ClinicalTrials.gov
ClinicalTrials.gov Menu

Biomarkers in Primary Sjögren's Syndrome (pSS)

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.
ClinicalTrials.gov Identifier: NCT03765593
Recruitment Status : Not yet recruiting
First Posted : December 5, 2018
Last Update Posted : December 5, 2018
Sponsor:
Information provided by (Responsible Party):
Maria Soledad Retamozo, National Council of Scientific and Technical Research, Argentina

Brief Summary:

The clinical spectrum of primary Sjogren Syndrome (pSS)ranges from sicca syndrome to systemic involvement (extraglandular manifestations), including a large number of manifestations that may be the form of presentation or appear after the disease is diagnosed, and that clearly mark the prognosis of the disease.

Gene expression levels of Interferon (INF) and B Lymphocyte Biomarkers as Markers of Systemic Affectation and Lymphoproliferative Disease in, together with clinical and laboratory parameters, will provide significant information about the risk of developing hematological neoplasms in patients with pSS at different stages of the disease, and lead to better management of the disease treatment and therapeutic behaviors.

Using the proposed technique allows us to study the gene expression at the mRNA level of each biomarker, which allows us to anticipate the irreversible changes that take place due to the progress of the pathology in progress, since the molecular changes precede the histological changes and in the pathological diagnosis.


Condition or disease Intervention/treatment
Primary Sjögren Syndrome Lymphoma, Non-Hodgkin Procedure: Biopsy Salivary Gland

Detailed Description:

This project, address the value of these proposed biomarkers in pSS with regard to disease activity and risk stratification of pSS subsets. The investigator's group aim to determine if the proposed biomarkers and their gene expression in saliva, peripheral blood and minor salivary gland samples in patients with pSS are increased to know the degree of their usefulness in daily clinical practice, to indicate which patients have a highest risk of developing a hematological malignancy and to know if these biomarkers are useful to recognize patients who have greater activity of the disease to be able to use it in the follow-up of the disease and as a future responder of the new biological therapies against B cells, INF and monocytes.

Gene expression is a highly regulated mechanism that controls the function and adaptability of all living cells. The field of gene expression analysis has undergone important advances in biomedical research. Today, quantification techniques of mRNA expression have led to improvements in the identification of the gene and the sub-classification of the disease, for example, the expression of specific genes (mRNA) can be quantified by reverse transcription and PCR in quantitative real time. This is the most sensitive technique available to detect and quantify mRNA, where extremely small sample sizes can be used in mRNA quantification. Molecular changes precede histological changes and clinicians in the diagnosis of a pathology. For this reason, studying gene expression at the mRNA level allows us to anticipate irreversible changes that take place due to the progress of the pathology in progress.


Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Gene Expression of Interferon (INF) and B Lymphocyte Biomarkers as Markers of Systemic Affectation and Lymphoproliferative Disease in Primary Sjögren's Syndrome
Estimated Study Start Date : March 2019
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : March 2021


Group/Cohort Intervention/treatment
Study group 1
Immunopositive primary SS (Anti-SSA +/anti-Ro+) will receive salivary gland biopsy.
Procedure: Biopsy Salivary Gland
A minor salivary gland biopsy will be performed at lower lip, with the minimally invasive technique that is carried out in Rheumatology Unit as a routine procedure for the diagnosis of pSS, from there it will be taken between 2-3 glands for the study. RNAlater®(Ambion, Inc., Texas, United States of America) will be stored in solution for the stabilization and preservation of RNA at -80ºC.

Study group 2
Immunonegative primary SS (Anti-SSA -/anti Ro-, biopsy Chisholm-Mason 3-4) will receive salivary gland biopsy.
Procedure: Biopsy Salivary Gland
A minor salivary gland biopsy will be performed at lower lip, with the minimally invasive technique that is carried out in Rheumatology Unit as a routine procedure for the diagnosis of pSS, from there it will be taken between 2-3 glands for the study. RNAlater®(Ambion, Inc., Texas, United States of America) will be stored in solution for the stabilization and preservation of RNA at -80ºC.

Study group 3
Non-autoimmune sicca syndrome (Anti-SSA/anti Ro-, biopsy Chisholm-Mason 2 o less) will receive salivary gland biopsy.
Procedure: Biopsy Salivary Gland
A minor salivary gland biopsy will be performed at lower lip, with the minimally invasive technique that is carried out in Rheumatology Unit as a routine procedure for the diagnosis of pSS, from there it will be taken between 2-3 glands for the study. RNAlater®(Ambion, Inc., Texas, United States of America) will be stored in solution for the stabilization and preservation of RNA at -80ºC.

Control group
Patients who have sicca syndrome but do not meet the classification criteria of Sjögren's syndrome, therefore, at the time of evaluating these patients to determine whether or not they have the disease are what will serve as controls since according to the usual diagnostic process, the same studies will be carried out as for patients with the proposed disease. Will receive salivary gland biopsy.
Procedure: Biopsy Salivary Gland
A minor salivary gland biopsy will be performed at lower lip, with the minimally invasive technique that is carried out in Rheumatology Unit as a routine procedure for the diagnosis of pSS, from there it will be taken between 2-3 glands for the study. RNAlater®(Ambion, Inc., Texas, United States of America) will be stored in solution for the stabilization and preservation of RNA at -80ºC.




Primary Outcome Measures :
  1. Gene expression levels in immune cells in salivary gland biopsy samples from participants with and without pSS [ Time Frame: Up to 24 months ]
    To identify a biomarker of disease activity, measured by the real-time PCR reactions (qRT-PCR).

  2. Gene expression levels in immune cells in blood samples from participants with and without pSS [ Time Frame: Up to 24 months ]
    To identify a biomarker of disease activity, measured by the real-time PCR reactions (qRT-PCR).

  3. Gene expression levels in immune cells in saliva samples from participants with and without pSS [ Time Frame: Up to 24 months ]
    To identify a biomarker of disease activity, measured by the real-time PCR reactions (qRT-PCR).


Secondary Outcome Measures :
  1. Immunoglobulins [ Time Frame: Up to 24 months ]
    The change from baseline in IgG, IgM and IgA levels at 24 months.

  2. Complement levels C3 and C4 [ Time Frame: Up to 24 months ]
    The change from baseline in complement levels at 24 months.

  3. Rheumatoid Factor [ Time Frame: Up to 24 months ]
    The change from baseline in titer of rheumatoid factors at 24 months.

  4. Cryoglobulins [ Time Frame: Up to 24 months ]
    The change from baseline in titer of cryoglobulins at 24 months.


Biospecimen Retention:   Samples With DNA
Salivary gland, saliva, blood samples


Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Participants with sicca and primary Sjogren Syndrome will be recruited from multiple sites.
Criteria

Inclusion Criteria:

  • Patients: cross sectionally patients will be included for clinical suspicion of primary SS or with the diagnosis already established in Rheumatology unit.

The following inclusion criteria will be applied to the study:

  • Age > 18 years
  • Informed consent of the patient.

Exclusion Criteria:

  • Impossibility of obtaining consent (cognitive impairment, other causes).
  • Associated systemic autoimmune or rheumatological diseases.
  • Chronic viral infections (HCV, HBV, HIV).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03765593


Contacts
Contact: Maria Soledad Retamozo, MD, PhD 005493516981622 soleretamozo@hotmail.com
Contact: Eduardo Cuestas, MD, PhD 005493516609303 eduardo.cuestas@gmail.com

Sponsors and Collaborators
National Council of Scientific and Technical Research, Argentina
Investigators
Principal Investigator: Maria Soledad Retamozo, MD, PhD INICSA-Universidad Nacional de Córdoba-CONICET, Córdoba, Argentina

Publications of Results:

Other Publications:
Responsible Party: Maria Soledad Retamozo, Research Assistant, National Council of Scientific and Technical Research, Argentina
ClinicalTrials.gov Identifier: NCT03765593     History of Changes
Other Study ID Numbers: 3398
First Posted: December 5, 2018    Key Record Dates
Last Update Posted: December 5, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Maria Soledad Retamozo, National Council of Scientific and Technical Research, Argentina:
Primary Sjogren Syndrome
Lymphoma
Biomarker

Additional relevant MeSH terms:
Eye Diseases
Syndrome
Sjogren's Syndrome
Lymphoma, Non-Hodgkin
Disease
Pathologic Processes
Arthritis, Rheumatoid
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Xerostomia
Salivary Gland Diseases
Mouth Diseases
Stomatognathic Diseases
Dry Eye Syndromes
Lacrimal Apparatus Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders