Back to results4-PBA: Will it Increase the Level of Alpha 1-Antitrypsin(AAT) in Persons With AAT Deficiency?
Primary Purpose
Alpha 1-Antitrypsin Deficiency
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
4-PBA
Sponsored by
About this trial
This is an interventional treatment trial for Alpha 1-Antitrypsin Deficiency focused on measuring Pulmonary Disease, Liver Disease
Eligibility Criteria
Inclusion Criteria: Age 18-65 Serum A1-PI levels <11uM an appropriate genetic phenotype/genotype 5 of 10 subjects must have documented laboratory evidence of liver disease Willingness to withhold Prolastin therapy for 6 weeks prior to screening and throughout the 4-PBA dosing period (up to 3 months) Exclusion Criteria: Any cause of liver disease other than Alpha-1 Antitrypsin deficiency Evidence of advanced liver disease HIV positive Use of systemic steroids, ursodeoxycholic acid (Actigall, Urso), or herbs in the prior 6 months
Sites / Locations
- University of Florida
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
4-PBA
Arm Description
The study will involve a 4-PBA dose escalation and pharmacokinetics component The study group will be comprised of a total of at least 10 AAT-deficient,(phenotype ZZ referred to as PiZZ) patients. These patients will be divided into two groups: with and without clinical evidence of mild to moderate hepatocellular injury.
Outcomes
Primary Outcome Measures
To determine if 4-PBA significantly increases secretion of AAT in AAT-deficient individuals with and without liver disease.
Secondary Outcome Measures
To determine the pharmacokinetics of 4-PBA
Full Information
NCT ID
NCT00067756
First Posted
August 26, 2003
Last Updated
January 2, 2014
Sponsor
University of Florida
Collaborators
Alpha-1 Foundation, Brantly, Mark L., M.D.
1. Study Identification
Unique Protocol Identification Number
NCT00067756
Brief Title
4-PBA: Will it Increase the Level of Alpha 1-Antitrypsin(AAT) in Persons With AAT Deficiency?
Official Title
"4 Phenyl Butyrate Mediated Secretion Rescue in Alpha 1-Antitrypsin Deficient Individuals"
Study Type
Interventional
2. Study Status
Record Verification Date
April 2013
Overall Recruitment Status
Completed
Study Start Date
November 2001 (undefined)
Primary Completion Date
October 2003 (Actual)
Study Completion Date
October 2003 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Florida
Collaborators
Alpha-1 Foundation, Brantly, Mark L., M.D.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to find out whether 4-PBA will increase the level of AAT in persons with AAT deficiency whether or not they have liver disease.
Detailed Description
The purpose of this study is to determine whether 4-PBA will significantly increase serum Z AAT levels in AAT-deficient individuals with and without evidence of hepatocellular injury and to assess its effects on liver injury.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alpha 1-Antitrypsin Deficiency
Keywords
Pulmonary Disease, Liver Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
4-PBA
Arm Type
Experimental
Arm Description
The study will involve a 4-PBA dose escalation and pharmacokinetics component The study group will be comprised of a total of at least 10 AAT-deficient,(phenotype ZZ referred to as PiZZ) patients. These patients will be divided into two groups: with and without clinical evidence of mild to moderate hepatocellular injury.
Intervention Type
Drug
Intervention Name(s)
4-PBA
Other Intervention Name(s)
4-phenyl butyric acid
Intervention Description
During the first 3 days of this phase baseline serum AAT levels will be determined. The participants will be then given increased amounts of 4-PBA orally in 6 divided doses (day 4-6, 30 g/day and day 7-9, 40/day
Primary Outcome Measure Information:
Title
To determine if 4-PBA significantly increases secretion of AAT in AAT-deficient individuals with and without liver disease.
Time Frame
10 days
Secondary Outcome Measure Information:
Title
To determine the pharmacokinetics of 4-PBA
Time Frame
10 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age 18-65
Serum A1-PI levels <11uM an appropriate genetic phenotype/genotype
5 of 10 subjects must have documented laboratory evidence of liver disease
Willingness to withhold Prolastin therapy for 6 weeks prior to screening and throughout the 4-PBA dosing period (up to 3 months)
Exclusion Criteria:
Any cause of liver disease other than Alpha-1 Antitrypsin deficiency
Evidence of advanced liver disease
HIV positive
Use of systemic steroids, ursodeoxycholic acid (Actigall, Urso), or herbs in the prior 6 months
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark L Brantly, MD
Organizational Affiliation
University of Florida
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
12. IPD Sharing Statement
Citations:
Citation
Gonzalez-Peralta RP, Leonard S, Harvey R, Schreck P, Vironosvkaya N, Brantly ML. 4-PHENYL BUTYRATE MEDIATED SECRETION RESCUE IN PATIENTS WITH ALPHA 1-ANTITRYPSIN (AAT) DEFICIENCY: A PILOT STUDY HEPATOLOGY, Vol. 44, No. 4, Suppl. 1, 2006 AASLD ABSTRACTS, p. 211A, 61
Results Reference
result
Links:
URL
http://www.alphaone.ufl.edu
Description
Alpha-1 Foundation Alpha-1 Research Program
Learn more about this trial
4-PBA: Will it Increase the Level of Alpha 1-Antitrypsin(AAT) in Persons With AAT Deficiency?
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