Evaluation of Sickle Cell Liver Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) )
ClinicalTrials.gov Identifier:
NCT01950429
First received: September 21, 2013
Last updated: October 2, 2014
Last verified: June 2014
  Purpose

Background:

- Sickle cell disease changes the shape of red cells. This makes them more likely to break down as they get stuck in small blood vessels. This leads to low red cell count and also damage to small blood vessels that supply many organs. One of the affected organs is the liver. Sickle cell disease and its treatment through blood transfusion can lead to significant liver damage. This disease also can cause the liver to regrow abnormally after damage. This can cause high blood pressure in the liver. Researchers want to know if curing sickle cell disease with a stem cell transplant improves liver damage.

Objectives:

- To explore specific factors that improve or worsen sickle cell liver disease after a stem cell transplant.

Eligibility:

- Adults ages 18 and older with sickle cell liver disease.

Design:

  • Participation will take approximately 7 days over 2 years.
  • Visit 1: participants will be screened with medical history and review of current treatment regimen.
  • Visit 2: participants will return to the clinic for explanation of the study and physical exam. They will also have blood and urine tests, and scans of the liver.
  • All participants will have a 2-night stay at the clinic. They will have a liver biopsy and a test of liver pressure. They will be sedated and a tube will be inserted in a vein in their neck.
  • Participants who have a stem cell transplant will have a second biopsy about 18 months later.
  • Over the 2-year study period, participants will have blood drawn 2 4 times and stool samples collected 2 times.

Condition
Sickle Cell Disease

Study Type: Observational
Official Title: Evaluation of Sickle Cell Liver Disease

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Histological evidence of regression of liver disease in stem cell transplanted sickle cell patients measured by degree of improvement in Deugniers and HAI score. [ Time Frame: 1 year post transplant ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Clinical evidence of regression of liver disease in transplanted sickle cell patients. Evaluate relationship between change in liver disease, bile acids, microbiome and prevalence of infection in SCD. [ Time Frame: 12-18 months post transplant ] [ Designated as safety issue: No ]
  • Effect of transplantation on causes and markers of liver related mortality in SCD patientsHistological improvement in liver fibrosis score post stem cell transplant [ Time Frame: 12-18 months post transplant ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: August 2013
Estimated Study Completion Date: May 2018
Estimated Primary Completion Date: May 2018 (Final data collection date for primary outcome measure)
Detailed Description:

Sickle cell disease (SCD) causes multi-organ dysfunction and early death in affected individuals. Many succumb to complications of chronic organ dysfunction and eventual organ failure one of which is the liver.

Spectrum of sickle cell liver disease ranges from hepatic sequestration crisis, intrahepatic cholestasis, gallstones, non-cirrhotic portal hypertension, chronic sickle hepatopathy and cirrhosis to complications of the treatment of the disease including secondary iron overload and viral hepatitis. Though liver transplantation has been performed for SC-induced liver failure, a crude mortality rate of 60% makes it a poor choice. It is therefore imperative to identify patients with liver dysfunction and damage for possible early intervention.

Stem cell transplant is currently the only cure for SCD and at the NIH SCD hepatopathy is one of the indications for transplant. It is currently not known if stem cell transplant reverses SCD liver disease hence we intend to study and compare the nature of SCD liver disease pre and post stem cell transplant and in transplant ineligible patients. All SCD patients will be screened for liver disease prior to enrollment including fibroscan evaluation. Primary end point is histological evidence of regression of liver disease. Hence all patients in the transplant eligible arm will undergo liver biopsy pre and 12-18 months post transplant. Transplant ineligible patients will be offered liver biopsy when clinically indicated. Patients that have already undergone transplant will be included and their data evaluated retrospectively. Serum and plasma, liver tissue and stool samples will be evaluated extensively for parameters such as liver function tests, iron metabolism, clotting factors, and inflammatory markers including microbial products. The intention of the study is to use sickle cell disease as a model of predicting markers of progression and regression of liver disease.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA

    1. All age greater than 18 able to consent, male or female
    2. Capacity to provide written informed consent
    3. All ethnicities
    4. Sickle cell genotypes; Homozygous Hemoglobin S Disease, Heterozygous Hemoglobin SC and S beta thalassemia including SB+ and SB0
    5. Evidence of SCD liver dysfunction by abnormal liver laboratory parameters in at least 2 of the following; alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), direct and total serum bilirubin > 1 times ULN)

EXCLUSION CRITERIA:

  1. If not taking measures to prevent pregnancy during the period of study
  2. Incapacity to provide informed consent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01950429

Contacts
Contact: Vanessa Haynes-Williams, R.N. (301) 451-7007 vhaynes@mail.nih.gov
Contact: Ohad Etzion, M.D. (301) 451-6980 ohad.etzion@nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Ohad Etzion, M.D. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) )
ClinicalTrials.gov Identifier: NCT01950429     History of Changes
Other Study ID Numbers: 130196, 13-DK-0196
Study First Received: September 21, 2013
Last Updated: October 2, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Microbiome
Sickle Cell Disease
Bone Marrow Transplant

Additional relevant MeSH terms:
Anemia, Sickle Cell
Liver Diseases
Anemia
Anemia, Hemolytic
Anemia, Hemolytic, Congenital
Digestive System Diseases
Genetic Diseases, Inborn
Hematologic Diseases
Hemoglobinopathies

ClinicalTrials.gov processed this record on October 23, 2014