Liver FibrosisNCT01810458
Liver Fibrosis in Alpha-1 Antitrypsin Deficiency (Liver AATD)
An observational study of Liver Fibrosis and Alpha-1 Antitrypsin Deficiency, run by University of Florida at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Liver Fibrosis, Alpha-1 Antitrypsin Deficiency, AAT Deficiency
- What is being tested?
- Abdominal ultrasound, History and physical and Intravenous catheter
- Type of treatment
- Injection or infusion, Medical device, Surgery or procedure
- How many people
- 109 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2013to Sep 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Pulmonary clinic, hepatology clinic, and the Alpha-1 Antitrypsin Tissue and Data Bank.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Shands at the University of Florida
Gainesville, Florida, 32610
About this study
Official title: Clinical Predictors and Epigenetic Markers for Liver Fibrosis in Alpha-1 Antitrypsin Deficiency
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.
Read the 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.
- Conditions
- Liver Fibrosis, Alpha-1 Antitrypsin Deficiency, AAT Deficiency, AATD
- Being tested
- Abdominal ultrasound, History and physical, Intravenous catheter, Blood draw, Liver questionnaire
- Keywords
- Liver, Fibrosis, Alpha-1, AAT, AATD
- Medical subject headings
- Liver Cirrhosis, alpha 1-Antitrypsin Deficiency, Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Abdominal ultrasoundDevice
Also called SonoSite Edge Ultrasound System
Abdominal 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.
History and physicalProcedure or surgery
Also called H&P, exam, medical history
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.
Intravenous catheterProcedure or surgery
Also called IV
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.
Blood drawProcedure or surgery
Also called Phlebotomy
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.
Liver questionnaireOther
Also called Questionnaire
At the screening and year 3 visits, every subject will complete a questionnaire which involves questions regarding liver health.
Liver BiopsyProcedure or surgery
Also called 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.
MidazolamDrug
Also called Versed
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).
FentanylDrug
Also called Fentora, Onsolis
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).
LidocaineDrug
Also called Xylocaine
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).
AcetaminophenDrug
Also called Tylenol
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).
LorazepamDrug
Also called Ativan
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).
Oxycodone/AcetaminophenDrug
Also called Percocet, Tylox
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).
OndansetronDrug
Also called Zofran
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).
| Study group | Role | What they receive |
|---|---|---|
| AATD ZZ and Rare Alleles 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. Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
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.
Measured: up to 30 days
Secondary outcomes (4)
To identify environmental and host risk factors for clinically significant liver fibrosis.
A liver disease questionnaire will be done at the time of the first liver biopsy and at the year 3 study visit. A history and physical will also be completed at the screening visit, year 1 visit, year 2 visit, and year 3 visit.
Measured: At each study visit including screening, first liver biopsy, year 1, year 2, and year 3 visits.
To define the diagnostic accuracy of non-invasive markers of fibrosis in AAT liver disease.
An abdominal ultrasound will be completed at the screening visit and the year 3 visit.
Measured: At the screening and year 3 visits.
To explore epigenetic markers for the development of liver fibrosis.
Liver tissue collected at the time of the first biopsy will be sent for testing which will evaluate for epigenetic markers of liver fibrosis. For subjects whose initial liver biopsy reveals liver fibrosis between stages 2 - 4, additional liver tissue will be collected at the time of the repeat biopsy done at the year 3 study visit.
Measured: Starting with the first liver biopsy and ending with the second liver biopsy done at year 3.
To quantify liver fibrosis progression.
The presence and progression of liver fibrosis will be evaluated by an abdominal ultrasound done at the screening visit, year 1 visit, year 2 visit, and year 3 visit. A liver biopsy will be done if a subject passes the screening visit and will be repeated at the year 3 study visit if the initial liver biopsy reveals liver fibrosis between stages 2 - 4.
Measured: At each study visit including screening, first liver biopsy, year 1, year 2, and year 3 visits.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2013 (estimated)
- Study startOct 2013
- Primary completionSep 2019
- Study completionSep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Liver FibrosisStudies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 109 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mark Brantly, MD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01810458
- Sponsor's protocol ID
- IRB201601019
- Other IDs
- 910, IRB201601019/ 63-2013
- Status last verified
- Aug 2023
- First submitted
- 6 Mar 2013
- Last updated
- 21 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Enrolled subjects will receive copies of all their clinical testing done while enrolled in the study. Otherwise, all data for publication purposes will be de-identified.
Publications
Clark VC, Marek G, Liu C, Collinsworth A, Shuster J, Kurtz T, Nolte J, Brantly M. Clinical and histologic features of adults with alpha-1 antitrypsin deficiency in a non-cirrhotic cohort. J Hepatol. 2018 Dec;69(6):1357-1364. doi: 10.1016/j.jhep.2018.08.005. Epub 2018 Aug 21.
PubMed 30138687
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Predictors and Epigenetic Markers for Liver Fibrosis in Alpha-1 Antitrypsin Deficiency
- ClinicalTrials.gov ID
- NCT01810458
- Acronym / sponsor ID
- IRB201601019
- Conditions
- Liver Fibrosis, Alpha-1 Antitrypsin Deficiency, AAT Deficiency, AATD
- Keywords
- Liver, Fibrosis, Alpha-1, AAT, AATD
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 109 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Study start
- Oct 2013 (actual)
- Primary completion
- Sep 2019 (actual)
- Study completion
- Sep 2019 (actual)
- First posted
- 13 Mar 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AATD ZZ and Rare Alleles Group | – | 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: OndansetronParticipants 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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Pulmonary clinic, hepatology clinic, and the Alpha-1 Antitrypsin Tissue and Data Bank.
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Abdominal ultrasoundAlso: SonoSite Edge Ultrasound SystemAbdominal 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. | Device | AATD ZZ and Rare Alleles Group |
| History and physicalAlso: H&P, exam, medical historyEvery 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 or surgery | AATD ZZ and Rare Alleles Group |
| Intravenous catheterAlso: IVEvery 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 or surgery | AATD ZZ and Rare Alleles Group |
| Blood drawAlso: PhlebotomyAt 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. | Procedure or surgery | AATD ZZ and Rare Alleles Group |
| Liver questionnaireAlso: QuestionnaireAt the screening and year 3 visits, every subject will complete a questionnaire which involves questions regarding liver health. | Other | AATD ZZ and Rare Alleles Group |
| Liver BiopsyAlso: 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. | Procedure or surgery | AATD ZZ and Rare Alleles Group |
| MidazolamAlso: VersedEvery 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 | AATD ZZ and Rare Alleles Group |
| FentanylAlso: Fentora, OnsolisEvery 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 | AATD ZZ and Rare Alleles Group |
| LidocaineAlso: XylocaineEvery 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 | AATD ZZ and Rare Alleles Group |
| AcetaminophenAlso: TylenolEvery 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 | AATD ZZ and Rare Alleles Group |
| LorazepamAlso: AtivanEvery 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 | AATD ZZ and Rare Alleles Group |
| Oxycodone/AcetaminophenAlso: Percocet, TyloxEvery 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 | AATD ZZ and Rare Alleles Group |
| OndansetronAlso: ZofranEvery 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 | AATD ZZ and Rare Alleles Group |
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.
Time frame: up to 30 days
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.
4 secondary outcomes
To identify environmental and host risk factors for clinically significant liver fibrosis.
Time frame: At each study visit including screening, first liver biopsy, year 1, year 2, and year 3 visits.
To define the diagnostic accuracy of non-invasive markers of fibrosis in AAT liver disease.
Time frame: At the screening and year 3 visits.
To explore epigenetic markers for the development of liver fibrosis.
Time frame: Starting with the first liver biopsy and ending with the second liver biopsy done at year 3.
To quantify liver fibrosis progression.
Time frame: At each study visit including screening, first liver biopsy, year 1, year 2, and year 3 visits.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2023.
- Derived from this study: PubMed 30138687Clark VC, Marek G, Liu C, Collinsworth A, Shuster J, Kurtz T, Nolte J, Brantly M. Clinical and histologic features of adults with alpha-1 antitrypsin deficiency in a non-cirrhotic cohort. J Hepatol. 2018 Dec;69(6):1357-1364. doi: 10.1016/j.jhep.2018.08.005. Epub 2018 Aug 21.
- Individual participant dataSharing planned: Yes. Enrolled subjects will receive copies of all their clinical testing done while enrolled in the study. Otherwise, all data for publication purposes will be de-identified.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark Brantly, MD principal investigator
University of Florida
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Liver Fibrosis and Alpha-1 Antitrypsin Deficiency, run by University of Florida 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 6 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 21 Aug 2023. 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?
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. (time frame: up to 30 days). 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 NCT01810458, which also lists 1 linked publication.
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 21 Aug 2023.