SarcoidosisGRADS SarcNCT01831739

Genomic Research in Sarcoidosis

An observational study of Sarcoidosis, run by University of Pittsburgh at 9 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial 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. Read more about this study

Who is it for?: Ages 18 to 85 years
Conditions the study is for: Sarcoidosis
Type of treatment: Injection or infusion
How many people: 368 participants
Where: 9 sitesUnited States
Study dates: May 2013to Sep 2015
Phase: Observational
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 85 years
All sexes
No healthy volunteers
Adult, Older adult

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.

Who may be able to join

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.

Who cannot join

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.

Show all 31Show fewer

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
Have an active bacterial or viral infection at time of screening.
Have an active or ongoing serious infection, including HIV, HBV and HCV
Active tuberculosis or are taking any medication for tuberculosis
Have a history of demyelinating diseases, lymphoproliferative diseases, or other malignancies other than presumed cured non-metastatic skin cancer
Have evidence of a likely malignancy on chest x-ray
Are currently pregnant at time of screening
Currently institutionalized (e.g., prisons, long-term care facilities)
Hypersensitivity to or intolerance of albuterol sulfate or propellants or excipients of the inhalers
History of Lung volume reduction surgery, lung resection or bronchoscopic lung volume reduction in any form.
History of lung or other organ transplant
Unable to comprehend consent document and/or questionnaires
Conditional Exclusions:
Participants who present with an upper respiratory infection or pulmonary exacerbation, either solely participant-identified or that has been clinically treated, in the last four weeks can be rescreened for the study once the four-week window has closed.
Participants who present with current use of acute antibiotics or have acute antibiotics within the past four weeks can be rescreened for the study ≥28 days after discontinuing acute antibiotics.
Female participants who present <3 months after giving birth will be asked to reschedule their visit until three months have passed since the birth.
Former smoker who quit < 3months prior to enrollment

Trial locations and contacts

9 sites in 1 country.

City, postcode or hospital

9 sites in 1 country

United States9 sites

Johns Hopkins University
Baltimore, Maryland, 21224
Medical University of South Caolina
Charleston, South Carolina, 29425
National Jewish Health
Denver, Colorado, 80206
Vanderbilt University
Nashville, Tennessee, 37240
Yale University
New Haven, Connecticut, 06510
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
University of California - San Francisco
San Francisco, California, 94143
Arizona Health Sciences Center
Tucson, Arizona, 85724

Other trials in United States

About this study

Official title: Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) - Sarcoidosis Protocol

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:

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

Read the detailed description

Sarcoidosis is a systemic disease characterized by the formation of granulomatous lesions, especially in the lungs, liver, skin, and lymph nodes, with a heterogeneous set of clinical manifestations and a variable course 1. Despite significant progress in the understanding of the genetic predisposition and role of immunity, it is still a challenge to explain the clinical presentation of sarcoidosis. Standard clinical assessment, imaging, and pulmonary function tests (PFTs) do not allow prediction of disease course and response to therapy. Furthermore, there are no good long-term therapies. Considering that the interactions between potential infections, changes in systemic inflammation, and patterns in lung microbiome and the different and distinct disease phenotypes in sarcoidosis are not well understood, the Sarcoidosis protocol for the Genomic Research in AAT Deficiency and Sarcoidosis (GRADS) grant (hereafter called GRADS Sarcoidosis protocol) 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.

Specific Aims

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

Focusing on accessible PBMCs should enable GRADS researchers to identify markers for disease phenotypes, severity, and outcome. Analysis of lesional transcriptomes (mRNA, microRNA and lincRNA) will add mechanistic insights. High throughput unbiased analysis of the lung microbiome will potentially identify patterns in the lung microbiome that determine disease activity and persistence, as well as response to therapy.

Participants are assigned a provisional clinical phenotype upon obtaining consent at time of enrollment by the respective recruiting center. Clinical phenotypes will be reviewed, confirmed, and monitored to ensure achievement of study objectives. Participants who cannot be assigned a clinical phenotype after the initial study visit will be excluded from additional study participation.

Conditions: Sarcoidosis
Keywords: Genomics, Microbiome, Microflora, Virome
Medical subject headings: Sarcoidosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT01831739
Study group	Role	What they receive
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.

What is being measured

The primary outcome is the main question the study is designed to answer.

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).
Measured: Baseline, 6 months, 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2013Sep 2015

First posted15 Apr 2013 (estimated)
Study startMay 2013
Primary completionJun 2015
Study completionSep 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for SarcoidosisStudies of the same condition, open and under way.
More trials run by University of PittsburghThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Observational
Observational model: Cohort
Time perspective: Prospective
Enrolment: 368 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01831739
Sponsor's protocol ID: 13020130
Other IDs: U01HL112707
Acronym: GRADS Sarc
Status last verified: Jan 2016
First submitted: 9 Apr 2013
Last updated: 12 Jan 2016
Results posted: No
Data monitoring committee: Yes

Publications

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.
PubMed 35932543

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingObservational study
Role of Genetic Factors in the Development of Lung Disease
Cystic Fibrosis, Pulmonary Fibrosis
Not yet recruitingPhase 2
LAM-001 for the Treatment of Sarcoidosis Associated Pulmonary Hypertension (SAPH)
Sarcoidosis Associated Pulmonary Hypertension
RecruitingPhase 2/3
A Study of Brepocitinib in Adults With Cutaneous Sarcoidosis
Cutaneous Sarcoidosis
Not yet recruitingPhase 2
An Efficacy Study of XTMAB-16 in Patients With Pulmonary Sarcoidosis With or Without Extrapulmonary Manifestations
Pulmonary Sarcoidosis
RecruitingObservational study
Prognostic Value of Clinical Cardiovascular MRI
Sarcoidosis

All Sarcoidosis trials

Study at a glance

From the registry record, last updated by the sponsor on 12 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) - Sarcoidosis Protocol
ClinicalTrials.gov ID: NCT01831739
Acronym / sponsor ID: GRADS Sarc / 13020130
Conditions: Sarcoidosis
Keywords: Genomics, Microbiome, Microflora, Virome
Study type: Observational
Recruitment status: Completed
Enrolment: 368 participants (actual)
Lead sponsor: University of PittsburghUniversity, hospital or other
Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
Study start: May 2013
Primary completion: Jun 2015 (actual)
Study completion: Sep 2015 (actual)
First posted: 15 Apr 2013 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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:

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

Detailed description

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.

Specific Aims

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

Study design

Observational model: Cohort
Time perspective: Prospective
Number of arms: 9

Arm	Type	Receives
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.

Who may qualify

Ages: 18 to 85 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult
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.

Key inclusion criteria (6 listed)

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.

Key exclusion criteria (31 listed)

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:
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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Primary outcome

PBMC Gene Expression
Time frame: Baseline, 6 months, 12 months
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).

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2016.
Derived from this study: PubMed 35932543Ryan 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.

Related trials for Sarcoidosis

RecruitingObservational study
Role of Genetic Factors in the Development of Lung Disease
Cystic Fibrosis, Pulmonary Fibrosis
Not yet recruitingPhase 2
LAM-001 for the Treatment of Sarcoidosis Associated Pulmonary Hypertension (SAPH)
Sarcoidosis Associated Pulmonary Hypertension
RecruitingPhase 2/3
A Study of Brepocitinib in Adults With Cutaneous Sarcoidosis
Cutaneous Sarcoidosis
Not yet recruitingPhase 2
An Efficacy Study of XTMAB-16 in Patients With Pulmonary Sarcoidosis With or Without Extrapulmonary Manifestations
Pulmonary Sarcoidosis
RecruitingObservational study
Prognostic Value of Clinical Cardiovascular MRI
Sarcoidosis

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Naftali Kaminski, MD principal investigator

Yale University

Stephen Wisniewski, PhD principal investigator

University of Pittsburgh

Michael Becich, MD, PhD principal investigator

University of Pittsburgh

9 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

An observational study of Sarcoidosis, run by University of Pittsburgh at 9 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

PBMC Gene Expression (time frame: Baseline, 6 months, 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01831739, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jan 2016.