: 10.1016/s0735-1097(01)01746-6.

  PMID: 11788217 BACKGROUND

• Nagamani SC, Campeau PM, Shchelochkov OA, Premkumar MH, Guse K, Brunetti-Pierri N, Chen Y, Sun Q, Tang Y, Palmer D, Reddy AK, Li L, Slesnick TC, Feig DI, Caudle S, Harrison D, Salviati L, Marini JC, Bryan NS, Erez A, Lee B. Nitric-oxide supplementation for treatment of long-term complications in argininosuccinic aciduria. Am J Hum Genet. 2012 May 4;90(5):836-46. doi: 10.1016/j.ajhg.2012.03.018. Epub 2012 Apr 26.

  PMID: 22541557 BACKGROUND

• Nagamani SC, Lee B, Erez A. Optimizing therapy for argininosuccinic aciduria. Mol Genet Metab. 2012 Sep;107(1-2):10-4. doi: 10.1016/j.ymgme.2012.07.009. Epub 2012 Jul 20.

  PMID: 22841516 BACKGROUND

Related Links

• Sandesh CS Nagamani
• Baylor College of Medicine, Department of Molecular and Human Genetics

MeSH Terms

Conditions

Argininosuccinic Aciduria; Urea Cycle Disorders, Inborn

Condition Hierarchy (Ancestors)

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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Sandesh CS Nagamani, MD, FACMG

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: September 25, 2014
• First Posted: September 30, 2014
• Study Start: September 1, 2014
• Primary Completion: May 1, 2018
• Study Completion: May 1, 2018
• Last Updated: January 18, 2020

Record last verified: 2020-01

Locations

US (1)