Epigenetic Regulation of Immunity in Alpha-1 Anti-trypsin Deficiency (AATD_Epi)
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|ClinicalTrials.gov Identifier: NCT02691611|
Recruitment Status : Unknown
Verified March 2019 by National Jewish Health.
Recruitment status was: Active, not recruiting
First Posted : February 25, 2016
Last Update Posted : March 13, 2019
|Condition or disease|
|Alpha 1-Antitrypsin Deficiency|
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 (two Z genes) and PiMZ (one M and one Z gene) 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 Suberoylanilide Hydroxamic Acid (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/or undergo a bronchoscopy. AATD patients will also be asked to undergo a follow up bronchoscopy and/or blood draw after 6 months if treatment with alpha-1 antitrypsin augmentation therapy is initiated to study the changes in these markers after augmentation therapy.
|Study Type :||Observational|
|Actual Enrollment :||39 participants|
|Official Title:||Defining Epigenetic Regulation of Immunity in Alpha-1 Anti-trypsin Deficiency|
|Study Start Date :||December 2015|
|Actual Primary Completion Date :||November 2018|
|Estimated Study Completion Date :||November 2020|
All AATD patients who will start treatment with alpha-1 antitrypsin augmentation therapy
Healthy controls with no lung diseases
- Epigenetic signature of specific inflammation-associated histone modifications from CD14+ macrophages [ Time Frame: Change from Baseline histones at 6 months ]
- 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 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02691611
|United States, Colorado|
|National Jewish Health|
|Denver, Colorado, United States, 80206|
|Principal Investigator:||Brian P O'Connor, PhD||National Jewish Health|
|Principal Investigator:||Nabeel Y Hamzeh, MD||National Jewish Health|
|Principal Investigator:||Robert Sandhaus, MD, PhD||National Jewish Health|