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Sickle Cell DiseaseNCT01950429

Evaluation of Sickle Cell Liver Disease

An observational study of Sickle Cell Disease, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 99 years
Conditions the study is for
Sickle Cell Disease
How many people
42 participants
Where
1 siteUnited States
Study dates
16 Oct 2013to 11 Jun 2019
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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.

Who may be able to join

  • 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)

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

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.
Read more

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.
Read the 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 12-24 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.

Keywords
Microbiome, Sickle Cell Disease, Bone Marrow Transplant, Natural History
Medical subject headings
Anemia, Sickle Cell

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 5 years

Secondary outcomes (1)

  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.

    Measured: 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Sep 2013 (estimated)
  2. Study start16 Oct 2013
  3. Primary completion11 Jun 2019
  4. Study completion11 Jun 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
42 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01950429
Sponsor's protocol ID
130196
Other IDs
13-DK-0196
Status last verified
May 2022
First submitted
21 Sep 2013
Last updated
16 May 2022
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: .All collected IPD.

Publications

  • 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.

    PubMed 17459050

  • 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.

    PubMed 18508803

  • 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.

    PubMed 21131035

Questions about this trial

What is this clinical trial studying?

An observational study of Sickle Cell Disease, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 May 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01950429, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2022.

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