Clinical trial NCT02067130: Utility of Fibroscan in Estimating Hepatic Iron Concentration
Official title: Utility of Transient Elastography (Fibroscan) in Estimating Hepatic Iron Concentration in Comparison to MRI in Patients With Transfusion Dependent Hemoglobinopathies
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Hereditary Anemias
Keywords: Beta Thalassemia Major
Lead sponsor: University of British Columbia
Sponsor class: OTHER
First posted: 2014-02-20
Enrollment: 30
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: In patients with hereditary anemias (e.g. thalassemias), defective red blood cells are produced due to an error in the genes, or DNA, that provide the instructions for their synthesis. As a result, hereditary anemias are characterized by chronically low hemoglobin, which is contained inside red blood cells and carries oxygen throughout the body. In more severe cases, patients are dependent on frequent blood transfusions to replenish the hemoglobin.

The body has limited ability to get rid of excess iron. However, with repeated blood transfusions, the iron level in the body builds up because the red blood cells contain iron as heme. Over time, the high level of iron accumulates in organs such as the heart, liver, and pancreas causing heart problems, liver failure, and diabetes. As a result, patients who receive multiple blood transfusions need to be monitored for iron overload, and be started on medical therapy in a timely fashion to prevent organ damage.

Liver is usually the first and the most affected organ by iron accumulation, so knowledge of its iron concentration provides estimate of total body iron load. Liver biopsy is the gold standard in measuring the iron concentration in the liver, but it is invasive and cannot be performed on routine basis. MRI is another option that can assess liver iron concentration non-invasively, and is currently recommended for monitoring iron load on a yearly basis. However, MRI has a high cost and is not easily accessible in Canada. The investigators aim to determine if transient elastography (Fibroscan), which is a form of ultrasound that measures liver stiffness, can accurately assess liver iron concentration.

Hypothesis:

Fibroscan reading correlates with MRI and serum ferritin in estimating hepatic iron concentration.

Detailed description: Inclusion criteria: All adult patients (age 19 or greater) with hereditary anemias requiring chronic blood transfusion at St. Paul's Hospital will be invited to participate in this study. The majority of patients will be β-Thalassemia Major. They will be given a pamphlet containing the details of the study and can contact the research assistant or clinic nurse for more information should they be interested.

Exclusion criteria: Patients with known Hepatitis B positive, known Hepatitis C positive, known HIV positive, known liver cirrhosis, known primary liver disease such as Wilson's disease and hereditary hemochromatosis are excluded from the study.

Written consent will be obtained from all participants by the clinic nurse/research assistant prior to enrollment.

Study procedures:

Data to be collected retrospectively from patient charts (St. Paul's Hospital's EMR/Sunrise Clinical Manager and paper chart) include: baseline demographic data (age, gender, hematological condition), medical comorbidities and complications related to iron overload (Diabetes, hypothyroidism, cardiomyopathy/arrhythmia and congestive heart failure, hypogonadotropic hypogonadism, osteopenia and osteoporosis syndrome..etc), current medications including use of iron chelators such as desferrioxamine, deferasirox, deferiprone or combination therapy, viral hepatitis status (B and C) and date of test, liver cirrhosis status (stage), liver biopsy result (iron concentration) and date of procedure. Patients with chronic transfusion requirement usually undergo annual MRI at the beginning of the year to estimate hepatic iron concentration as per standard practice. This year (2013), R2 MRI (FerriScan) will also be available for the first time to all patients in BC as part of routine monitoring for iron overload. Details/results from both techniques (i.e. same images collected in one scan, but analyzed differently using R2 and T2\* algorithms) will be collected.

Eligibility criteria: Inclusion Criteria:

* All adult patients (age 19 or greater) with hereditary anemias requiring chronic blood transfusion at St. Paul's Hospital will be invited to participate in this study. The majority of patients will be β-Thalassemia Major.

Exclusion Criteria:

* Known Hepatitis B positive
* Known Hepatitis C positive
* Known HIV positive
* Known liver cirrhosis
* Known primary liver disease such as Wilson's disease and hereditary hemochromatosis

Primary outcomes:
measure: Fibroscan reading collected at the Gastroenterologist's outpatient clinic
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
Study officials:
affiliation: Department of Medicine, Division of Hematology St. Paul's Hospital, University of British Columbia
name: Hatoon Ezzat, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Medicine, Division of Gastroenterology, St. Paul's Hospital, University of British Columbia
name: Hinhin Ko, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Jung KS, Kim SU. Clinical applications of transient elastography. Clin Mol Hepatol. 2012 Jun;18(2):163-73. doi: 10.3350/cmh.2012.18.2.163. Epub 2012 Jun 26.
citation: Loustaud-Ratti VR, Cypierre A, Rousseau A, Yagoubi F, Abraham J, Fauchais AL, Carrier P, Lefebvre A, Bordessoule D, Vidal E, Sautereau D, Jaccard A. Non-invasive detection of hepatic amyloidosis: FibroScan, a new tool. Amyloid. 2011 Mar;18(1):19-24. doi: 10.3109/13506129.2010.543443. Epub 2011 Jan 10.
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citation: Gandon Y, Olivie D, Guyader D, Aube C, Oberti F, Sebille V, Deugnier Y. Non-invasive assessment of hepatic iron stores by MRI. Lancet. 2004 Jan 31;363(9406):357-62. doi: 10.1016/S0140-6736(04)15436-6.
citation: Hou P, Popat UR, Lindsay RJ, Jackson EF, Choi H. A practical approach for a wide range of liver iron quantitation using a magnetic resonance imaging technique. Radiol Res Pract. 2012;2012:207391. doi: 10.1155/2012/207391. Epub 2012 Dec 11.
citation: Argyropoulou MI, Astrakas L. MRI evaluation of tissue iron burden in patients with beta-thalassaemia major. Pediatr Radiol. 2007 Dec;37(12):1191-200; quiz 1308-9. doi: 10.1007/s00247-007-0567-1. Epub 2007 Aug 21.