Characterization of Diseases With Salivary Gland Involvement

Background:

- Salivary glands in and around the mouth and throat make saliva. Salivary gland disorders can affect a person s quality of life. Studying people who have a disease that affects their salivary gland(s) may teach researchers about the disorders and their genetics.

Objectives:

- To study salivary gland diseases and disorders. To collect data and samples from people with salivary gland problems and their relatives.

Eligibility:

• People more than 4 years old who have or are suspected to have a disease involving salivary glands.
• Their relatives more than 4 years old.
• Healthy volunteers 18 years or older.

Design:

• Participants may be screened with:
• Medical history
• Physical exam
• Blood and urine tests
• General oral and dental history and exam
• Saliva collection
• Eye exam and test for dry eyes
• Health questionnaires (adults)
• Biopsy of some minor salivary glands. A small incision will be made on the inside of the lower lip and several tiny salivary glands will be removed.
• Participants will have 2 3 visits. These may include:
• Repeats of some screening tests
• Ultrasounds of some glands. Researchers will put some gel on the face, then press on it with a smooth wand.
• Adults may have other biopsies
• A small catheter inserted into the opening of the parotid gland duct on the inside of the cheek. A saline solution (in a syringe) will fill the duct.
• Swishing a saltwater solution in the mouth for 10 seconds and then spitting into a cup
• Scrapings collected from teeth, tongue, and cheeks

Study Overview

• Status: Recruiting
• Conditions: Healthy Volunteer; Sjogren's Syndrome; Salivary Gland Disease

Detailed Description

This protocol is intended to allow disease-specific investigations in subjects with presentations of diseases with salivary gland involvement and will enable the collection of data, biological fluids and tissue samples from those subjects, their family members and normal controls, in order to assist our studies of understanding salivary gland disease pathophysiology. The exocrine salivary glands, by secreting saliva, play a critical role in the homeostasis of the oral cavity, which is the initial part of the gastrointestinal track. Several diseases including Parkinson s and systemic amyloidosis can be diagnosed through biopsies of easily accessible salivary glands. Moreover, several drugs and systemic diseases cause salivary gland hypofunction through unknown mechanisms.

We may evaluate participants with complaints of dry mouth to determine the cause and severity of their salivary gland dysfunction and their possible eligibility for other NIDCR protocols. Salivary secretions have antibacterial, lubricating, remineralizing, digestive, buffering and cleansing properties. Impaired function of these glands can cause an increase in tooth decay; a variety of oral hard and soft tissue changes, with painful, burning or ulcerated or oral mucosa; problems chewing, swallowing and speaking; and diminished taste and smell.

This protocol will provide us with the opportunity to learn from a variety of pathologies that involve directly or indirectly the salivary glands, expand our knowledge about these disorders and provide access to patients of interest for research, teaching, and clinical experience. Information obtained through this protocol may lead to potential innovative therapeutic studies. In addition to its role in investigating individuals who are of interest to the Sjogren s syndrome (SS) and Salivary Gland Dysfunction Unit of the MPTB of NIDCR, this protocol can provide a possible avenue for enrolling subjects from other NIH programs or other NIH protocols that exhibit signs or symptoms associated with the salivary glands dysfunction.

• Study Type: Observational
• Enrollment (Estimated): 1150

Contacts and Locations

• Study Contact: Name: Eileen M Pelayo; Phone Number: (301) 594-3097; Email: eileen.pelayo@nih.gov
• Study Contact Backup: Name: Margaret E Beach, P.A.-C; Phone Number: (301) 451-3479; Email: margaret.beach@nih.gov

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • National Institutes of Health Clinical Center
      • Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR); Phone Number: TTY dial 711 800-411-1222; Email: ccopr@nih.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Subjects with known or suspected Sjogren's syndrome and their family members (affected and unaffected) are potentially eligible participants. Subjects with other causes of salivary gland dysfunction (including hepatitis C) may also be potentially eligible for participation.

Description

• INCLUSION CRITERIA:
• Persons older than 4 years of age, affected with or suspected of being affected with a disease/disorder involving the salivary glands or who is a relative of a person who is affected with these diseases/disorders.

Or,

- Persons 18 years or older with active hepatitis with or without sicca symptoms and patients undergoing immunotherapy with an immune checkpoint inhibitor for oral cancer.

Specific to patients undergoing immunotherapy with an immune checkpoint inhibitor for threatment of oral cancer, these patients will be seen before and after check point inhibitor therapy which will coincide with 4 weeks (+/-2 weeks) before and again immediately before (+/- 2 weeks) definitive oral cancer treatment initiation (e.g., surgical resection, etc.).

Or,

- Healthy persons age 18 or older, who agree to have blood, urine, saliva or tissue samples collected and studied.

EXCLUSION CRITERIA:

• Anyone not able to give consent/assent or parental/guardian consent
• NIH employees who report directly to the principal investigator

• Significant concurrent medical condition or other circumstances that may affect the participant s ability to tolerate or complete the study, such as concurrent chemotherapy or bleeding disorders.

  • Specific only to the immune checkpoint inhibitor patients, oral cancer as a serious concurrent medical condition, will not serve as an exclusion criteria.
  • Moreover, these immune checkpoint inhibitor subjects, if unable to tolerate the study procedures, such as salivary gland biopsies, saliva collections, and/or oral exams, will be excluded as determined by the Principal Investigator.

• Additional exclusion criteria for Healthy Volunteers (HV):

  • Pregnancy
  • Sicca Symptoms
  • HIV, hepatitis B or C infection
  • Chronic medical illness, other than well-controlled hypertension or hyperlipidemia
  • Chronic use of medications, with the exception of oral contraception, hormone replacement therapy, aspirin, antihypertensives and antilipemics

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Group 1; Healthy Volunteers matched with Sjogren's Syndrome patients
Group 2; Family Members, affected and unaffected
Group 3; any other cause salivary gland dysfunction

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
hypothesis generating	hypothesis generating	hypothesis generating

Collaborators and Investigators

• Sponsor: National Institute of Dental and Craniofacial Research (NIDCR)
• Investigators: Principal Investigator: Margaret E Beach, P.A.-C, National Institute of Dental and Craniofacial Research (NIDCR)

Publications and helpful links

General Publications

• Yin H, Pranzatelli TJF, French BN, Zhang N, Warner BM, Chiorini JA; NIDCD/NIDCR Genomics and Computational Biology Core. Sclerosing Sialadenitis Is Associated With Salivary Gland Hypofunction and a Unique Gene Expression Profile in Sjogren's Syndrome. Front Immunol. 2021 Jul 30;12:699722. doi: 10.3389/fimmu.2021.699722. eCollection 2021.
• Tanaka T, Warner BM, Odani T, Ji Y, Mo YQ, Nakamura H, Jang SI, Yin H, Michael DG, Hirata N, Suizu F, Ishigaki S, Oliveira FR, Motta ACF, Ribeiro-Silva A, Rocha EM, Atsumi T, Noguchi M, Chiorini JA. LAMP3 induces apoptosis and autoantigen release in Sjogren's syndrome patients. Sci Rep. 2020 Sep 16;10(1):15169. doi: 10.1038/s41598-020-71669-5.

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2015
• Primary Completion (Estimated): April 1, 2032
• Study Completion (Estimated): April 1, 2032

Study Registration Dates

• First Submitted: December 30, 2014
• First Submitted That Met QC Criteria: December 30, 2014
• First Posted (Estimated): December 31, 2014

Study Record Updates

• Last Update Posted (Actual): March 29, 2024
• Last Update Submitted That Met QC Criteria: March 28, 2024
• Last Verified: February 27, 2024

More Information

Terms related to this study

• Keywords: Genetics; Sjogren's Syndrome; Dry Mouth; Gland dysfunction; Induced Pluripotent Stem (iPS) Cell Lines
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Eye Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Stomatognathic Diseases; Mouth Diseases; Lacrimal Apparatus Diseases; Arthritis, Rheumatoid; Xerostomia; Dry Eye Syndromes; Sjogren's Syndrome; Salivary Gland Diseases
• Other Study ID Numbers: 150051; 15-D-0051

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: .This is an observational study that began enrolling in 2015. De-identified data will be made public consistent with the policies of the NIH.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No