Liver Fibrosis in Alpha-1 Antitrypsin Deficiency (AATD)
Overview[ - collapse ][ - ]
Purpose | 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. |
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Condition | Liver Fibrosis Alpha-1 Antitrypsin Deficiency AAT Deficiency AATD |
Intervention | Device: Abdominal ultrasound Procedure: History and physical Procedure: Intravenous catheter Procedure: Blood draw Other: Liver questionnaire Procedure: Liver Biopsy Drug: Midazolam Drug: Fentanyl Drug: Lidocaine Drug: Acetaminophen Drug: Lorazepam Drug: Oxycodone/Acetaminophen Drug: Ondansetron |
Phase | Phase 1 |
Sponsor | University of Florida |
Responsible Party | University of Florida |
ClinicalTrials.gov Identifier | NCT01810458 |
First Received | March 6, 2013 |
Last Updated | October 28, 2013 |
Last verified | October 2013 |
Tracking Information[ + expand ][ + ]
First Received Date | March 6, 2013 |
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Last Updated Date | October 28, 2013 |
Start Date | October 2013 |
Estimated Primary Completion Date | April 2017 |
Current Primary Outcome Measures | To estimate the prevalence and histologic spectrum of liver injury in an adult with Alpha-1 Antitrypsin deficiency and a genotype of ZZ. [Time Frame: up to 30 days] [Designated as safety issue: No]An abdominal ultrasound will be done at the screening visit. A liver biopsy will be done on subjects who pass the screening process. The biopsy will be done within 30 days of the screening visit. |
Current Secondary Outcome Measures |
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Descriptive Information[ + expand ][ + ]
Brief Title | Liver Fibrosis in Alpha-1 Antitrypsin Deficiency (AATD) |
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Official Title | Clinical Predictors and Epigenetic Markers for Liver Fibrosis in Alpha-1 Antitrypsin Deficiency |
Brief Summary | 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. |
Detailed Description | Our overarching hypothesis is that liver disease in adults with AAT deficiency is the result of the accumulation of the abnormally folded protein within the endoplasmic reticulum of the hepatocyte. In some individuals, the intrinsic cellular mechanisms of the hepatocyte are sufficient to clear adequate amounts of the abnormally folded protein such that liver disease does not occur. In AAT deficient individuals who develop liver disease, environmental and other genetic factors stress the hepatocyte, and the normal cellular mechanisms that maintain homeostasis are disrupted, leading to liver disease. For this proposal, our hypothesis is that the prevalence of liver disease in adults with AAT is higher than previously reported because liver injury and fibrosis is not accurately detected by available routine liver testing. Testing this hypothesis will require an initial evaluation for liver disease with liver function testing and imaging, and then histologic confirmation by liver biopsy. |
Study Type | Interventional |
Study Phase | Phase 1 |
Study Design | Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Screening |
Condition |
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Intervention | Device: Abdominal ultrasound Abdominal ultrasound will be done at the screening visit and year 3 visit. The purpose of the ultrasound is to evaluate for the presence of liver fibrosis. Other Names: SonoSite Edge Ultrasound SystemProcedure: History and physical Every 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. Other Names:
Every 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. Other Names: IVProcedure: Blood draw At 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 Names: PhlebotomyOther: Liver questionnaire At the screening and year 3 visits, every subject will complete a questionnaire which involves questions regarding liver health. Other Names: QuestionnaireProcedure: Liver Biopsy Every 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. Other Names: BiopsyDrug: Midazolam Every 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). Other Names: VersedDrug: Fentanyl Every 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). Other Names:
Every 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). Other Names: XylocaineDrug: Acetaminophen Every 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). Other Names: TylenolDrug: Lorazepam Every 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). Other Names: AtivanDrug: Oxycodone/Acetaminophen Every 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). Other Names:
Every 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). Other Names: Zofran |
Study Arm (s) | Experimental: AATD ZZ Group Participants will get a history and physical (H&P) and have an intravenous catheter (IV) placed, for blood draws, at the screening and years 1-3 visits. An IV will also be placed at the liver biopsy visit(s) for the administration of medication. An abdominal ultrasound will be done at the screening and year 3 visits along with the completion of a liver questionnaire. Finally, participants will have a liver biopsy done, with the use of lidocaine, lorazepam, or midazolam and fentanyl, after the screening visit and potentially at the year 3 study visit, depending on the results of the first liver biopsy. Participants who experience pain after the liver biopsy may receive acetaminophen or oxycodone/acetaminophen. Any subject experiencing nausea may receive ondansetron. |
Recruitment Information[ + expand ][ + ]
Recruitment Status | Recruiting |
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Estimated Enrollment | 100 |
Estimated Completion Date | April 2017 |
Estimated Primary Completion Date | April 2016 |
Eligibility Criteria | Inclusion Criteria: - Alpha-1 Antitrypsin deficiency confirmed to be PI*ZZ by both genotype and phenotype who have serum AAT levels less than or equal to 11 µM; - Age range from 21-70; - Willingness to consent to liver biopsy; - Ability to travel to UF as necessary by protocol; and - Platelet count greater than or equal to 75,000/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. |
Gender | Both |
Ages | 21 Years |
Accepts Healthy Volunteers | No |
Contacts | Contact: Tracie L Kurtz, RN 866-229-6313 tlkurtz@ufl.edu |
Location Countries | United States |
Administrative Information[ + expand ][ + ]
NCT Number | NCT01810458 |
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Other Study ID Numbers | 63-2013 |
Has Data Monitoring Committee | No |
Information Provided By | University of Florida |
Study Sponsor | University of Florida |
Collaborators | Not Provided |
Investigators | Principal Investigator: Mark Brantly, MD University of Florida |
Verification Date | October 2013 |
Locations[ + expand ][ + ]
Shands at the University of Florida | Gainesville, Florida, United States, 32610 Contact: Tracie L Kurtz, RN | 866-229-6313 | tlkurtz@ufl.eduPrincipal Investigator: Mark Brantly, MD Recruiting |
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