Argininosuccinic AciduriaNCT02252770
Nitric Oxide Supplementation in Argininosuccinic Aciduria
A study testing Nitric oxide supplement in people with Argininosuccinic Aciduria and Argininosuccinate Lyase Deficiency, run by Baylor College of Medicine at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 8 to 64 years
- Conditions the study is for
- Argininosuccinic Aciduria, Argininosuccinate Lyase Deficiency, Urea Cycle Disorders
- What is being tested?
- Nitric oxide supplement
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2014to May 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 to 64 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- A confirmed diagnosis of ASA based on biochemical, enzymatic, or genetic testing
- Capable of completing study procedures
- History of compliance with diet and treatment
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the detailed description
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.
- Being tested
- Nitric oxide supplement, Placebo
- Keywords
- ASA, ASLD, UCD
- Medical subject headings
- Argininosuccinic Aciduria, Urea Cycle Disorders, Inborn
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nitric oxide supplementDietary supplement
Each active comparator supplement is an all natural nitric oxide supplement. Subjects will take one lozenge twice a day.
PlaceboDietary supplement
Placebo will not contain nitric oxide supplement.
| Study group | Role | What they receive |
|---|---|---|
| Nitric oxide supplement arm | Active comparator | During this arm, subjects will receive a lozenge with nitric oxide supplement Receives: Dietary Supplement: Nitric oxide supplement |
| Placebo Arm | Placebo comparator | During this arm, subjects will receive placebo Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2014 (estimated)
- Study startSep 2014
- Primary completionMay 2018
- Study completionMay 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Argininosuccinic AciduriaStudies of the same condition, open and under way.
- More trials run by Baylor College of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sandesh Chakravarthy Sreenath Nagamani, Baylor College of Medicine
- Investigators
- Sandesh CS Nagamani, MD, FACMG, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02252770
- Sponsor's protocol ID
- H-33236
- Status last verified
- Jan 2020
- First submitted
- 25 Sep 2014
- Last updated
- 18 Jan 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 11788217Nagamani 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.
PubMed 22541557Nagamani 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.
PubMed 22841516
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nitric Oxide Supplementation as a Therapeutic Intervention in Argininosuccinic Aciduria
- ClinicalTrials.gov ID
- NCT02252770
- Acronym / sponsor ID
- H-33236
- Keywords
- ASA, ASLD, UCD
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Study start
- Sep 2014
- Primary completion
- May 2018 (actual)
- Study completion
- May 2018 (actual)
- First posted
- 30 Sep 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nitric oxide supplement arm | Active comparator | Dietary Supplement: Nitric oxide supplementDuring this arm, subjects will receive a lozenge with nitric oxide supplement |
| Placebo Arm | Placebo comparator | Dietary Supplement: PlaceboDuring this arm, subjects will receive placebo |
Who may qualify
- Ages
- 8 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- A confirmed diagnosis of ASA based on biochemical, enzymatic, or genetic testing
- Capable of completing study procedures
- History of compliance with diet and treatment
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nitric oxide supplementEach active comparator supplement is an all natural nitric oxide supplement. Subjects will take one lozenge twice a day. | Dietary supplement | Nitric oxide supplement arm |
| PlaceboPlacebo will not contain nitric oxide supplement. | Dietary supplement | Placebo Arm |
Primary outcome
Vascular endothelial function as assessed by FMD of brachial artery
Time frame: 2 weeks
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2020.
- Background: PubMed 11788217Corretti 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.
- Background: PubMed 22541557Nagamani 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.
- Background: PubMed 22841516Nagamani 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.
- Sandesh CS NagamaniLink provided by the sponsor.
- Baylor College of Medicine, Department of Molecular and Human GeneticsLink provided by the sponsor.
Related trials for Argininosuccinic Aciduria
RecruitingPhase 1/2
Phase 1/2 Study of KRRO-121 in Healthy Volunteers and Patients With UCD
Urea Cycle Disorders, Inborn, Urea Cycle Disorders
Active, not recruitingObservational study
Early Check: Expanded Screening in Newborns
Spinal Muscular Atrophy, Fragile X Syndrome
Active, not recruitingObservational study
Liver Disease in Urea Cycle Disorders
Urea Cycle Disorder, Ornithine Transcarbamylase Deficiency
RecruitingObservational study
Hepatic Histopathology in Urea Cycle Disorders
Urea Cycle Disorder, Ornithine Transcarbamylase Deficiency
RecruitingObservational study
Systemic Biomarkers of Brain Injury From Hyperammonemia
Urea Cycle Disorder, Organic Acidemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sandesh CS Nagamani, MD, FACMG principal investigator
Baylor College of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Nitric oxide supplement in people with Argininosuccinic Aciduria and Argininosuccinate Lyase Deficiency, run by Baylor College of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Vascular endothelial function as assessed by FMD of brachial artery (time frame: 2 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02252770, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2020.