The NIH UNI Study: Urea Cycle Disorders, Nutrition and Immunity
| Status: | Terminated |
|---|---|
| Conditions: | Other Indications, Hematology, Metabolic |
| Therapuetic Areas: | Hematology, Pharmacology / Toxicology, Other |
| Healthy: | No |
| Age Range: | 2 - 99 |
| Updated: | 4/6/2019 |
| Start Date: | August 8, 2011 |
| End Date: | April 17, 2013 |
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
- 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
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.
(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.
- INCLUSION CRITERIA:
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
EXCLUSION CRITERIA:
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
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
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