Liver Fibrosis in Sickle Cell Disease

• ClinicalTrials.gov Identifier: NCT02007746
• Recruitment Status: Completed
• First Posted: December 11, 2013
• Last Update Posted: May 26, 2021
• Sponsor: University of Miami
• Information provided by (Responsible Party): Ofelia Alvarez, University of Miami

Tracking Information

• First Submitted Date: December 6, 2013
• First Posted Date: December 11, 2013
• Last Update Posted Date: May 26, 2021
• Actual Study Start Date: July 2012
• Actual Primary Completion Date: June 1, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 6, 2013)

Liver transient elastography (FibroScan) of liver iron content and stiffness [ Time Frame: at imaging visit (3 minutes) ]

Liver transient elastography (FibroScan) uses a probe consisting of an ultrasound transducer located at the end of a vibrating piston. The piston produces a vibration of low amplitude and frequency, which generate a shear wave that passes through the skin and liver tissue. The ultrasound then detects the propagation of the shear wave through the liver (at a depth of 25 - 65 mm below the skin surface) by measuring its velocity. The shear wave velocity is directly related to the tissue stiffness, with a higher velocity equating to higher tissue stiffness, corresponding to increasing severity of fibrosis.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 6, 2013)

• magnetic resonance imaging (MRI) measure of liver iron content and stiffness [ Time Frame: at imaging visit (about 30-60 minutes) ]
• liver function tests (ALT, AST, serum alkaline phosphate, GGTP, total bilirubin, direct bilirubin), complete blood count, platelets, reticulocyte count, serum ferritin to assess liver function and evaluate overall health [ Time Frame: at clinic visit blood draw (about 1 minute) ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Liver Fibrosis in Sickle Cell Disease
• Official Title: Assessment of Liver Fibrosis in Patients With Sickle Cell Disease
• Brief Summary: Patients with sickle cell disease many have a number of systemic complications, including liver problems. Some of these liver problems lead to liver fibrosis/cirrhosis, secondary to chronic blood transfusions. The purpose of this study is to investigate FibroScan readings in patients with sickle cell disease and iron overload secondary to blood transfusions, and to correlate the FibroScan results with Ferriscan. A comparison with the results of FibroScan to patients with Sickle cell without known liver disease, who have never been on chronic transfusions and with normal liver function profiles will also be made.The primary hypothesis is that the results of FibroScan will correlate with the results of Ferriscan and liver biopsy.

Detailed Description

Liver biopsy is the gold standard to examine the liver for iron deposits and histology. However, liver biopsy is invasive and involves a risk of bleeding and pain. Biopsy may also miss significant pathology if the small biopsy specimen is taken from an uninvolved part of the liver. Non-invasive techniques such as MRI are now used to evaluate the liver iron content. MRI can visualize the whole liver and measure liver iron content. MRI, however, will not detect liver scarring.

Liver transient elastography (FibroScan) is a non-invasive ultrasound tool for assessing liver fibrosis or scarring by measuring liver stiffness (LSM). Compared with liver biopsy, FibroScan provides immediate results and is a painless, short (3 mins), simple procedure to perform. In some studies FibroScan reports have correlated well with liver biopsy results of fibrosis and cirrhosis, and with Ferriscan, ferritin and liver function tests.

This purpose of this study is to investigate the role of FibroScan in individuals with sickle cell anemia and iron overload or who have a diagnosis of liver disease, and to compare FibroScan readings with magnetic resonance imaging.

We will also compare the results of the Fibroscan with liver biopsy.

This study will also compare the results of FibroScan to patients with Sickle cell without any known liver disease, who have never been on chronic transfusions (defined as no more than 4 transfusions in lifetime) and who have normal liver function profiles.

• Study Type: Observational
• Study Design: Observational Model: Case-Control; Time Perspective: Cross-Sectional
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: 30 subjects with sickle cell disease and iron overload. 30 control subjects without history of chronic transfusions (less than 4 transfusions in lifetime) and without evidence of liver pathology.
• Condition: Sickle Cell Disease

Intervention

• Other: Liver transient elastography (Fibroscan)
  Fibroscan will be performed as a measure of liver stiffness. The study will be obtained free of charge in this study.
  Other Name: FibroScan
• Other: Ferriscan
  Ferriscan will be done to assess the quantity of liver iron in iron overloaded subjects.
• Procedure: Liver biopsy in iron overloaded subjects.
  Liver biopsy will be done and the results will be compared to Fibroscan results.

Study Groups/Cohorts

• Subjects with sickle cell disease and iron overload
  Patients will have blood tests done to evaluate liver function and general health, then have FibroScan and Ferriscan. A blinded (no access to laboratory parameters or available data) radiologist will interpret the Ferriscan. Liver biopsy will be also obtained (if not done within the previous year). Otherwise, the results of the recent liver biopsy will be collected.
  Interventions:

  • Other: Liver transient elastography (Fibroscan)
  • Other: Ferriscan
  • Procedure: Liver biopsy in iron overloaded subjects.
• control patients with sickle cell disease
  Patients 10 years and older with sickle cell disease without history of chronic transfusions (less than 4 transfusions in a lifetime) and without obvious liver disease. Will have liver function blood tests and general health check ups. Then will have FibroScan performed. No liver biopsy will be performed in control patients.
  Intervention: Other: Liver transient elastography (Fibroscan)

Publications *

• Voskaridou E, Plata E, Douskou M, Papadakis M, Delaki EE, Christoulas D, Terpos E. Treatment with deferasirox (Exjade) effectively decreases iron burden in patients with thalassaemia intermedia: results of a pilot study. Br J Haematol. 2010 Jan;148(2):332-4. doi: 10.1111/j.1365-2141.2009.07930.x. Epub 2009 Oct 26. No abstract available.
• Fraquelli M, Cassinerio E, Roghi A, Rigamonti C, Casazza G, Colombo M, Massironi S, Conte D, Cappellini MD. Transient elastography in the assessment of liver fibrosis in adult thalassemia patients. Am J Hematol. 2010 Aug;85(8):564-8. doi: 10.1002/ajh.21752.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 21, 2021): 26
• Original Estimated Enrollment (submitted: December 6, 2013): 30
• Actual Study Completion Date: June 1, 2017
• Actual Primary Completion Date: June 1, 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• pediatric patients age 10 years and older with sickle cell disease

• meeting other criteria:

  1. history of chronic transfusion and iron overload and/or
  2. known liver disease related to sickle cell or iron overload
• signed consent and assent (as applicable)

Exclusion Criteria:

• children younger than 10 years
• Pregnant females
• Prisoners
• Other causes of liver disease, unrelated to sickle cell or iron overload

Inclusion criteria for controls:

• Patients 10 years and older with sickle cell disease without history of chronic transfusions (less than 4 transfusions in a lifetime)
• and without obvious liver disease.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 10 Years to 65 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02007746
• Other Study ID Numbers: 20120222
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Ofelia Alvarez, University of Miami
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Miami
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Ofelia Alvarez, MD; University of Miami - Director Sickle Cell Services Pediatric Hematology/Oncology

• PRS Account: University of Miami
• Verification Date: May 2021