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

This study has been completed.
Sponsor:
Collaborators:
Alpha-1 Foundation
Brantly, Mark L., M.D.
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
NCT00067756
First received: August 26, 2003
Last updated: January 2, 2014
Last verified: April 2013
  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-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.

  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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:
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
Liver Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Subcutaneous Emphysema
Emphysema
Pathologic Processes
Alpha 1-Antitrypsin
Butyric Acid
Trypsin Inhibitors
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Histamine Antagonists
Histamine Agents
Neurotransmitter Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 26, 2014