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Liver Fibrosis | Liver Fibrosis in Alpha-1 Antitrypsin Deficiency (AATD)

Liver Fibrosis research study

What is the primary objective of this study?

We hypothesize that individuals with Alpha-1 Antitrypsin (AAT) deficiency have ongoing liver injury which is not detected by the usual blood tests used to look at liver function. This ongoing liver injury leads to cirrhosis in a significant number of adults with AAT deficiency.

Who is eligible to participate?

Inclusion Criteria: - Alpha-1 Antitrypsin deficiency confirmed to be PI*ZZ by both genotype or another identified rare allele; - Age range from 18-70; - Willingness to consent to liver biopsy; - Ability to travel to UF as necessary by protocol; and - Platelet count greater than or equal to 50,000/mm3 and an INR less than or equal to 1.5. Exclusion Criteria: - Hemophilia, anticoagulant therapy that cannot be interrupted briefly, malignancy, or any other condition that would compromise the safety of a liver biopsy; - Any known pre-existing medical condition that might interfere with the patient's participation in and completion of the study or any condition, which in the opinion of the investigator would make the patient unsuitable for enrollment; - Active substance abuse including, but not limited to, alcohol, intravenous or, inhaled drugs; - History of adverse reactions or allergy to the local anesthetic, sedative, or pre-medication used for the percutaneous liver biopsy; - Poor venous access making the subject unable to complete the required laboratory testing schedule; and - Females who are pregnant or lactating at time of enrollment. Should a female subject become pregnant during the follow up period after the initial liver biopsy, continued participation would be allowed if the following conditions are met: the subject desires to continue; a discussion of risk and benefits of participation between the principal investigator and the subject has occurred; and no liver biopsy would be performed in the follow up period.

Which medical condition, disease, disorder, syndrome, illness, or injury is researched?

Liver Fibrosis

Alpha-1 Antitrypsin Deficiency

AAT Deficiency

AATD

Study Interventions

Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.

Device:Abdominal ultrasoundAbdominal ultrasound will be done at the liver biopsy visits. The purpose of the ultrasound is to evaluate for the presence of liver fibrosis and identify the biopsy site.

Procedure:History and physicalEvery study participant will be asked about their medical history and will have a physical exam done at the screening, year 1, year 2, and year 3 visits.

Procedure:Intravenous catheterEvery study participant will have and intravenous catheter (IV) placed at every study visit. The IV will be used for the collection of blood at the screening, year 2, year 2, and year 3 visits. It will also be used for the administration of medication at the first liver biopsy, as well as the year 3 visit if the biopsy is repeated.

Procedure:Blood drawAt the screening, year 1, year 2, and year 3 visits, every participant will have blood collected from the IV that is placed in one of their veins.

Other:Liver questionnaireAt the screening and year 3 visits, every subject will complete a questionnaire which involves questions regarding liver health.

Procedure:Liver BiopsyEvery participating subject who passes the screening visit, will have a liver biopsy done with the use of lidocaine (a numbing medicine) injected into skin where the biopsy will be collected. At the time of the biopsy, either lorazepam (a medicine used to treat anxiety and cause relaxation) or midazolam (a medicine used to cause sleepiness and amnesia) and fentanyl (a medicine used to relieve pain) will be used. Once the relaxation medication and numbing medicine have been given, a sample of liver tissue will be collected using a needle biopsy device.

Drug:MidazolamEvery participating subject who passes the screening visit, will have a liver biopsy done with the use of lidocaine injected into skin where the biopsy will be collected. At the time of the biopsy, either lorazepam (a medicine used to treat anxiety and cause relaxation) or midazolam (a medicine used to cause sleepiness and amnesia) and fentanyl (a medicine used to relieve pain) will be used. After the biopsy is done, participants who continue to have pain may receive either oxycodone/acetaminophen or acetaminophen (medicines used to relieve pain). Any participant who experiences nausea may receive ondansetron (a medicine used to relieve nausea).

Drug:FentanylEvery participating subject who passes the screening visit, will have a liver biopsy done with the use of lidocaine injected into skin where the biopsy will be collected. At the time of the biopsy, either lorazepam (a medicine used to treat anxiety and cause relaxation) or midazolam (a medicine used to cause sleepiness and amnesia) and fentanyl (a medicine used to relieve pain) will be used. After the biopsy is done, participants who continue to have pain may receive either oxycodone/acetaminophen or acetaminophen (medicines used to relieve pain). Any participant who experiences nausea may receive ondansetron (a medicine used to relieve nausea).

Drug:LidocaineEvery participating subject who passes the screening visit, will have a liver biopsy done with the use of lidocaine injected into skin where the biopsy will be collected. At the time of the biopsy, either lorazepam (a medicine used to treat anxiety and cause relaxation) or midazolam (a medicine used to cause sleepiness and amnesia) and fentanyl (a medicine used to relieve pain) will be used. After the biopsy is done, participants who continue to have pain may receive either oxycodone/acetaminophen or acetaminophen (medicines used to relieve pain). Any participant who experiences nausea may receive ondansetron (a medicine used to relieve nausea).

Drug:AcetaminophenEvery participating subject who passes the screening visit, will have a liver biopsy done with the use of lidocaine injected into skin where the biopsy will be collected. At the time of the biopsy, either lorazepam (a medicine used to treat anxiety and cause relaxation) or midazolam (a medicine used to cause sleepiness and amnesia) and fentanyl (a medicine used to relieve pain) will be used. After the biopsy is done, participants who continue to have pain may receive either oxycodone/acetaminophen or acetaminophen (medicines used to relieve pain). Any participant who experiences nausea may receive ondansetron (a medicine used to relieve nausea).

Drug:LorazepamEvery participating subject who passes the screening visit, will have a liver biopsy done with the use of lidocaine injected into skin where the biopsy will be collected. At the time of the biopsy, either lorazepam (a medicine used to treat anxiety and cause relaxation) or midazolam (a medicine used to cause sleepiness and amnesia) and fentanyl (a medicine used to relieve pain) will be used. After the biopsy is done, participants who continue to have pain may receive either oxycodone/acetaminophen or acetaminophen (medicines used to relieve pain). Any participant who experiences nausea may receive ondansetron (a medicine used to relieve nausea).

Drug:Oxycodone/AcetaminophenEvery participating subject who passes the screening visit, will have a liver biopsy done with the use of lidocaine injected into skin where the biopsy will be collected. At the time of the biopsy, either lorazepam (a medicine used to treat anxiety and cause relaxation) or midazolam (a medicine used to cause sleepiness and amnesia) and fentanyl (a medicine used to relieve pain) will be used. After the biopsy is done, participants who continue to have pain may receive either oxycodone/acetaminophen or acetaminophen (medicines used to relieve pain). Any participant who experiences nausea may receive ondansetron (a medicine used to relieve nausea).

Drug:OndansetronEvery participating subject who passes the screening visit, will have a liver biopsy done with the use of lidocaine injected into skin where the biopsy will be collected. At the time of the biopsy, either lorazepam (a medicine used to treat anxiety and cause relaxation) or midazolam (a medicine used to cause sleepiness and amnesia) and fentanyl (a medicine used to relieve pain) will be used. After the biopsy is done, participants who continue to have pain may receive either oxycodone/acetaminophen or acetaminophen (medicines used to relieve pain). Any participant who experiences nausea may receive ondansetron (a medicine used to relieve nausea).

Study Arms

Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.

AATD ZZ and Rare Alleles Group

Study Status

Active, not recruiting

Start Date: October 2013

Completed Date: October 2020

Phase: N/A

Type: Observational

Design:

Primary Outcome: To estimate the prevalence and histologic spectrum of liver injury in an adult with Alpha-1 Antitrypsin deficiency having a ZZ genotype or other rare allele.

Secondary Outcome: To identify environmental and host risk factors for clinically significant liver fibrosis.

Study sponsors, principal investigator, and references

Principal Investigator: Mark Brantly, MD

Lead Sponsor: University of Florida

Collaborator:

More information:https://clinicaltrials.gov/show/NCT01810458

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