Evaluation of Sickle Cell Liver Disease

NCT01950429 | Completed

• 2 other identifiers: 13019613-DK-0196
• Study Type: observational
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

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 24 months later.
• Over the 2-year study period, participants will have blood drawn 2-4 times and stool samples collected 2 times.

Conditions

Sickle Cell Disease

Keywords

Microbiome; Sickle Cell Disease; Bone Marrow Transplant; Natural History

Outcome Measures

Primary Outcomes (1)

• 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

  To assess severity, rule out portal hypertension, judge prognosis and to help in decisions on altering management

  5 years

Secondary Outcomes (1)

• 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.

  5 years

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Sickle cell disease (SCD) causes multi-organ dysfunction and early death in affected individuals (1-4). 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 (5). It is therefore imperative to identify patients with liver dysfunction and damage for possible early intervention.

You may qualify if:

• 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)

You may not qualify if:

• If not taking measures to prevent pregnancy during the period of study
• Incapacity to provide informed consent

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Panepinto JA, Walters MC, Carreras J, Marsh J, Bredeson CN, Gale RP, Hale GA, Horan J, Hows JM, Klein JP, Pasquini R, Roberts I, Sullivan K, Eapen M, Ferster A; Non-Malignant Marrow Disorders Working Committee, Center for International Blood and Marrow Transplant Research. Matched-related donor transplantation for sickle cell disease: report from the Center for International Blood and Transplant Research. Br J Haematol. 2007 Jun;137(5):479-85. doi: 10.1111/j.1365-2141.2007.06592.x. Epub 2007 Apr 24.

  PMID: 17459050 BACKGROUND

• Berthaut I, Guignedoux G, Kirsch-Noir F, de Larouziere V, Ravel C, Bachir D, Galacteros F, Ancel PY, Kunstmann JM, Levy L, Jouannet P, Girot R, Mandelbaum J. Influence of sickle cell disease and treatment with hydroxyurea on sperm parameters and fertility of human males. Haematologica. 2008 Jul;93(7):988-93. doi: 10.3324/haematol.11515. Epub 2008 May 27.

  PMID: 18508803 BACKGROUND

• Rees DC, Williams TN, Gladwin MT. Sickle-cell disease. Lancet. 2010 Dec 11;376(9757):2018-31. doi: 10.1016/S0140-6736(10)61029-X. Epub 2010 Dec 3.

  PMID: 21131035 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Anemia, Sickle Cell

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Theo Heller, M.D.

  National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2013
• First Posted: September 25, 2013
• Study Start: October 16, 2013
• Primary Completion: June 11, 2019
• Study Completion: June 11, 2019
• Last Updated: May 16, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, 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.

Locations

US (1)