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The Pathogenesis and Natural History of Sjogren s Syndrome

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01425892
Recruitment Status : Recruiting
First Posted : August 30, 2011
Last Update Posted : September 12, 2019
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Dental and Craniofacial Research (NIDCR) )

Tracking Information
First Submitted Date August 27, 2011
First Posted Date August 30, 2011
Last Update Posted Date September 12, 2019
Study Start Date August 27, 2011
Primary Completion Date Not Provided
Current Primary Outcome Measures
 (submitted: May 23, 2013)
Clinical phenotyping of SS patients and controls over time; Collection of samples for concurrent and future laboratory studies related to the pathogenesis; Identification of biomarker candidates in SS
Original Primary Outcome Measures Not Provided
Change History Complete list of historical versions of study NCT01425892 on Archive Site
Current Secondary Outcome Measures
 (submitted: August 20, 2014)
  • To establish a teaching cohort of patients with SS or SS-like conditions treated with conventional treatments; To identify patients for other protocols related to Sj(SqrRoot)(Delta)gren's Syndrome
  • To identify patients for other protocols related to Sjogren's Syndrome
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title The Pathogenesis and Natural History of Sjogren s Syndrome
Official Title The Pathogenesis and Natural History of Sjogren s Syndrome
Brief Summary


-Sjogren s syndrome is a disease that affects about 1-4 million Americans. It is more common in women. It mainly affects the glands that produce saliva and tears, leading to dry eyes and dry mouth. The cause of Sjogren s syndrome is unknown, but inflammation plays an important role. The purpose of this study is to learn more about Sjogren s syndrome.


-To better understand how Sjogren s syndrome begins and how it affects patients so that we can develop better ways to treat them.


  • Participants must be 16 years of age or older.
  • They must have a diagnosis of Sjogren s syndrome or have at least two symptoms of Sjogren s syndrome.


  • People taking part in the study will come to the NIH Clinical Center for at least three visits.
  • During these visits, participants will have a medical history and physical exam. They will have oral and dental assessments, and saliva collection. Lab tests (blood and urine) and dry eye exams will be done. Participants will answer questionnaires and have salivary scintigraphy (adults only unless required for diagnosis).
  • Other optional tests may also be done. Participants may have to come in for additional visits if they have these optional tests or if their disease changes.
  • The only treatment provided as part of this study is for medical emergencies or complications that occur while you are at NIH for evaluation.
Detailed Description


Sj(SqrRoot)(Delta)gren s syndrome (SS) is an autoimmune disease characterized by chronic inflammation

involving the exocrine glands. Salivary and lacrimal glands are predominantly affected leading to dry mouth and dry eyes but other exocrine organs are also frequently involved. It is one of the most common rheumatic autoimmune diseases, which effects between 1-4 million Americans, predominantly women with a female to male ratio of 9:1. Sj(SqrRoot)(Delta)gren s syndrome may occur alone (primary SS), or may coexist with other systemic connective tissue disorders (secondary SS). In many cases systemic manifestations, such as fatigue, arthritis, vasculitis, lung disease, peripheral or central neuropathy and autonomic nervous system dysfunction accompany glandular involvement. Patients with systemic manifestations are at higher risk of lymphoma, the incidence of which is increased in SS. The treatment of sicca symptoms is mainly symptomatic, whereas management of extraglandular manifestations is similar to other autoimmune diseases.

The cause and pathogenesis of Sj(SqrRoot)(Delta)gren s syndrome is still largely unknown. In a genetically predisposed individual various environmental factors, such as viral infections, may lead to epithelial cell activation and a protracted inflammatory response with features of autoimmunity. Autoreactive lymphocytes and autoantibodies are considered important in this process although the pathogenic role of any particular autoantibody is still undefined. Although inflammation may contribute to the exocrinopathy of SS, the relationship between inflammation and exocrine dysfunction is poorly understood. Moreover, the model does not explain many of the extraglandular manifestations of SS patients, such as fatigue. Further studies are needed to better understand the pathogenesis of SS.


The primary objective of this study is to enable the collection of longitudinal clinical and laboratory data and biologic specimens to identify pathogenetic mechanisms of SS by careful clinical phenotyping of SS patients and Sj(SqrRoot)(Delta)gren s-like conditions over time and collection of biologic samples for concurrent and future laboratory studies related to the pathogenesis of Sj(SqrRoot)(Delta)gren s syndrome. Another objective of the study is to identify biomarker candidates associated with the diagnosis, severity, prognosis, or organ involvement in SS.

The protocol will enable the study of the genetic basis and the mechanistic aspects of immunologic and non-immunologic abnormalities of SS and their associations with various clinical phenotypes.


The study will enroll 300 subjects with Sj(SqrRoot)(Delta)gren s syndrome or Sj(SqrRoot)(Delta)gren s-like conditions. Subjects aged 16- years or older fulfilling European American Consensus Criteria for Primary or Secondary Sj(SqrRoot)(Delta)gren s syndrome are eligible for the study. Selected subjects with incomplete Sj(SqrRoot)(Delta)gren s syndrome or who are excluded from the European American criteria may also be eligible. Screening will be done on the Characterization of Diseases with Salivary Gland Involvement protocol (15-D-0051) prospectively or on the previous screening protocol (84-D-0056).


This is a longitudinal observational study. All subjects will have at least three core evaluations (approximately biannually) during a 4-5 year period. Additional evaluations may be required if there is a significant change in the clinical condition of subjects likely related to SS or sicca syndrome or to provide additional research samples or clinical data for the pathogenesis studies. Clinical data will be collected through questionnaires, personal interviews, physical examination, laboratory testing and imaging studies. The core evaluation will include a complete medical history and physical examination and a complete oral and dry eye evaluation. Research studies include salivary scintigraphy for functional assessment of salivary gland function, testing of the autonomous nervous system and may include an ultrasound guided parotid core needle biopsy. Blood, saliva and biopsy samples will be stored and used for laboratory research studies aimed at the pathogenesis of Sj(SqrRoot)(Delta)gren s syndrome. Samples labeled with a code without any personal identifiers may be shared with researchers in and outside the NIH. DNA will be collected for genetic studies related to Sj(SqrRoot)(Delta)gren s syndrome and related conditions.

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Not Provided
Study Population Not Provided
  • Pathogenesis
  • Sjogren's Syndrome
  • Salivary Gland
Intervention Not Provided
Study Groups/Cohorts Not Provided
Publications *

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: August 27, 2011)
Original Estimated Enrollment Same as current
Study Completion Date Not Provided
Primary Completion Date Not Provided
Eligibility Criteria

    1. Ability to sign informed consent form
    2. Fulfilling one the definitions below:

      1. Sj(SqrRoot)(Delta)gren s defined by European-American (EA) classification criteria for primary or secondary Sj(SqrRoot)(Delta)gren s syndrome (SS group)
      2. Excluded from the EA criteria because of a comorbid condition but otherwise fulfilling the European-American classification criteria (EA excluded SS group)
      3. Incomplete SS

      i. at least 2 of the EA criteria with a common manifestation of SS not included in these criteria (e.g., fatigue, vasculitis, arthritis, etc)

      ii. 2 or more common manifestations of SS which are not included in the EA criteria (e.g.,: fatigue, vasculitis, arthritis, autonomic dysfunction, etc ) and are not explained by other conditions


    1. Age <16 years
    2. inability or unwillingness to comply with follow up requirements
    3. Any medical or psychological/psychiatric condition or treatment that, in the opinion of the Principal Investigator, would exclude the subjects from the research studies (e.g., alternative explanation for subjects signs and symptoms)
    4. NIH employees who report directly to the principal investigator or who are a co-worker or relative of the principal investigator..
Sexes Eligible for Study: All
Ages 16 Years to 70 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers No
Contact: Eileen M Pelayo (301) 594-3097
Contact: Blake M Warner, D.D.S. (301) 496-4486
Listed Location Countries United States
Removed Location Countries  
Administrative Information
NCT Number NCT01425892
Other Study ID Numbers 110172
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party National Institutes of Health Clinical Center (CC) ( National Institute of Dental and Craniofacial Research (NIDCR) )
Study Sponsor National Institute of Dental and Craniofacial Research (NIDCR)
Collaborators Not Provided
Principal Investigator: Blake M Warner, D.D.S. National Institute of Dental and Craniofacial Research (NIDCR)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date June 4, 2019