Nitric Oxide Supplementation on Neurocognitive Functions in Patients With ASLD

NCT03064048 | Completed DMC

• 1 other identifier: H-40143
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Argininosuccinate Lyase Deficiency; Urea Cycle Disorder; Urea Cycle Disorders, Inborn; Argininosuccinic Aciduria

Keywords

Argininosuccinate Lyase Deficiency; Urea Cycle Disorder

Outcome Measures

Primary Outcomes (7)

• Delis-Kaplan Executive Function System - Tower subtest

  Change in the scores from baseline to 24 weeks with drug vs placebo

  24 weeks

• Stanford-Binet - 4th Edition: Bead Memory and Sentence Memory subtests

  Change in the scores from baseline to 24 weeks with drug vs placebo

  24 weeks

• Grip Strength

  Change in the scores from baseline to 24 weeks with drug vs placebo

  24 weeks

• Grooved Pegboard

  Change in the scores from baseline to 24 weeks with drug vs placebo

  24 weeks

• Wechsler Intelligence Scale for Children OR Wechsler Adult Intelligence Scale - 4th Edition (in subjects > 16 years of age)

  Change in the scores from baseline to 24 weeks with drug vs placebo

  24 weeks

• Tower of London Test

  Change in the scores from baseline to 24 weeks with drug vs placebo

  24 weeks

• Conners Continuous Performance Test - 3rd Edition Conners Continuous Performance Test - 3rd Edition

  Change in the scores from baseline to 24 weeks with drug vs placebo

  24 weeks

Study Arms (2)

Neo-ASA

ACTIVE COMPARATOR

During this arm the participant will receive a lozenge with nitric oxide as a dietary supplement twice daily.

Dietary Supplement: Neo-ASA

Placebo

PLACEBO COMPARATOR

During this arm the participant will receive a lozenge which will not contain nitric oxide as a dietary supplement twice daily.

Dietary Supplement: Placebo

Interventions

Neo-ASA DIETARY_SUPPLEMENT

Dietary supplement with nitric oxide in the form of a lozenge called Neo-ASA.

Neo-ASA

Placebo DIETARY_SUPPLEMENT

Dietary supplement with no nitric oxide in the form of a lozenge to look and taste like the dietary supplement Neo-ASA

Placebo

Eligibility Criteria

• Age: 6 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age \> 6 and \<50 years
• Diagnosis of ASLD confirmed by biochemical OR enzymatic OR genetic testing
• Has 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 may not qualify if:

• Known hypersensitivity to Neo-ASA or nitrite
• Individuals currently being administered other investigational agents

Sponsors & Collaborators

• Baylor College of Medicine: lead
• Rare Diseases Clinical Research Network: collaborator
• Neogenis Laboratories: collaborator

Study Sites (1)

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Related Publications (3)

• 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 SCS, Burrage LC, Lee B. Argininosuccinate Lyase Deficiency. 2011 Feb 3 [updated 2025 Aug 14]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK51784/

  PMID: 21290785 BACKGROUND

• Erez A, Nagamani SC, Shchelochkov OA, Premkumar MH, Campeau PM, Chen Y, Garg HK, Li L, Mian A, Bertin TK, Black JO, Zeng H, Tang Y, Reddy AK, Summar M, O'Brien WE, Harrison DG, Mitch WE, Marini JC, Aschner JL, Bryan NS, Lee B. Requirement of argininosuccinate lyase for systemic nitric oxide production. Nat Med. 2011 Nov 13;17(12):1619-26. doi: 10.1038/nm.2544.

  PMID: 22081021 BACKGROUND

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 C Nagamani, M.D.

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

• Brendan Lee, M.D., PhD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Randomization for treatment assignment is by the providing Institution's Investigational Pharmacy Services.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Active Comparator: Nitric oxide supplement Active Comparator will l not contain nitric oxide supplement. Placebo Comparator: Placebo Placebo will not contain nitric oxide supplement.

Study Record Dates

• First Submitted: February 10, 2017
• First Posted: February 24, 2017
• Study Start: September 15, 2017
• Primary Completion: January 31, 2023
• Study Completion: January 31, 2023
• Last Updated: February 27, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share

Locations

US (1)