Evaluation of Sickle Cell Liver Disease
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01950429|
Recruitment Status : Completed
First Posted : September 25, 2013
Last Update Posted : May 16, 2022
- Study Details
- Tabular View
- No Results Posted
- How to Read a Study Record
- 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.
- To explore specific factors that improve or worsen sickle cell liver disease after a stem cell transplant.
- Adults ages 18 and older with sickle cell liver disease.
- 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 24 months later.
- Over the 2-year study period, participants will have blood drawn 2-4 times and stool samples collected 2 times.
|Condition or disease|
|Sickle Cell Disease|
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 12-24 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.
|Study Type :||Observational|
|Actual Enrollment :||42 participants|
|Official Title:||Evaluation of Sickle Cell Liver Disease|
|Actual Study Start Date :||October 16, 2013|
|Actual Primary Completion Date :||June 11, 2019|
|Actual Study Completion Date :||June 11, 2019|
- Histological evidence of regression of liver disease in stem cell transplanted sickle cell patients measured by degree of improvement in Deugnier's and HAI score [ Time Frame: 5 years ]To assess severity, rule out portal hypertension, judge prognosis and to help in decisions on altering management
- 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: 5 years ]
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, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years to 99 Years (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
|Sampling Method:||Non-Probability Sample|
- All age greater than 18 able to consent, male or female
- Capacity to provide written informed consent
- All ethnicities
- Sickle cell genotypes; Homozygous Hemoglobin S Disease, Heterozygous Hemoglobin SC and S beta thalassemia including SB+ and SB0
- 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)
- If not taking measures to prevent pregnancy during the period of study
- Incapacity to provide informed consent
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01950429
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Theo Heller, M.D.||National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)|
|Responsible Party:||National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)|
|Other Study ID Numbers:||
|First Posted:||September 25, 2013 Key Record Dates|
|Last Update Posted:||May 16, 2022|
|Last Verified:||May 2022|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||Yes|
|Plan Description:||.All collected IPD.|
Informed Consent Form (ICF)
|Time Frame:||IPD and any additional supporting information will become available 6 months after publication.|
|Access Criteria:||Any secondary use requests will be reviewed and approved by the PI Theo Heller, MD.|
|Studies a U.S. FDA-regulated Drug Product:||No|
|Studies a U.S. FDA-regulated Device Product:||No|
Sickle Cell Disease
Bone Marrow Transplant
Anemia, Sickle Cell
Digestive System Diseases
Anemia, Hemolytic, Congenital
Genetic Diseases, Inborn