Environmental Risk Factors for the Anti-synthetase Syndrome

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	Yes
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Observational
Eligible Ages	2 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

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INCLUSION CRITERIA:
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 grester than 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, 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 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 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).

EXCLUSION CRITERIA:

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 . 5. Patients who at their reference date were not in the US or Canada. 6. 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.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT01276470
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	National Institute of Environmental Health Sciences (NIEHS)
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Adam I Schiffenbauer, M.D.
Principal Investigator Affiliation	National Institute of Environmental Health Sciences (NIEHS)
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	NIH
Overall Status	Recruiting
Countries	United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Myositis, Dermatomyositis, Polymyositis, Juvenile Dermatomyositis, Juvenile Polymyositis
Study Website:	View Trial Website

Additional Details

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.

Arms & Interventions

Arms

: Antisynthetase Negative

Subjects with myositis without antisynthetase syndrome

: Antisynthetase Positive

Subject with myositis with antisynthetase syndrome

: Healthy Control

Subjects without autoimmune disease

Interventions

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

University of Miami Hospital, Miami, Florida

Status

Withdrawn

Address

University of Miami Hospital

Miami, Florida, 33101

Site Contact

[email protected]

(301) 451-6270

Johns Hopkins University, Baltimore, Maryland

Status

Completed