4-PBA: Will it Increase the Level of Alpha 1-Antitrypsin(AAT) in Persons With AAT Deficiency? - Full Text View

Sponsor:	University of Florida
Collaborators:	Alpha-1 Foundation Brantly, Mark L., M.D.
Information provided by:	University of Florida
ClinicalTrials.gov Identifier:	NCT00067756

Purpose

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.

Condition	Intervention	Phase
Alpha 1-Antitrypsin Deficiency	Drug: 4 Phenyl Butyrate (4PBA)	Phase II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Safety/Efficacy Study
Official Title:	"4 Phenyl Butyrate Mediated Secretion Rescue in Alpha 1-Antitrypsin Deficient Individuals"

Resource links provided by NLM:

Genetics Home Reference related topics: alpha-1 antitrypsin deficiency

MedlinePlus related topics: Alpha-1 Antitrypsin Deficiency Liver Diseases

U.S. FDA Resources

Further study details as provided by University of Florida:

Primary Outcome Measures:

To determine if 4-PBA significantly increases secretion of AAT in AAT-deficient individuals with and without liver disease. [ Time Frame: 10 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To determine the pharmacokinetics of 4-PBA [ Time Frame: 10 days ] [ Designated as safety issue: Yes ]

Enrollment:	12
Study Start Date:	November 2001
Study Completion Date:	October 2003
Primary Completion Date:	October 2003 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
4-PBA: Experimental The study will involve a dose escalation and pharmacokinetics component The study group will be comprised of a total of 10 patients equally divided into PiZZ* AAT-deficient individuals with (n=5) and without (n=5) clinical evidence of mild to moderate hepatocellular injury.	Drug: 4 Phenyl Butyrate (4PBA) 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

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.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00067756

Locations

United States, Florida
University of Florida
Gainesville, Florida, United States, 32610

Sponsors and Collaborators

University of Florida

Alpha-1 Foundation

Brantly, Mark L., M.D.

Investigators

Principal Investigator:

Mark L Brantly, MD

University of Florida

More Information

Additional Information:

Alpha-1 Foundation Alpha-1 Research Program This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	University of Florida ( Mark L. Brantly, MD )
Study ID Numbers:	87-2001
Study First Received:	August 26, 2003
Last Updated:	February 17, 2009
ClinicalTrials.gov Identifier:	NCT00067756 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Florida:

Pulmonary Disease
Liver Disease

Additional relevant MeSH terms:

Serine Proteinase Inhibitors
Alpha 1-Antitrypsin
Molecular Mechanisms of Pharmacological Action
Alpha 1-Antitrypsin Deficiency
Trypsin Inhibitors

Connective Tissue Diseases
Enzyme Inhibitors
Pharmacologic Actions
Protease Inhibitors

ClinicalTrials.gov processed this record on November 25, 2009