Clinical Trial: Epigenetic Regulation of Immunity in Alpha-1 Anti-trypsin Deficiency
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational
Official Title: Defining Epigenetic Regulation of Immunity in Alpha-1 Anti-trypsin Deficiency
Brief Summary: The investigators hypothesize that environmentally influenced histone modifications regulate AM mediated inflammation, contributing to a variable clinical course of AATD, and may also influence or be influenced by the activity of AAT augmentation therapy.
Detailed Summary:
The variable natural clinical course of alpha-1 anti-trypsin deficiency (AATD) disease and strong influence of environmental exposures such as smoking, implicate a major role for epigenetic mechanisms in modifying AATD disease penetrance. The goal of this study proposal is to investigate epigenetic regulation of alveolar macrophage (AM) inflammation and function in AATD PiZZ patients. The investigators proposal focuses on epigenetic histone modifications and gene expression specifically in AM.
AAT augmentation therapy, which alters disease symptoms, may also modulate AM epigenetics. To identify epigenetic regulation of AM inflammation in AATD in the context of AAT therapy, the investigators will perform and computationally integrate ChIP-seq and RNA-seq data. This will help elucidate the immunomodulatory mechanisms regulating AATD and provide an epigenetic map for diagnosis and targeted treatment. The investigators will test the efficacy of FDA-approved histone modifying drugs, such as SAHA and more specific next-generation histone modifiers, such as GSK-J4, to modulate AM AATD-associated activity ex vivo.
The goal of this study is to enroll up to a total of 13 AATD cases and 6 healthy controls. All AATD patients will be asked to give a blood sample and undergo a bronchoscopy. AATD patients will also be asked to undergo a follow up bronchoscopy and blood draw after 6 months of treatment with alpha-1 antitrypsin augmentation therapy to study the changes in these markers after augmentation therapy.
Sponsor: National Jewish Health
Current Primary Outcome: Epigenetic signature of specific inflammation-associated histone modifications from CD14+ macrophages [ Time Frame: Change from Baseline histones at 6 months ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
- Epigenetically regulated genomic profile of AATD in AM [ Time Frame: Change from Baseline polyA RNA at 6 months ]
- Epigenetic mechanisms to regulate gene expression and cell function [ Time Frame: Change from Baseline epigenetic modified cells at 6 months ]
Original Secondary Outcome: Same as current
Information By: National Jewish Health
Dates:
Date Received: February 12, 2016
Date Started: December 2015
Date Completion: November 2020
Last Updated: September 20, 2016
Last Verified: September 2016
