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 : January 18, 2018
|Condition or disease||Intervention/treatment||Phase|
|Argininosuccinate Lyase Deficiency Urea Cycle Disorder Urea Cycle Disorders, Inborn Argininosuccinic Aciduria||Dietary Supplement: Neo-ASA Dietary Supplement: Placebo||Not Applicable|
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 :||Interventional (Clinical Trial)|
|Estimated Enrollment :||16 participants|
|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.|
|Official Title:||Effect of Nitric Oxide (NO) Supplementation on Neurocognitive Measures in Argininosuccinate Lyase Deficiency (ASLD)|
|Actual Study Start Date :||September 15, 2017|
|Estimated Primary Completion Date :||January 31, 2020|
|Estimated Study Completion Date :||December 31, 2023|
Active Comparator: Neo-ASA
During this arm the participant will receive a lozenge with nitric oxide as a dietary supplement twice daily.
Dietary Supplement: Neo-ASA
Dietary supplement with nitric oxide in the form of a lozenge called 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.
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
- 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
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 ClinicalTrials.gov identifier (NCT number): NCT03064048
|Contact: Mary A Mullins, RNfirstname.lastname@example.org|
|Contact: Sandesh C Nagamani, M.D.||email@example.com|
|United States, Texas|
|Baylor College of Medicine||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Mary A Mullins, RN 823-822-4263 firstname.lastname@example.org|
|Principal Investigator: Sandesh C Nagamani, M.D.|
|Principal Investigator: Brendan Lee, M.D., PhD|
|Principal Investigator:||Sandesh C Nagamani, M.D.||Baylor College of Medicine|
|Principal Investigator:||Brendan Lee, M.D., PhD||Baylor College of Medicine|