MyositisNCT01276470
Environmental Risk Factors for the Anti-synthetase Syndrome
An observational study of Myositis and Dermatomyositis, run by National Institute of Environmental Health Sciences (NIEHS) at 8 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 2 to 100 yearsHealthy volunteers can take part
- Conditions the study is for
- Myositis, Dermatomyositis, Polymyositis
- How many people
- 580 participants
- Where
- 8 sitesUnited States
- Study dates
- 9 Feb 2011to not given
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 2 to 100 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
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.@@@@@@
Who may be able to join
- 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:
- 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).
- CXR to assess possible ILD and assign the subject to the presumptive anti-synthetase positive or negative category if clinically indicated.
- Children must be greater than two years of age.
- 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 s maturity level and understanding).
Show all 26Show fewer
- The exclusion criteria for myositis subjects are:
- Cancer-associated myositis (cancer diagnosed within 2 years of the diagnosis of myositis).
- Inclusion body myositis.
- 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.
- Children less than 2 years of age.
- The inclusion criteria for controls are:
- 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.
- Controls should be without a recognized autoimmune disease or ILD.
- 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:
- Medical illness that in the judgment of the investigators does not allow safe blood draws or other clinical evaluations needed for study participation.
- Cognitive impairment.
- Not able or willing to give informed assent or consent.
- Children less than 2 years of age.
- Patients who at their reference date were not in the US or Canada
- Individuals currently incarcerated
- HIV considerations:
- HIV is not an exclusion for affected participants in this study for the two following reasons:
- It has no impact on study procedures or tests.
- It may be one of the viral risk factors we are investigating.
Who cannot join
None listed.
Trial locations and contacts
8 sites in 1 country. Contact the study team or a site near you to ask about taking part.
8 sites in 1 country
United States8 sites, 2 recruiting
- Completed
Johns Hopkins University
Baltimore, Maryland, 21205
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
NIH Clinical Center Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY dial 711, ccopr@nih.gov
- Completed
Brigham and Women's Hospital
Boston, Massachusetts, 02115
- Withdrawn
University of Miami Hospital
Miami, Florida, 33101
- Completed
University of Pittsburgh
Pittsburgh, Pennsylvania, 15261
- Recruiting
NIEHS Clinical Research Unit (CRU)
Research Triangle Park, North Carolina, 27709
Adam Schiffenbauer, M.D., 301-451-6270, schiffenbauera2@mail.nih.gov
- Completed
Mayo Clinic, Rochester
Rochester, Minnesota, 55905
- Completed
Mid-Atlantic Kaiser Permanente
Rockville, Maryland, 20853
About this study
Official title: Environmental Risk Factors for the Anti-Synthetase Syndrome
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.
Read more
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.
- Keywords
- Adult and Pediatric Autoimmune Disease, Antibody, Autoimmune Diseases, Autoimmunity Pathogenesis, Environmental Risk Factors, Natural History
- Medical subject headings
- Myositis, Dermatomyositis, Polymyositis, Autoimmune Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Antisynthetase Negative | Subjects with myositis without antisynthetase syndrome | |
| Antisynthetase Positive | Subject with myositis with antisynthetase syndrome | |
| Healthy Control | Subjects without autoimmune disease |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: Enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2011 (estimated)
- Study start9 Feb 2011
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 MyositisStudies of the same condition, open and under way.
- 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
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 580 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Institute of Environmental Health Sciences (NIEHS)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Adam I Schiffenbauer, M.D., Principal investigator, National Institute of Environmental Health Sciences (NIEHS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01276470
- Sponsor's protocol ID
- 110072
- Other IDs
- 11-E-0072
- Status last verified
- 17 Sep 2026
- First submitted
- 12 Jan 2011
- Last updated
- 16 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
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
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Environmental Risk Factors for the Anti-Synthetase Syndrome
- ClinicalTrials.gov ID
- NCT01276470
- Acronym / sponsor ID
- 110072
- Keywords
- Adult and Pediatric Autoimmune Disease, Antibody, Autoimmune Diseases, Autoimmunity Pathogenesis, Environmental Risk Factors, Natural History
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 580 participants (estimated)
- Lead sponsor
- National Institute of Environmental Health Sciences (NIEHS)US National Institutes of Health
- Study start
- 9 Feb 2011 (actual)
- First posted
- 13 Jan 2011 (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.
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.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Antisynthetase Negative | – | –Subjects with myositis without antisynthetase syndrome |
| Antisynthetase Positive | – | –Subject with myositis with antisynthetase syndrome |
| Healthy Control | – | –Subjects without autoimmune disease |
Who may qualify
- Ages
- 2 to 100 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- 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.@@@@@@
Key inclusion criteria (26 listed)
- There are no gender or ethnic restrictions to enrollment in the study. Age restrictions for children do apply to enrollment in the study.
- 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).
- CXR to assess possible ILD and assign the subject to the presumptive anti-synthetase positive or negative category if clinically indicated.
- Children must be greater than two years of age.
- 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 s maturity level and understanding).
Key exclusion criteria (0 listed)
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
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...
Time frame: Enrollment
Environmental Questionnaire (EQ) and Child Environmental Questionnaire (CQ)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2026.
- Derived from this study: PubMed 38059274Sherman 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.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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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.
Adam I Schiffenbauer, M.D. principal investigator
National Institute of Environmental Health Sciences (NIEHS)
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Myositis and Dermatomyositis, run by National Institute of Environmental Health Sciences (NIEHS) at 8 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 26 inclusion and 0 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: looking for participants now, as of the sponsor's last update on 16 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Adam I Schiffenbauer, M.D. ((301) 451-6270, schiffenbauera2@mail.nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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... (time frame: Enrollment). 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 NCT01276470, 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 16 Oct 2026.