Genomic Research in Sarcoidosis

NCT01831739 | Completed DMC

• 2 other identifiers: 13020130U01HL112707
• Study Type: observational
• Target: 368
• Locations: 1 country
• Sites: 9

Brief Summary

This project is designed to address the following hypothesis: Distinct patterns in lung microbiome are characteristic of sarcoidosis phenotypes and reflected in changes in systemic inflammatory responses as measured by peripheral changes in gene transcription. The Specific Aims are:

1. 1.To identify peripheral blood mononuclear cell (PBMC) gene expression patterns that characterize distinct sarcoidosis phenotypes.
2. 2.To determine whether patterns in the lung microbiome are associated with sarcoidosis severity and disease phenotypes
3. 3.To correlate mRNA and microRNA expression patterns in sarcoidosis affected organs with changes in microbiome, clinical parameters and PBMC gene expression patterns
4. 4.To integrate clinical, transcriptomic, and microbiome data to identify novel molecular phenotypes in sarcoidosis.

Conditions

Sarcoidosis

Keywords

Genomics; Microbiome; Microflora; Virome

Outcome Measures

Primary Outcomes (1)

• PBMC Gene Expression

  To identify peripheral blood mononuclear cell (PBMC) gene expression patterns that characterize distinct sarcoidosis phenotypes, samples will be run in batches in block designs (equal numbers of phenotypes) and batches will be analyzed independently to determine reproducibility - a subset of samples will be rerun to assure continuity and established normalization algorithms will be applied 1-3. Normalized human transcript (mRNA and microRNA) levels obtained from PBMC will be related to established phenotypes as well as cross phenotype characteristics using linear models, i.e., ANOVA or linear regression using the LIMMA package (http://bioinf.wehi.edu.au) or BRB ArrayTools (http://linus.nci.nih.gov/BRB-ArrayTools.html).

  Baseline, 6 months, 12 months

Study Arms (9)

Multi-organ

Non-acute presentation, any Scadding stage, evidence of 5 or more organ systems involved, chronic or uncertain clinical course.

Non-acute, Stage I, untreated

Non-acute presentation, Scadding stage I, no multi-organ involvement, chronic or uncertain clinical course, no cardiac manifestations, untreated for at least 3 months.

Stage II-III, treated

Non-acute presentation, Scadding stages II or III, no multi-organ involvement, chronic or uncertain clinical course, no cardiac manifestations, treated for at least 3 months.

Stage II-III, untreated

Non-acute presentation, Scadding stage II or III, no multi-organ involvement, chronic or uncertain clinical course, no cardiac manifestations, untreated for at least 3 months.

Stage IV treated

Non-acute presentation, Scadding stage IV, no multi-organ involvement, chronic or uncertain clinical course, no cardiac manifestations, treatment current and for at least 3 months.

Stage IV untreated

Non-acute presentation, Scadding stage IV, no multi-organ involvement, chronic or uncertain clinical course, no cardiac manifestations, untreated for at least 3 months.

Acute Sarcoidosis, untreated

Acute presentation, Scadding stages I, II, or III, chronic or uncertain clinical course, no cardiac manifestations, untreated for at least 3 months.

Remitting, untreated

Remitting clinical course, no treatment for at least 3 months.

Cardiac defining therapy

Chronic or uncertain clinical course, no multi-organ involvement, cardiac manifestations defining need for systemic corticosteroid and/or immunomodulatory therapy.

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Subjects will be prescreened for predefined clinical phenotypes of sarcoidosis. Those who meet initial criteria and ERS/ATS criteria for a sarcoidosis diagnosis will be recruited and phenotyped by questionnaire, physical exam, research chest CT exam, pulmonary function tests, and blood and urine tests with a total recruitment goal of 400. A subset of participants who have suspected pulmonary sarcoidosis, but who have not undergone a biopsy, will be recruited so that material may be obtained during their clinically indicated biopsy. If a diagnosis of sarcoidosis is confirmed, they will be enrolled and followed. If an alternative diagnosis is made, they will not undergo any further testing. Participants who cannot be classified within the clinical phenotypes based on data from the initial visit will not continue in the study. Recruitment of participants with defined clinical phenotypes will be monitored and ongoing recruitment goals adjusted to achieve overall study objectives.

You may qualify if:

• Age between the ages of 18 and 85.
• Have a diagnosis of sarcoidosis established by consensus criteria (ATS/ERS), confirmed by either biopsy or by manifestations consistent with acute sarcoidosis (Löfgren's syndrome) in absence of other known diagnosis.
• OR Have a suspected diagnosis of sarcoidosis and is scheduled to undergo a biopsy procedure to confirm a diagnosis of sarcoidosis using the same consensus criteria (ATS/ERS).
• Able to tolerate and willing to undergo study procedures.
• Be capable of understanding study forms.
• Provide signed informed consent.

You may not qualify if:

• History of comorbid condition severe enough to significantly increase risks based on investigator discretion.
• Currently an active smoker.
• Undergoing bronchoscopy (clinical or research) with any one of the following:
• severe pulmonary impairment (\<50% predicted FVC, \<1 L FEV1; DLco \<40% predicted, resting hypoxemia \<92% with or without supplemental oxygen)
• other co-morbid disease that would preclude bronchoscopy.
• hypersensitivity to or intolerance of any of the drugs required for sedation during conscious sedation bronchoscopy.
• Known systemic autoimmune disease such as rheumatoid arthritis, lupus, scleroderma, Sjögrens, etc.
• Found to have an alternative interstitial lung disease during evaluation and/or screening.
• Diagnosis of unstable cardiovascular disease including myocardial infarction in the past 6 weeks, uncontrolled congestive heart failure, or uncontrolled arrhythmia
• 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
• Non-Sarcoidosis pulmonary disease (e.g., rheumatoid arthritis, lupus, scleroderma) that, in the opinion of the investigator, limits the interpretability of the analysis of sarcoidosis pulmonary disease
• Primary biliary cirrhosis or autoimmune hepatitis
• Crohn's disease
• Chronic beryllium disease

Sponsors & Collaborators

• University of Pittsburgh: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (9)

Arizona Health Sciences Center

Tucson, Arizona, 85724, United States

Location

University of California - San Francisco

San Francisco, California, 94143, United States

Location

National Jewish Health

Denver, Colorado, 80206, United States

Location

Yale University

New Haven, Connecticut, 06510, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21224, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Medical University of South Caolina

Charleston, South Carolina, 29425, United States

Location

Vanderbilt University

Nashville, Tennessee, 37240, United States

Location

Related Publications (1)

• Ryan SM, Mroz MM, Herzog EL, Ryu C, Fingerlin TE, Maier LA, Gulati M. Occupational and environmental exposures in the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study. Respir Med. 2022 Aug-Sep;200:106923. doi: 10.1016/j.rmed.2022.106923. Epub 2022 Jun 30.

  PMID: 35932543 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Serum, plasma, urine, stool, BAL fluid.

MeSH Terms

Conditions

Sarcoidosis

Condition Hierarchy (Ancestors)

Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Delayed; Hypersensitivity; Immune System Diseases

Study Officials

• Naftali Kaminski, MD

  Yale University

  PRINCIPAL INVESTIGATOR

• Stephen Wisniewski, PhD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

• Michael Becich, MD, PhD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: -Ingelheim Professor of Internal Medicine and Chief of Pulmonary, Critical Care and Sleep Medicine

Study Record Dates

• First Submitted: April 9, 2013
• First Posted: April 15, 2013
• Study Start: May 1, 2013
• Primary Completion: June 1, 2015
• Study Completion: September 1, 2015
• Last Updated: January 12, 2016

Record last verified: 2016-01

Locations

US (9)