Prevalence and Development of Liver Dysfunction in Hematopoietic Stem Cell Transplant

Hematopoietic Stem Cell Transplant Clinical Trial

Official title:

Prevalence and Development of Liver Dysfunction in Hematopoietic Stem Cell Transplant: A Prospective Natural History Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05722210
• Other study ID #: 10000545
• Secondary ID: 000545-DK
• Status: Not yet recruiting
• Start date: June 26, 2024
• Est. completion date: June 30, 2031

Study information

• Verified date: February 5, 2024
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Shani C Scott, R.N.
• Phone: (301) 435-6121
• Email: shani.scott[@]nih.gov
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Background:

Hematopoietic stem cell transplant (HSCT) is a common treatment for many cancers and other illnesses. But many people who have HSCT go on to develop liver dysfunction. Researchers want to know more about how and why this happens. In this natural history study, they will try to learn what factors lead to liver dysfunction; how underlying liver disease may affect the results of HSCT; and how HSCT may contribute to liver dysfunction.

Objective:

To understand the links between HSCT and liver dysfunction.

Eligibility:

Adults aged 18 years or older and children 3 to 17 years who are being evaluated for HSCT.

Design:

This study involves 11 visits in 4 years. Most visits will be in the first year.

Before and after their HSCT, participants will undergo these tests:

Physical exam, including blood tests and a test of heart function. Participants will provide stool samples.

Liver biopsies. Samples of liver tissue will be removed. This may be done either by inserting a needle through the right side of the chest, or with a thin tube threaded to the liver from a vein in the neck. Adult participants will undergo this procedure 2 times: once before the HSCT and once about a year later.

Imaging scans. Participants will lie on a bed that moves into either a cylinder or a donut-shaped machine.

Ultrasound. Participants will lie still. A probe that uses sound waves will be slid over their skin to get pictures of the liver.

Fibroscan exam. This is like an ultrasound that uses a special probe to measure the toughness of the liver.

...

Description:

Study Description:

Liver dysfunction is common in patients that have undergone hematopoietic stem cell transplant (HSCT) and is associated with increased mortality. We aim to study the natural history of liver dysfunction in HSCT, what factors contribute to the development of liver dysfunction, and how underlying liver disease affects complications and outcomes of HSCT. We hypothesize that those patients with underlying liver disease or those who develop liver disease have increased morbidity and mortality compared to those without liver disease.

Objectives:

Primary Objective:

To determine whether, at 3 months (Visit 7) after transplant, patients with liver disease at transplant are more likely to have died or have a total bilirubin >=4 mg/dL than those without liver disease at transplant.

Secondary Objectives:

To understand the impact of liver disease in HSCT on morbidity/mortality.

To understand the development and progression of liver disease in hematopoietic stem cell transplant

Tertiary Objectives:

To identify predictive/protective factors associated with presence or absence of liver disease, and severity of liver disease in patients receiving hematopoietic stem cell transplant.

Endpoints:

Primary Endpoints:

• Death or total bilirubin >=4 mg/dL at 3 months (Visit 7) after the transplant

• Mortality rate

Secondary Endpoints:

• Morbidity/cause of death

• Development of portal hypertension and sequelae (i.e., ascites, variceal bleed, thrombocytopenia, elevated portal pressure)

• Development of liver failure (i.e., coagulopathy with an International Normalized Ration (INR) 1.5, and any degree of mental alteration (encephalopathy in a subject without preexisting cirrhosis and with an illness of < 26 weeks duration, including subjects with Wilson s disease, vertically acquired HBV, or autoimmune hepatitis per AASLD guidelines 2011)

• Rate of infection (type bacterial, viral fungal, location: central line, organ infection, sepsis, etc.)

Liver dysfunction, characterized by development of the following conditions:

• Synthetic dysfunction: Total bilirubin > 4 mg/dL (20-40% in HSCT recipients or INR > 1.5

• Portal hypertension: Presence/absence of any of the following will qualify as portal hypertension- ascites, collateral vessels, elevated portal pressure

• Liver injury: ALT>4 times the upper limit of normal (22 IU/L in women, 29 IU/L in men) or Alkaline phosphatase >2.5 times the upper limit of normal

Tertiary Endpoints:

• Imaging, laboratory analysis of liver dysfunction, liver tissue pathology, medications/treatment course will be reviewed.

• Tertiary studies include stool microbiome studies, metabolomics, microbial translocation markers, flow cytometry, transcriptomics, growth factor measurement, cytokines, and chemokines measurement.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 500
• Est. completion date: June 30, 2031
• Est. primary completion date: June 30, 2031
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years and older

Eligibility

• INCLUSION CRITERIA:

An individual who meets any of the following criteria will be included in this study:

• Male and female adults >=18 years of age and children 3-17 years of age

• Undergoing evaluation for hematopoietic stem cell transplant at the NIH Clinical Center

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this

study:

• Pregnancy or lactation

• Unable to comply with study procedures

• Inability to provide written informed consent

Related Conditions & MeSH terms

• Hematopoietic Stem Cell Transplant
• Liver Diseases

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Death or total bilirubin >=4 at 91 days after the transplant	To determine whether, at 91 days after transplant, patients with liver disease at transplant are more likely to have died or have a total bilirubin >=4 than those without liver disease at transplant.	91 days after transplant
Primary	Mortality rate	To determine whether, at 91 days after transplant, patients with liver disease at transplant are more likely to have died or have a total bilirubin >=4 than those without liver disease at transplant.	91 days after transplant
Secondary	Rate of infection (type: bacterial, viral, fungal; location: central line, organ infection, sepsis, etc.)		91 days after transplant
Secondary	Development of portal hypertension and sequelae (i.e., ascites, variceal bleed, thrombocytopenia, elevated portal pressure)		91 days after transplant
Secondary	Morbitity/cause of death		91 days after transplant
Secondary	Development of liver failure	i.e., coagulopathy with an International Normalized Ratio (INR) 1.5, and any degree of mental alteration (encephalopathy) in a subject without preexisting cirrhosis and with an illness of <26 weeks duration, including patients with Wilson s disease, vertically acquired HBV, or autoimmune hepatitis per AASLD guidelines 2011.	91 days after transplant

External Links

•   NIH Clinical Center Detailed Web Page