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

This study has been completed.
Alpha-1 Foundation
Brantly, Mark L., M.D.
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
First received: August 26, 2003
Last updated: January 2, 2014
Last verified: April 2013

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-PBA
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: "4 Phenyl Butyrate Mediated Secretion Rescue in Alpha 1-Antitrypsin Deficient Individuals"

Resource links provided by NLM:

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
Experimental: 4-PBA
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.
Drug: 4-PBA
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
Other Name: 4-phenyl butyric acid

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.


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

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

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.
Principal Investigator: Mark L Brantly, MD University of Florida
  More Information

Additional Information:
No publications provided

Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT00067756     History of Changes
Other Study ID Numbers: 87-2001
Study First Received: August 26, 2003
Last Updated: January 2, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Florida:
Pulmonary Disease
Liver Disease

Additional relevant MeSH terms:
Alpha 1-Antitrypsin Deficiency
Digestive System Diseases
Genetic Diseases, Inborn
Liver Diseases
Lung Diseases
Pathologic Processes
Respiratory Tract Diseases
Subcutaneous Emphysema
Alpha 1-Antitrypsin
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protease Inhibitors
Serine Proteinase Inhibitors
Trypsin Inhibitors

ClinicalTrials.gov processed this record on May 21, 2015