Argininosuccinic AciduriaNCT01421888
The NIH UNI Study: Urea Cycle Disorders, Nutrition and Immunity
An observational study of Argininosuccinic Aciduria and Carbamoyl-Phosphate Synthase I Deficiency, run by National Human Genome Research Institute (NHGRI) at 1 site in United States.
Trial summary
Objectives: To study nutrition and immune system problems in people with urea cycle disorders. To study how people with urea cycle disorders and healthy volunteers respond to standard flu and/or hepatitis A vaccines. Read more about this study
- Who is it for?
- Ages 2 to 99 yearsHealthy volunteers can take part
- Conditions the study is for
- Argininosuccinic Aciduria, Carbamoyl-Phosphate Synthase I Deficiency, Citrullinemia
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Aug 2011to 17 Apr 2013
- Phase
- Observational
- 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 2 to 99 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Patients:
- Any gender and ethnicity age 2 years and older with a diagnosis of a urea cycle disorder are eligible to enroll in this protocol.
- Patients need to be medically and nutritionally managed by a local metabolic provider. If necessary, we will obtain written consent from the patient to review medical records from their home physician to confirm eligibility.
- Healthy Volunteers:
- Any gender and ethnicity age 2 years and older are eligible to enroll in this protocol.
- Have access to own personal medical provider <TAB>
Who cannot join
- Less than 2 years of age
- Inability to travel to NIH because of their medical condition
- Recent (6 month) history of vaccination or immune modulating drug
- Severe reactions to eggs and or latex
- History of severe reactions to previous immunizations (e.g. hives, rash, difficulty breathing)
- Persons without a personal medical provider
- Persons with current infections or under care of medical provider for an ongoing medical issue
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Objectives:
- To study nutrition and immune system problems in people with urea cycle disorders.
- To study how people with urea cycle disorders and healthy volunteers respond to standard flu and/or hepatitis A vaccines.
- To compare differences in nutrition and immune systems of people with urea cycle disorders with that of healthy volunteers.
Read more
Eligibility:
- Healthy males and females at least 2 years of age who are able to travel to the National Institutes of Health hospital in Bethesda, MD
- Males and females at least 2 years of age who have a urea cycle disorder and are able to travel to the National Institutes of Health hospital in Bethesda, MD.
Design:
For Patients with urea cycle disorder:
- Participants will spend 2 to 3 days in the National Institutes of Health hospital for the following tests:
- A physical exam and review of medical history
- Food log for 3 days before the start of the study
- Blood tests
- 24-hour urine collection
- Resting metabolism test
- DEXA scan imaging study of bones and body fat
- Participants who are old enough to do certain tasks by themselves (like dressing and eating) can choose to have the following extra tests:
- 24-hour metabolic room measurements
- BodPod(Registered Trademark) study to measure bones and body fat
- Participants may choose to have a flu shot and/ or Hepatitis A shot at the end of the study and will be monitored to check for possible side effects.
- Participants will return within 1 to 3 months for follow-up tests/immunizations.
For Healthy Volunteers:
- Participants will be seen at the outpatient clinics at the National Institutes of Health hospital for up to 2 visits for the following:
- Review food log completed 3 days before the start of the study
- Blood tests
- Participants may choose to have a flu shot and/ or Hepatitis A shot at the end of the study and will be monitored to check for possible side effects.
- Participants will return within 1 to 3 months for follow-up tests/immunizations.
- Review of second food log completed 3 days before second outpatient visit
Read the detailed description
Urea cycle disorders (UCD) are amongst the most frequent of the inborn errors of metabolism (IEM) and result from a block in the hepatic disposal of waste nitrogen from protein catabolism. Viral infections play a significant role in precipitating life-threatening acute hyperammonemic crises in UCD. The recent H1N1 influenza pandemic has placed this vulnerable population at significant risk. The standard of care for these patients is routine vaccination for seasonal and H1N1 influenza viruses. However, nutritional deficiencies and their underlying enzymopathy may affect the efficacy of vaccination.
Dietary management of urea cycle disorders includes dietary modification with protein restriction. Protein energy malnutrition, essential fatty acid deficiencies and micronutrient deficiencies due to restrictive dietary management have been reported in various inborn errors of metabolism. In general, dietary deficiencies and their effect on immune function are well documented.
In addition to the disposal of waste nitrogen, the urea cycle also generates arginine for various biologic functions. Depending on the site of the metabolic block, UCD patients are at risk for becoming systemically deficient in citrulline and arginine, with potential implications for the immune system. The immunomodulatory roles of the amino acids citrulline and arginine have been characterized in the context of nutritional deficiencies in disease states such as cancer and sepsis. Systemic infection may also deplete systemic citrulline and arginine, compounding an underlying deficiency in UCD. Cells of the immune system have a more direct relationship with the urea cycle: urea cycle enzymes arginosuccinate synthetase (ASS), arginosuccinate lyase (ASL) and arginase (ARG1) may also be components of leukocyte metabolism. Overall, general and specific nutritional deficiencies and enzymopathies affecting leukocyte metabolism may potentially affect vaccine efficacy. However, immune system function in experiments of nature such as UCD remains an understudied area.
In this protocol, we will clinically evaluate the nutritional/metabolic and immunologic states of patients with UCD or related disorders. Routine inpatient admissions will last 2-3 days and involve urine collection, blood drawing, radiological procedures, nutrition assessment and biometrics, and vaccination for combined seasonal/H1N1 influenza. Follow-up outpatient appointments will be scheduled at the end of the study period.
The study objectives will be to describe the nutritional and immune deficiencies seen, query for nutrition/enzymatic/immunologic correlations in this patient population, describe vaccine efficacy in this patient population, and search for new genes in rare families that have evidence for an unknown class of UCD. The population will consist of patients previously evaluated at NIH, physician referrals, and families directed to the study from clinicaltrials.gov as well as the National Urea Cycle Disorders Foundation. All patients will be evaluated at the NIH Clinical Center.
- Conditions
- Argininosuccinic Aciduria, Carbamoyl-Phosphate Synthase I Deficiency, Citrullinemia, Ornithine Carbamoyltransferase Deficiency, Hyperargininemia, N-Acetylglutamate Synthase Deficiency
- Keywords
- Immunity, Urea Cycle Disorder, Nutrition, Vaccination, Influenza
- Medical subject headings
- Argininosuccinic Aciduria, Citrullinemia, Ornithine Carbamoyltransferase Deficiency Disease, Hyperargininemia, N-acetyl glutamate synthetase deficiency, Urea Cycle Disorders, Inborn, Influenza, Human
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2011 (estimated)
- Study start8 Aug 2011
- Study completion17 Apr 2013
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.
- 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
- Observational
- Time perspective
- Prospective
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Human Genome Research Institute (NHGRI)
- Sponsor type
- US National Institutes of Health
- Investigators
- Peter J McGuire, M.D., Principal investigator, National Human Genome Research Institute (NHGRI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01421888
- Sponsor's protocol ID
- 110217
- Other IDs
- 11-HG-0217
- Status last verified
- 17 Apr 2013
- First submitted
- 20 Aug 2011
- Last updated
- 9 Dec 2019
- Results posted
- No
Publications
Barshop BA, Summar ML. Attitudes regarding vaccination among practitioners of clinical biochemical genetics. Mol Genet Metab. 2008 Sep-Oct;95(1-2):1-2. doi: 10.1016/j.ymgme.2008.08.001. No abstract available.
PubMed 18816884Batshaw ML, Brusilow S, Waber L, Blom W, Brubakk AM, Burton BK, Cann HM, Kerr D, Mamunes P, Matalon R, Myerberg D, Schafer IA. Treatment of inborn errors of urea synthesis: activation of alternative pathways of waste nitrogen synthesis and excretion. N Engl J Med. 1982 Jun 10;306(23):1387-92. doi: 10.1056/NEJM198206103062303.
PubMed 7078580Summar M, Tuchman M. Proceedings of a consensus conference for the management of patients with urea cycle disorders. J Pediatr. 2001 Jan;138(1 Suppl):S6-10. doi: 10.1067/mpd.2001.111831.
PubMed 11148544
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The NIH UNI Study: Urea Cycle Disorders, Nutrition and Immunity
- ClinicalTrials.gov ID
- NCT01421888
- Acronym / sponsor ID
- 110217
- Conditions
- Argininosuccinic Aciduria, Carbamoyl-Phosphate Synthase I Deficiency, Citrullinemia, Ornithine Carbamoyltransferase Deficiency, Hyperargininemia, N-Acetylglutamate Synthase Deficiency
- Keywords
- Immunity, Urea Cycle Disorder, Nutrition, Vaccination, Influenza
- Study type
- Observational
- Recruitment status
- Terminated
- Enrolment
- 4 participants (actual)
- Lead sponsor
- National Human Genome Research Institute (NHGRI)US National Institutes of Health
- Study start
- 8 Aug 2011
- Study completion
- 17 Apr 2013
- First posted
- 23 Aug 2011 (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.
Objectives:
- To study nutrition and immune system problems in people with urea cycle disorders.
- To study how people with urea cycle disorders and healthy volunteers respond to standard flu and/or hepatitis A vaccines.
- To compare differences in nutrition and immune systems of people with urea cycle disorders with that of healthy volunteers.
Eligibility:
- Healthy males and females at least 2 years of age who are able to travel to the National Institutes of Health hospital in Bethesda, MD
- Males and females at least 2 years of age who have a urea cycle disorder and are able to travel to the National Institutes of Health hospital in Bethesda, MD.
Design:
For Patients with urea cycle disorder:
- Participants will spend 2 to 3 days in the National Institutes of Health hospital for the following tests:
- A physical exam and review of medical history
- Food log for 3 days before the start of the study
- Blood tests
- 24-hour urine collection
- Resting metabolism test
- DEXA scan imaging study of bones and body fat
- Participants who are old enough to do certain tasks by themselves (like dressing and eating) can choose to have the following extra tests:
- 24-hour metabolic room measurements
- BodPod(Registered Trademark) study to measure bones and body fat
- Participants may choose to have a flu shot and/ or Hepatitis A shot at the end of the study and will be monitored to check for possible side effects.
- Participants will return within 1 to 3 months for follow-up tests/immunizations.
For Healthy Volunteers:
- Participants will be seen at the outpatient clinics at the National Institutes of Health hospital for up to 2 visits for the following:
- Review food log completed 3 days before the start of the study
- Blood tests
- Participants may choose to have a flu shot and/ or Hepatitis A shot at the end of the study and will be monitored to check for possible side effects.
- Participants will return within 1 to 3 months for follow-up tests/immunizations.
- Review of second food log completed 3 days before second outpatient visit
Detailed description
Urea cycle disorders (UCD) are amongst the most frequent of the inborn errors of metabolism (IEM) and result from a block in the hepatic disposal of waste nitrogen from protein catabolism. Viral infections play a significant role in precipitating life-threatening acute hyperammonemic crises in UCD. The recent H1N1 influenza pandemic has placed this vulnerable population at significant risk. The standard of care for these patients is routine vaccination for seasonal and H1N1 influenza viruses. However, nutritional deficiencies and their underlying enzymopathy may affect the efficacy of vaccination.
Dietary management of urea cycle disorders includes dietary modification with protein restriction. Protein energy malnutrition, essential fatty acid deficiencies and micronutrient deficiencies due to restrictive dietary management have been reported in various inborn errors of metabolism. In general, dietary deficiencies and their effect on immune function are well documented.
In addition to the disposal of waste nitrogen, the urea cycle also generates arginine for various biologic functions. Depending on the site of the metabolic block, UCD patients are at risk for becoming systemically deficient in citrulline and arginine, with potential implications for the immune system. The immunomodulatory roles of the amino acids citrulline and arginine have been characterized in the context of nutritional deficiencies in disease states such as cancer and sepsis. Systemic infection may also deplete systemic citrulline and arginine, compounding an underlying deficiency in UCD. Cells of the immune system have a more direct relationship with the urea cycle: urea cycle enzymes arginosuccinate synthetase (ASS), arginosuccinate lyase (ASL) and arginase (ARG1) may also be components of leukocyte metabolism. Overall, general and specific nutritional deficiencies and enzymopathies affecting leukocyte metabolism may potentially affect vaccine efficacy. However, immune system function in experiments of nature such as UCD remains an understudied area.
In this protocol, we will clinically evaluate the nutritional/metabolic and immunologic states of patients with UCD or related disorders. Routine inpatient admissions will last 2-3 days and involve urine collection, blood drawing, radiological procedures, nutrition assessment and biometrics, and vaccination for combined seasonal/H1N1 influenza. Follow-up outpatient appointments will be scheduled at the end of the study period.
The study objectives will be to describe the nutritional and immune deficiencies seen, query for nutrition/enzymatic/immunologic correlations in this patient population, describe vaccine efficacy in this patient population, and search for new genes in rare families that have evidence for an unknown class of UCD. The population will consist of patients previously evaluated at NIH, physician referrals, and families directed to the study from clinicaltrials.gov as well as the National Urea Cycle Disorders Foundation. All patients will be evaluated at the NIH Clinical Center.
Study design
- Time perspective
- Prospective
Who may qualify
- Ages
- 2 to 99 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Any gender and ethnicity age 2 years and older with a diagnosis of a urea cycle disorder are eligible to enroll in this protocol.
- Patients need to be medically and nutritionally managed by a local metabolic provider. If necessary, we will obtain written consent from the patient to review medical records from their home physician to confirm eligibility.
- Any gender and ethnicity age 2 years and older are eligible to enroll in this protocol.
- Have access to own personal medical provider <TAB>
Key exclusion criteria (7 listed)
- Less than 2 years of age
- Inability to travel to NIH because of their medical condition
- Recent (6 month) history of vaccination or immune modulating drug
- Severe reactions to eggs and or latex
- History of severe reactions to previous immunizations (e.g. hives, rash, difficulty breathing)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2019.
- Background: PubMed 18816884Barshop BA, Summar ML. Attitudes regarding vaccination among practitioners of clinical biochemical genetics. Mol Genet Metab. 2008 Sep-Oct;95(1-2):1-2. doi: 10.1016/j.ymgme.2008.08.001. No abstract available.
- Background: PubMed 7078580Batshaw ML, Brusilow S, Waber L, Blom W, Brubakk AM, Burton BK, Cann HM, Kerr D, Mamunes P, Matalon R, Myerberg D, Schafer IA. Treatment of inborn errors of urea synthesis: activation of alternative pathways of waste nitrogen synthesis and excretion. N Engl J Med. 1982 Jun 10;306(23):1387-92. doi: 10.1056/NEJM198206103062303.
- Background: PubMed 11148544Summar M, Tuchman M. Proceedings of a consensus conference for the management of patients with urea cycle disorders. J Pediatr. 2001 Jan;138(1 Suppl):S6-10. doi: 10.1067/mpd.2001.111831.
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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.
Peter J McGuire, M.D. principal investigator
National Human Genome Research Institute (NHGRI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Argininosuccinic Aciduria and Carbamoyl-Phosphate Synthase I Deficiency, run by National Human Genome Research Institute (NHGRI) 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 6 inclusion and 7 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: stopped early, as of the sponsor's last update on 9 Dec 2019. 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. 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 was stopped early. Results are not available in the source record.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01421888, 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 9 Dec 2019.