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

NCT ID: NCT00067756

Last Updated: 2014-01-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-11-30
• Study Completion Date: 2003-10-31

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.

Conditions

Alpha 1-Antitrypsin Deficiency

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

4-PBA

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Other Intervention Names

4-phenyl butyric acid

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Alpha-1 Foundation

OTHER

Sponsor Role: collaborator

Brantly, Mark L., M.D.

INDIV

Sponsor Role: collaborator

University of Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark L Brantly, MD

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Locations

University of Florida

Gainesville, Florida, United States

Countries

United States

References

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

Reference Type: RESULT

Related Links

http://www.alphaone.ufl.edu

Alpha-1 Foundation Alpha-1 Research Program

Other Identifiers

87-2001

Identifier Type: -

Identifier Source: org_study_id