Nitric Oxide Supplementation in Argininosuccinic Aciduria
| Status: | Recruiting |
|---|---|
| Healthy: | No |
| Age Range: | 8 - 64 |
| Updated: | 1/20/2018 |
| Start Date: | September 2014 |
| End Date: | October 2018 |
| Contact: | Mary A Mullins, BSN |
| Email: | mullins@bcm.edu |
| Phone: | (832)822-4263 |
Nitric Oxide Supplementation as a Therapeutic Intervention in Argininosuccinic Aciduria
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.
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.
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.
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.
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
We found this trial at
1
site
6621 Fannin St
Houston, Texas 77030
Houston, Texas 77030
(832) 824-1000
Principal Investigator: Sandesh CS Nagamani, MD, FACMG
Texas Children's Hospital Texas Children's Hospital, located in Houston, Texas, is a not-for-profit organization whose...
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