Clinical Trial Details
— Status: Active, not recruiting
Administrative data
NCT number |
NCT05582447 |
Other study ID # |
2018-0310 |
Secondary ID |
|
Status |
Active, not recruiting |
Phase |
|
First received |
|
Last updated |
|
Start date |
April 17, 2018 |
Est. completion date |
December 31, 2026 |
Study information
Verified date |
January 2024 |
Source |
Children's Hospital Medical Center, Cincinnati |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Observational
|
Clinical Trial Summary
Objective:
The investigators propose to perform ektacytometry on 20 pediatric patients over age one with
cholestatic liver diseases and a direct bilirubin level of greater than 2 gm/dl. The most
common diagnoses will be extrahepatic biliary atresia, progressive familial intrahepatic
cholestasis, Alagille syndrome, autoimmune hepatitis, primary sclerosing cholangitis, and
parenteral nutrition-associated cholestasis. The investigators will correlate the osmotic
fragility and deformability with direct bilirubin levels, serum cholesterol levels, serum
bile acid levels, and vitamin E levels.
Design/Methods:
This pilot study will be a single center, prospective cross-sectional investigation of red
blood cell ektacytometry in pediatric patients with extrahepatic cholestasis who are followed
at Cincinnati Children's Hospital Medical Center. The study will include all participants
with cholestasis regardless of the etiology in order to maximize the number of participants.
While the population will be heterogeneous, the investigators will stratify participants
according to diagnosis, recognizing that only a few participants may fall into each
diagnostic category. Ektacytometry will be the method utilized to measure osmotic fragility
and deformability of the RBC membrane. The ektacytometry of red cells from cholestatic
patients will be compared to that of red cells obtained from contemporaneous age-matched
controls recruited among patients without liver disease or red cell membrane defects
undergoing blood sampling for evaluation of other entities including but not confined to
functional abdominal pain.
Description:
Primary Aim:
The primary aim is to determine if ektacytometry of red blood cells is abnormal in a
population of pediatric patients over age one with cholestasis.
Secondary Aims:
The secondary aim is to ascertain the extent at which abnormalities in bilirubin levels, bile
acid levels, vitamin E levels or cholesterol levels in cholestatic patients are related to
changes in red blood cell ektacytometry in this patient population.
BACKGROUND Cholestatic liver disease is an umbrella term for reduced bile flow from either
extrahepatic obstruction of bile ducts or faulty hepatocyte bile secretion. Cholestasis is a
well-recognized cause of dyslipidemia, and are closely associated with abnormal cholesterol
and phospholipid metabolism (3). Cholesterol conversion to bile acids may be impaired, and
apo-lipoprotein B binding to cholesterol may be impaired, resulting in the formation of
lipoprotein X which contains apo-lipoprotein C (3). The end result of dyslipidemia in
cholestatic patients is hypercholesterolemia and an increased membrane cholesterol to
phospholipid ratio (3).
The lack of bile entering the digestive tract can lead to increased serum cholesterol, and
abnormally high red cell membrane cholesterol: phospholipid ratios, resulting in altered red
cell membrane structural integrity (4,5). To test for this phenomenon in patients with
extrahepatic biliary atresia, 20 pediatric patients will be tested using ektacytometry to
test the deformability and osmotic fragility of red blood cells.
Ektacytometry is a diagnostic tool used to measure the deformability of red blood cells on an
osmotic gradient (6). More specifically it measures deformability due to shear stress, while
the RBC are suspended in an osmotic medium (6,7). It can differentiate among several blood
maladies such as hereditary spherocytosis, hereditary elliptocytosis, Southeast Asian
ovalocytosis, and pyropoikilocytosis that are otherwise difficult to diagnose (8). It does
this by analyzing rheological behavior under constant shear stress in vitro and using
photometric analysis of deformability. This is then quantified and provides a specific
ektacytometry curve (Figure 1).
The ektacytometry curve will have several unique features depending on the red blood cell
being analyzed. The Omin portion of the curve represents the value of the osmolality in which
50 percent of the red blood cells lyse. The Elmax is the value of the elongation index that
reaches its maximum near physiologic osmolality (300 mOsm/Kg). And lastly the Ohyp, which
represents the declining portion of the curve and correlates to the initial intracellular
viscosity of the cell sample.
To date, ektacytometry has not been employed systematically to characterize potential red
cell abnormalities in cholestatic patients. In our analysis the ektacytometry profiles of
cholestatic patients will be compared to those of historical non-cholestatic age-matched
controls. The degree of fragility will be correlated with serum direct bilirubin levels,
serum cholesterol levels, and vitamin E levels.
STUDY DESIGN This pilot study will be a single center, prospective cross-sectional
investigation into the ektacytometry of red blood cells taken from 20 cholestatic pediatric
patients followed at Cincinnati Children's Hospital. Patients are seen regularly for
continued follow up in the hepatology clinic. Parents of all of these patients will be asked
to participate in this investigation. The investigators will also contemporaneously analyze
ektacytometry of 20 age-matched controls recruited from the general GI clinics with neither
cholestatic liver disease nor know red cell membrane defects.
DURATION The study is anticipated to take approximately 6-12 months to complete. This time
table includes 3-6 months to recruit patients and perform the assays and another 3-6 months
to analyze the data and complete a manuscript.