Dexamethasone Irrigation of the Parotid Glands in Primary Sjögren's Syndrome Subjects
Condition: Sjögren's Syndrome; Xerostomia
MeSH terms: Sjogren's Syndrome; Xerostomia; Syndrome
Intervention: Dexamethasone Parotid Irrigation; Placebo Parotid Irrigation
Intervention description: Irrigation of the parotid gland from one side of the mouth with dexamethasone.; Irrigation of the parotid gland on the opposite side of the mouth with placebo saline.
Intervention MeSH terms: Dexamethasone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Double (Participant, Investigator)
Enrollment: 14.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Xerostomia; Sjögren's Syndrome; Interventional Study; Sjogren's Syndrome; Dry Mouth

Summary:

      Background:

      Sjögren's syndrome is an autoimmune disease (where the immune system attacks normal body
      tissues) that affects the salivary glands. Many people with Sjögren's syndrome are not able
      to make enough saliva because their salivary glands are inflamed. The dry mouth that results
      can interfere with daily activities and can lead to dental cavities, mouth sores, and
      infections. Injections of corticosteroids into the parotid glands can improve saliva
      production in people with Sjögren's syndrome, but current treatment practices may provide
      only temporary relief. Researchers are interested in studying the effectiveness of stronger
      corticosteroid injections (using dexamethasone) to determine how the corticosteroid treatment
      actually works.

      Objectives:

      - To evaluate the effectiveness and mechanics of dexamethasone injections to improve saliva
      production in individuals with primary Sjögren's syndrome.

      Eligibility:

      - Women between 18 and greater of age who have been diagnosed with primary Sjögren's
      syndrome, and have had a biopsy of the minor salivary glands in the past 5 years that shows a
      moderate level of inflammation.

      Design:

        -  Participants will be screened with a full medical history and physical examination,
           blood and urine tests, and salivary gland biopsies. Participants will also be screened
           with tests of saliva flow production and evaluation of the salivary ducts and glands,
           and will complete questionnaires about dry mouth symptoms.

        -  At the first treatment visit, participants will receive an injection of dexamethasone
           into one parotid gland and an injection of saline into the other gland. After the
           injections, participants will provide a blood sample to test the level of dexamethasone
           in the blood.

        -  Two weeks after the first treatment, participants will return for an evaluation visit to
           have saliva flow rate measurements taken, and will complete a questionnaire about dry
           mouth symptoms.

        -  Four weeks after the first treatment, participants will have a second treatment for each
           parotid gland, with the same tests and questionnaires as before.

        -  Participants will have additional evaluation visits 6 and 8 weeks after the first
           treatment visit, with a followup telephone call approximately 6 weeks after the last
           dexamethasone treatment visit.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

          -  Female gender and age 18 and greater.

          -  Diagnosed with primary SS in Protocol 84-D-0056.

          -  Stimulated salivary flow of at least 0.01 mL/min from each parotid gland, using the
             standard operating procedure (SOP) for the National Institute of Dental and
             Craniofacial Research (NIDCR) Molecular Physiology and Therapeutics Branch (MPTB)
             Sjögren's Syndrome Clinic

          -  Minor salivary gland (MSG) biopsy with a focus score of greater than or equal to 1
             obtained 0 to 7 years prior to study enrollment. Biopsies from outside of the National
             Institutes of Health (NIH) must be reviewed by the NIH Pathology Department. An MSG
             biopsy will be required for the following situations:

          -  The last biopsy was obtained before the use of rituximab.

          -  The last biopsy was obtained before the use of immunosuppressants, biologics, or
             disease-modifying antirheumatic drugs for more than 3 months.

          -  The last biopsy was obtained before the use of systemic corticosteroids (for more than
             2 weeks or for shorter periods at doses of more than 0.5 mg/kg) or local parotid
             corticosteroids. The use of topical or intra-articular/periarticular corticosteroids
             will not require a repeat biopsy.

          -  For women of childbearing potential, use of, or willingness to use, an effective
             method of birth control during the study. Effective methods include abstinence,
             history of hysterectomy, tubal ligation, intrauterine device, licensed hormonal
             methods, condoms, diaphragm, and cervical cap.

          -  Ability to provide written informed consent prior to entry in the study.

        EXCLUSION CRITERIA:

          -  History of lymphoma.

          -  History of mycosis, aspergillosis, or other deep fungal infection of the parotid
             gland.

          -  History of salivary gland malignancy (primary or metastatic to the salivary gland).

          -  History of secondary Sjögren's syndrome.

          -  Parotid infection that does not resolve at least 4 weeks before the start of the
             Screening Period.

          -  Any active viral infection that does not resolve by the start of the Screening Period.

          -  Pregnancy or lactation.

          -  Use of biologics within 3 months of the start of the Screening Period.

          -  Any experimental therapy within 3 months before the start of the Screening Period.

          -  Use of immunosuppressants such as methotrexate, leflunomide, azathioprine,
             cyclophosphamide, systemic cyclosporine, or systemic corticosteroids within 3 months
             prior to the start of the Screening Period.

          -  Use of inhaled corticosteroids within 3 months prior to the start of the Screening
             Period.

          -  Use of antimalarials and regular use of NSAIDs unless the dose has been stable (or
             decreased) for at least 2 months.

          -  Inability to discontinue the use of saliva stimulants such as pilocarpine and
             cevimeline for 24 hours before each study visit.

          -  Parotid intraductal irrigation or instillation with steroids within the past year.

          -  Use of rituximab within 6 months prior to the start of the Screening Period.

          -  Allergy to steroids or technetium, or any components of the formulations.

          -  Current use of warfarin or heparin.

          -  History of bleeding disorder.

          -  Both severe atrophy and fibrosis of the MSG noted on the pathology report of the MSG
             biopsy.

          -  Inability to comply with protocol procedures and the number of required visits.

          -  Inability to cannulate one or both parotid glands.

          -  Parotid fill volume less than 0.5 mL in one or both parotid glands.

          -  Significant concurrent medical condition or other circumstances that, in the opinion
             of the principal investigator, could affect the subject's ability to tolerate or
             complete the study.

          -  Unable to understand written English for completion of study questionnaires.