Epigenetic Regulation of Immunity in Alpha-1 Anti-trypsin Deficiency

NCT02691611 | Completed DMC

• 1 other identifier: HS-2939
• Study Type: observational
• Target: 39
• Locations: 1 country
• Sites: 1

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.

Conditions

Alpha 1-Antitrypsin Deficiency

Outcome Measures

Primary Outcomes (1)

• Epigenetic signature of specific inflammation-associated histone modifications from CD14+ macrophages

  Change from Baseline histones at 6 months

Secondary Outcomes (2)

• Epigenetically regulated genomic profile of AATD in AM

  Change from Baseline polyA RNA at 6 months

• Epigenetic mechanisms to regulate gene expression and cell function

  Change from Baseline epigenetic modified cells at 6 months

Study Arms (2)

Alpha-1 Antitrypsin

All AATD patients who will start treatment with alpha-1 antitrypsin augmentation therapy

Healthy Control

Healthy controls with no lung diseases

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

* AATD from clinic * Healthy controls from community

You may qualify if:

• AATD
• Age between the ages of 18 and 85
• Have a diagnosis of AATD PiZZ or PiMZ established by AAT blood levels and Pi genotyping
• Are not and have not been on AAT augmentation therapy for the past 6 months
• Able to tolerate and willing to undergo study procedures
• Provide signed informed consent.

You may not qualify if:

• AATD
• History of comorbid condition severe enough to significantly increase risks based on investigator discretion
• Diagnosis of unstable cardiovascular disease including myocardial infarction in the past 6 weeks, uncontrolled congestive heart failure, or uncontrolled arrhythmia
• Partial Pressure of Oxygen (PaO2) on room air at rest \<50 mmHg or Oxygen saturation (SaO2) on room air at rest \<85%
• Post bronchodilator Forced expiratory volume in one second (FEV1)\<30% predicted
• Use of anticoagulation (patients on warfarin or clopidogrel will be excluded; patients on aspirin alone can be studied even with concurrent use)
• Dementia or other cognitive dysfunction which in the opinion of the investigator would prevent the participant from consenting to the study or completing study procedures
• Active pulmonary infection with tuberculosis
• History of pulmonary embolism in the past 2 years
• Non-Chronic Obstructive Pulmonary Disease (COPD) obstructive disease (various bronchiolitides, sarcoid, lymphangioleiomyomatosis (LAM), histiocytosis X) or parenchymal lung disease, pulmonary vascular disease, pleural disease, severe kyphoscoliosis, neuromuscular weakness, or other cardiovascular and pulmonary disease, that, in the opinion of the investigator, limit the interpretability of the pulmonary function measures
• Prior significant difficulties with pulmonary function testing
• Hypersensitivity to or intolerance of albuterol sulfate or ipratropium bromide or propellants or excipients of the inhalers
• Hypersensitivity to or intolerance of all drugs required for sedation during conscious sedation bronchoscopy.
• History of Lung volume reduction surgery, lung resection or bronchoscopic lung volume reduction in any form
• History of lung or other organ transplant

Sponsors & Collaborators

• National Jewish Health: lead
• Medical University of South Carolina: collaborator

Study Sites (1)

National Jewish Health

Denver, Colorado, 80206, United States

Location

Related Publications (33)

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MeSH Terms

Conditions

alpha 1-Antitrypsin Deficiency

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Subcutaneous Emphysema; Emphysema; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2016
• First Posted: February 25, 2016
• Study Start: December 1, 2015
• Primary Completion: November 1, 2018
• Study Completion: July 1, 2020
• Last Updated: June 6, 2025

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)