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Nitric Oxide Supplementation on Neurocognitive Functions in Patients With ASLD

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03064048
Recruitment Status : Recruiting
First Posted : February 24, 2017
Last Update Posted : September 11, 2019
Sponsor:
Collaborators:
Rare Diseases Clinical Research Network
Neogenis Laboratories
Information provided by (Responsible Party):
Sandesh Chakravarthy Sreenath Nagamani, Baylor College of Medicine

Tracking Information
First Submitted Date  ICMJE February 10, 2017
First Posted Date  ICMJE February 24, 2017
Last Update Posted Date September 11, 2019
Actual Study Start Date  ICMJE September 15, 2017
Estimated Primary Completion Date January 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 21, 2017)
  • 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 Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Nitric Oxide Supplementation on Neurocognitive Functions in Patients With ASLD
Official Title  ICMJE 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 Description

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, and fine motor functioning will be assessed and compared at the end of treatment with placebo and Neo-ASA.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:

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

Placebo Comparator: Placebo Placebo will not contain nitric oxide supplement.

Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:
Randomization for treatment assignment is by the providing Institution's Investigational Pharmacy Services.
Primary Purpose: Treatment
Condition  ICMJE
  • Argininosuccinate Lyase Deficiency
  • Urea Cycle Disorder
  • Urea Cycle Disorders, Inborn
  • Argininosuccinic Aciduria
Intervention  ICMJE
  • Dietary Supplement: Neo-ASA
    Dietary supplement with nitric oxide in the form of a lozenge called Neo-ASA.
  • Dietary Supplement: Placebo
    Dietary supplement with no nitric oxide in the form of a lozenge to look and taste like the dietary supplement Neo-ASA
Study Arms  ICMJE
  • Active Comparator: Neo-ASA
    During this arm the participant will receive a lozenge with nitric oxide as a dietary supplement twice daily.
    Intervention: Dietary Supplement: Neo-ASA
  • Placebo Comparator: Placebo
    During this arm the participant will receive a lozenge which will not contain nitric oxide as a dietary supplement twice daily.
    Intervention: Dietary Supplement: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 21, 2017)
16
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2023
Estimated Primary Completion Date January 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Age > 6 and <50 years
  2. Diagnosis of ASLD confirmed by biochemical OR enzymatic OR genetic testing
  3. Has a history of compliance with diet and treatment
  4. 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)
  5. 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

Exclusion Criteria:

  1. 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.)
  2. Known hypersensitivity to Neo-ASA or nitrite
  3. Individuals currently being administered other investigational agents
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Years to 50 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Mary A Mullins, RN 832-822-4263 mullins@bcm.edu
Contact: Sandesh C Nagamani, M.D. nagamani@bcm.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03064048
Other Study ID Numbers  ICMJE H-40143
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: According to the policy of the National Institutes of Health (one of the study sponsors) research data may be put in a secure, limited-access database known as dbGaP. The data will include any genetic test results as well as other information about medical problems. There will be NO identifiers included (no name, data of birth, address, social security number, etc.). Access to this information is restricted by the National Institutes of Health. Only doctors and scientists who get approval from the National Institutes of Health can access this de-identified data.
Responsible Party Sandesh Chakravarthy Sreenath Nagamani, Baylor College of Medicine
Study Sponsor  ICMJE Baylor College of Medicine
Collaborators  ICMJE
  • Rare Diseases Clinical Research Network
  • Neogenis Laboratories
Investigators  ICMJE
Principal Investigator: Sandesh C Nagamani, M.D. Baylor College of Medicine
Principal Investigator: Brendan Lee, M.D., PhD Baylor College of Medicine
PRS Account Baylor College of Medicine
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP