ClinicalTrials.gg
Sign In
RecruitingNCT01276470Updated Oct 16, 2026

Environmental Risk Factors for the Anti-synthetase Syndrome

An observational study in Myositis, Dermatomyositis and Polymyositis, sponsored by National Institute of Environmental Health Sciences (NIEHS). Recruiting at 8 sites in United States. Open to participants aged 2 Years to 100 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-10-16.

Primary conditionDermatomyositisRegistry: MyositisReclassifiedWhy we changed it
Registry
Myositis — the first condition term the registry derived for this study.
ClinicalTrials.gg
Dermatomyositis
Why
  1. The study's listed conditions name Dermatomyositis, a narrower term within Myositis.
Confidence
High: the new condition is named in the study's own listed conditions. Of 351 hand-checked studies reclassified this way, 68% were exactly right and 84% in the right disease family; the registry's first term was right for 5% (measured 2026-10-21). How we classify →
Wrong?
Tell us the study's main condition →

Sponsored by National Institute of Environmental Health Sciences (NIEHS) · Observational

From the registry’s dates

  • Started Feb 2011; still recruiting 15 years 9 months later.
Study type
Observational
Model
Case-control
Time perspective
Cross-sectional
Enrollment
580
Ages
2 Years to 100 Years
Sex
All
01

Study summary

Background:

  • Like other complex diseases, autoimmune diseases are the result of numerous causes, including genetic and environmental factors. Some researchers believe that people who are susceptible to autoimmune disorders develop them when the body reacts to environmental or other factors by creating white blood cells that attack the body s own tissues, which then progresses to autoimmune diseases. These immune-triggered disorders can overlap with one another to some extent, but most autoimmune diseases have certain distinct triggers.
  • The autoimmune disorder myositis weakens the muscles and may cause other health problems. Environmental exposures associated with myositis include ultraviolet radiation, stressful life events and muscle overexertion, collagen implants, infections such as retroviruses and streptococci bacteria, and certain drugs and chemicals. Some individuals with myositis also produce proteins in the blood called autoantibodies that react with certain parts of the person s own cells, called synthetases, which are involved in making new proteins. A syndrome called the anti-synthetase syndrome, which includes myositis and lung disease, is associated with having the anti-synthetase autoantibodies. Researchers are interested in studying differences in environmental exposures in individuals with myositis. This study is being conducted to determine if persons with the anti-synthetase syndrome have had different environmental exposures before disease onset compared with other patients with myositis who do not have this syndrome and also compared with healthy volunteers.

Objectives:

- To determine whether selected infectious and noninfectious environmental exposures are more common in individuals who have myositis with the anti-synthetase syndrome, compared with healthy volunteers.

Eligibility:

- Individuals who have been diagnosed with myositis (with or without anti-synthetase autoantibodies), and healthy volunteers without autoimmune disorders.

Design:

  • Participants will be screened with a full medical history and physical examination, and will provide blood, urine and house dust samples.
  • Participants will complete questionnaires about their medical history and the types of exposures they have had at work, at home, and elsewhere. Participants who have myositis will also be asked about certain infections, heavy exercise or physical exertion, sun exposure, tobacco and alcohol use, and stressful events prior to being diagnosed with the disease. Healthy volunteers will be asked about the same exposures before the date of diagnosis of disease of the myositis subject to which they have been matched.
  • Participants will receive a kit that contains instructions and a filter to be put onto their vacuum cleaner to collect house dust in the bedroom. This dust will be kept for possible future analyses of infectious or toxic agents based on the other results from the study.
  • Individuals with myositis will have other tests as clinically indicated, including lung function tests and imaging studies.
Read the detailed description

Most autoimmune diseases are thought to develop as a result of chronic immune activation and dysregulation after selected environmental exposures in genetically susceptible individuals. Based on prior studies suggesting roles for noninfectious and infectious agents in the development of myositis, as well as the known clinical, epidemiologic and genetic differences among phenotypes, we hypothesize that different myositis phenotypes are triggered by different environmental exposures in genetically susceptible individuals. One phenotype that is particularly well-defined clinically and genetically, and for which environmental triggers are likely, is myositis associated with anti-synthetase autoantibodies (defined as the anti-synthetase syndrome). These patients have an acute myositis onset in the spring of the year and also tend to develop fevers, elevated white blood cell counts, arthritis and interstitial lung disease. Although these features are consistent with an environmental trigger for the anti-synthetase syndrome, and although case reports and animal models suggest infectious or noninfectious agents may play a role, no study has systematically assessed environmental agents in this population.

In collaboration with multiple centers, we plan to test the hypothesis that certain environmental exposures are associated with the anti-synthetase syndrome and differ from those seen in matched controls and in myositis patients without the anti-synthetase syndrome. The specific aims of this study are to: 1) determine whether selected noninfectious environmental exposures are more common preceding disease onset in 150 recent-onset (defined as within 24 months of meeting criteria for possible, probable or definite myositis) myositis patients with the anti-synthetase syndrome, compared with 150 control subjects without autoimmune disease (1:1 matched with the patients), and compared with 150 recent-onset myositis patients without the anti-synthetase syndrome; and 2) determine whether selected infectious agents can be detected more frequently in blood samples of recent-onset anti-synthetase syndrome patients compared with matched controls, and in blood or biopsy samples from recent-onset anti-synthetase myositis patients compared with recent-onset myositis patients without the anti-synthetase syndrome.

Medical histories, concurrent conditions and environmental questionnaire information will be collected from all participants. Subjects will undergo a clinical, laboratory and immunologic assessment to document current diagnoses, disease manifestations and severity. A chest x-ray, high resolution computed tomography (HRCT) of the chest, pulmonary function tests, bronchoalveolar lavage, and muscle and lung biopsies will be performed as clinically indicated. Blood DNA and RNA sera, biopsy and house dust repositories will be created for current and future investigations.

02

Conditions studied

  • Myositis
  • Dermatomyositis
  • Polymyositis
  • Juvenile Dermatomyositis
  • Juvenile Polymyositis

Browse trials for

Keywords

  • Adult and Pediatric Autoimmune Disease
  • Antibody
  • Autoimmune Diseases
  • Autoimmunity Pathogenesis
  • Environmental Risk Factors
  • Natural History
03

In context

Dermatomyositis Reclassified

184 studies on the registry are indexed under Dermatomyositis; 63 are open to participants now.

This study's planned enrollment of 580 is above the median of 179 across 45 observational studies indexed under Dermatomyositis.

Browse Dermatomyositis studies →

Lead sponsor

National Institute of Environmental Health Sciences (NIEHS) is the lead sponsor of 183 studies on the registry; 18 are open to participants now.

Browse National Institute of Environmental Health Sciences (NIEHS) studies →

Compared within Dermatomyositis, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Myositis. The counts are of registry records indexed under each term, refreshed daily. How we classify →

04

Who can participate

Ages eligible
2 Years to 100 Years
Sexes eligible
All
Accepts healthy volunteers
Yes
Sampling method
Probability sample

Study population

General population; There are no gender or ethnic restrictions to enrollment in the study. Age restrictions for children do apply to enrollment in the study.@@@@@@

Eligibility criteria

  • INCLUSION CRITERIA:

There are no gender or ethnic restrictions to enrollment in the study. Age restrictions for children do apply to enrollment in the study.

The inclusion criteria for enrollment of myositis subjects are:

  1. Diagnosis of myositis based on criteria for possible, probable or definite PM or DM, with or without other connective tissue diseases, documented within 24 months of enrollment (using the most recent diagnosis date to define the 24-month period).
  2. CXR to assess possible ILD and assign the subject to the presumptive anti-synthetase positive or negative category if clinically indicated.
  3. Children must be greater than two years of age.
  4. Able and willing to give , to complete the questionnaires and to donate blood samples (in case of children greater than 2 years of age but \<18 years of age, parent/legal guardian must be willing and able to provide informed consent and child will provide assent according to child s maturity level and understanding).

The exclusion criteria for myositis subjects are:

  1. Cancer-associated myositis (cancer diagnosed within 2 years of the diagnosis of myositis).
  2. Inclusion body myositis.
  3. Myositis that has clearly developed as the result of a drug, toxin or other exposure and has resolved after discontinuation of the exposure to that agent.
  4. Children less than 2 years of age.

The inclusion criteria for controls are:

  1. Friends or, if friends are not available, cousins of the anti-synthetase-positive myositis patient, or, if friends or cousins are not available, volunteers from the general community (such as the NIH Normal volunteer program), race- gender- and age- (within 5 years for minors and within 10 years for adults) matched, and when possible who is living as close as possible to the geographic area of the myositis patient.
  2. Controls should be without a recognized disease or ILD.
  3. Able and willing to give informed consent, to complete the questionnaires and to donate blood samples (in case of children greater than 2 years of age but \<18 years of age, parent/legal guardian must be willing and able to provide informed consent) and child will provide assent according to child maturity level and understanding).

The exclusion criteria for all protocol subjects are:

  1. Medical illness that in the judgment of the investigators does not allow safe blood draws or other clinical evaluations needed for study participation.
  2. Cognitive impairment.
  3. Not able or willing to give informed assent or consent.
  4. Children less than 2 years of age.
  5. Patients who at their reference date were not in the US or Canada
  6. Individuals currently incarcerated

considerations:

HIV is not an exclusion for affected participants in this study for the two following reasons:

  1. It has no impact on study procedures or tests.
  2. It may be one of the viral risk factors we are investigating.
Terms in these criteria, in plain language(3)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Autoimmune disease

A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.

Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

05

Study design

Observational model
Case-control
Time perspective
Cross-sectional
Enrollment
580 participants (estimated)

Groups and cohorts

  • Antisynthetase Negative

    Subjects with myositis without antisynthetase syndrome

  • Antisynthetase Positive

    Subject with myositis with antisynthetase syndrome

  • Healthy Control

    Subjects without autoimmune disease

06

What researchers measure

Primary outcomes

  1. To determine whether selected noninfectious environmental exposures are more common prior to disease in recent-onset pts. w/anti-sythetase syndrome compared w/controls w/o autoimmune disease (1:1 matched with the pts.) and compared w/recent-onse...

    Environmental Questionnaire (EQ) and Child Environmental Questionnaire (CQ)

    Time frame: Enrollment

07

Study locations

2 of 8 sites recruiting
08

References and documents

Publications

  • Sherman MA, Yang Q, Gutierrez-Alamillo L, Pak K, Flegel WA, Mammen AL, Rider LG, Casciola-Rosen LA; Childhood Myositis Heterogeneity Collaborative Study Group. Clinical Features and Immunogenetic Risk Factors Associated With Additional Autoantibodies in Anti-Transcriptional Intermediary Factor 1gamma Juvenile-Onset Dermatomyositis. Arthritis Rheumatol. 2024 Apr;76(4):631-637. doi: 10.1002/art.42768. Epub 2024 Jan 30. PubMed 38059274 ↗
09

Updates

4 registry updates since Sep 25, 2026
Minor edits
Nothing that changes what the study is or who can join. Edited: description
4 updates, last Oct 16, 2026
Show all 4 updates
  1. Oct 16, 2026
    Minor edits only
    + 1 other change: description
  2. Oct 13, 2026
    Minor edits only
    + 1 other change: description
  3. Oct 8, 2026
    Minor edits only
    + 1 other change: description
  4. Sep 28, 2026
    Minor edits only
    + 1 other change: description

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

10

Registry details

Key details

Study ID
NCT01276470
Lead sponsor
National Institute of Environmental Health Sciences (NIEHS)
Responsible party
Sponsor
First posted
Jan 13, 2011
Start date
Feb 9, 2011
Last update
Oct 16, 2026

Study contacts

Adam I Schiffenbauer, M.D.
Contact
schiffenbauera2@mail.nih.gov
(301) 451-6270
Adam I Schiffenbauer, M.D.
principal investigator · National Institute of Environmental Health Sciences (NIEHS)

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Interested in this study?

Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.

Contact study team

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Dermatomyositis →

Other studies from this sponsor

National Institute of Environmental Health Sciences (NIEHS) →

Start the discussion