Clinical Trial Details
— Status: Recruiting
Administrative data
NCT number |
NCT04602325 |
Other study ID # |
14021 |
Secondary ID |
R21TR003166-01 |
Status |
Recruiting |
Phase |
|
First received |
|
Last updated |
|
Start date |
July 9, 2020 |
Est. completion date |
May 2027 |
Study information
Verified date |
February 2024 |
Source |
Children's National Research Institute |
Contact |
Katie Rice, MPH, CCRP |
Phone |
202-476-6191 |
Email |
krice3[@]childrensnational.org |
Is FDA regulated |
No |
Health authority |
|
Study type |
Observational
|
Clinical Trial Summary
Ammonia is a waste product of protein and amino acid catabolism and is also a potent
neurotoxin. High blood ammonia levels on the brain can manifest as cytotoxic brain edema and
vascular compromise leading to intellectual and developmental disabilities. The following
aims are proposed:
Aim 1 of this study will be to determine the chronology of biomarkers of brain injury in
response to a hyperammonemic (HA) brain insult in patients with an inherited hyperammonemic
disorder.
Aim 2 will be to determine if S100B, NSE, and UCHL1 are altered in patients with two other
inborn errors of metabolism, Maple Syrup Urine Disease (MSUD) and Glutaric Acidemia (GA1).
Description:
Ammonia is a waste product of protein and amino acid catabolism and is also a potent
neurotoxin. The onslaught of high blood ammonia levels on the brain can manifest as cytotoxic
brain edema and vascular compromise leading to intellectual and developmental disabilities.
In addition, clinical hyperammonemia recurs at varying intervals, which can increase the
cumulative damage to the brain and the chance of irreversible coma and death during a
hyperammonemia episode due to vascular compromise or brain herniation. The threshold of
tolerance for elevated blood ammonia is very low and concentrations above 100 µM can cause
brain dysfunction manifested as nausea, vomiting, lethargy, and abnormal behavior; higher
concentrations can cause coma and even death. Failure to remove ammonia can be due to
inherited defects of the urea cycle, some defects in amino acid catabolism, and degradation
of fatty acids.
Aim 1 - To determine the chronology of biomarkers of brain injury - S100B, NSE, and UCHL1 -
in response to a hyperammonemic (HA) brain insult in patients with an inherited
hyperammonemic disorder. We hypothesized that elevations of S100B, NSE, and UCHL1 will
parallel the rise in blood ammonia. These biomarkers will be measured concurrently to ammonia
levels throughout hospitalizations for HA until normalization of patient's blood ammonia and
mental status.
Aim 2 - To determine if S100B, NSE, and UCHL1 are altered in patients with two other inborn
errors of metabolism in which the primary pathology is neurological injury, Maple Syrup Urine
Disease (MSUD) and Glutaric Acidemia (GA1). We hypothesize that neuronal and astroglial
injury in these disorders may also result in increased levels of S100B, NSE, and UCHL1.
Metabolic patients will be enrolled either during a hospitalization or in outpatient clinic,
but outpatient enrollment is preferred. Metabolic patients typically have multiple laboratory
tests performed at their outpatient visits. We will obtain the discarded blood samples from
such laboratory tests in order to measure S100B, NSE, and UCHL1 levels at baseline (normal
blood ammonia), which will provide data on biomarker levels following recovery from a
hyperammonemic episode.
During hospitalization for metabolic decompensation or for hypoxic-ischemic encephalopathy,
sequential measurements of S100B, NSE and UCHL1 levels will be obtained from discarded blood
samples. We will obtain S100B, NSE, and UCHL1 levels from collected discarded blood samples
at all subjects' next outpatient visit following their hospitalization, to determine if
levels return to baseline.