Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials
Trial record 1 of 5 for:    11-E-0072
Previous Study | Return to List | Next Study

Environmental Risk Factors for the Anti-synthetase Syndrome

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by National Institutes of Health Clinical Center (CC)
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Environmental Health Sciences (NIEHS) ) Identifier:
First received: January 12, 2011
Last updated: November 11, 2014
Last verified: March 2014


  • 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.


- 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.


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


  • 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.


Study Type: Observational
Official Title: Environmental Risk Factors for the Anti-Synthetase Syndrome

Resource links provided by NLM:

Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 450
Study Start Date: January 2011
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.


Ages Eligible for Study:   2 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes

There are no gender, ethnic or age restrictions 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 at leas t two years of age .
  4. Able and willing to give informed consent, to complete the questionnaires and to donate blood samples (in case of children at least 2 years of age but < 18 years of age , parent/legal guardian must be willing and able to provide informed consent and child must provide assent).

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), gender- and age- (within 5 years for minors and within 10 years for adults) matched, who is living as close as possible to the geographic area of the myositis patient.
  2. Controls should be without a recognized autoimmune disease or ILD.
  3. Able and willing to give informed consent, to complete the questionnaires and to donate blood samples (in case of children 2 years of age but < 18 years of age, parent/legal guardian must be willing and able to provide informed consent) and child must provide assent).


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 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 .
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01276470

Contact: Tasia Long, MHS (301) 451-6031
Contact: Frederick W Miller, M.D. (301) 451-6273

United States, Florida
University of Miami Recruiting
Miami, Florida, United States, 33101
United States, Maryland
Johns Hopkins University Recruiting
Baltimore, Maryland, United States, 21205
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010   
Mid-Atlantic Kaiser Permanente- Recruiting
Rockville, Maryland, United States
United States, Massachusetts
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
United States, Minnesota
Mayo Clinic, Rochester Recruiting
Rochester, Minnesota, United States, 55905
United States, North Carolina
NIEHS Clinical Research Unit (CRU) Recruiting
Research Triangle Park, North Carolina, United States
United States, Pennsylvania
University of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15261
Sponsors and Collaborators
Principal Investigator: Frederick W Miller, M.D. National Institute of Environmental Health Sciences (NIEHS)
  More Information

Additional Information:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Environmental Health Sciences (NIEHS) ) Identifier: NCT01276470     History of Changes
Other Study ID Numbers: 110072, 11-E-0072
Study First Received: January 12, 2011
Last Updated: November 11, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Adult and Pediatric Autoimmune Disease
Autoimmune Diseases
Autoimmunity Pathogenesis
Environmental Risk Factors

Additional relevant MeSH terms:
Muscular Diseases
Musculoskeletal Diseases
Nervous System Diseases
Neuromuscular Diseases processed this record on November 25, 2014