Protocol Number: 08-D-0018

Title:

Clinical and Laboratory Evaluation of the Autonomic Nervous System in Primary Sjogren's Syndrome

Number:

08-D-0018

Summary:

Background:

Sjogren's Syndrome (SS) is an autoimmune disease that affects the glands that produce saliva and tears, causing dry eyes and dry mouth.

Researchers do not know the exact cause of SS, but they believe that it may be caused by abnormalities in the autonomic nervous system (ANS) that stimulate these glands.

Objectives:

To better understand ANS function in patients with SS.

To compare information about ANS function in healthy individuals and in patients with SS.

Eligibility:

Patients with Sjogren's Syndrome who are 18 years of age and older, and who are not pregnant or breastfeeding.

Participants will be asked to taper or discontinue the use of certain medications or dietary supplements before the ANS testing.

Participants must be willing to discontinue the use of alcohol and tobacco 24 hours prior to testing.

Design:

The study will require one inpatient admission and/or outpatient visits to the NIH Clinical Center.

The following tests and procedures will be performed:

-Saliva, tear, and sweat production measurements to evaluate the function of glands.

-Testing of changes to the cardiovascular system, including blood pressure and blood flow testing, and an electrocardiogram - designed to evaluate hemodynamic changes controlled by the ANS.

-Testing of changes to the gastrointestinal system, including a swallowing assessment study, barium swallow study, and gastric emptying study - designed to evaluate gastrointestinal function controlled by the ANS.

-Tests to evaluate the ANS function in response to certain drugs (edrophonium, glucagon and acetylcholine).

-Self-reported questionnaire on ANS function and emotional/psychological well-being.

Additional procedures and tests may include the following:

-Blood samples.

-Optional skin biopsy to study sweat glands and nerve supply of the skin.

Sponsoring Institute:

National Institute of Dental And Craniofacial Research (NIDCR)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

1. Diagnosis of primary Sjogren's syndrome based on American-European Consensus Group Sjogren's syndrome classification criteria or normal volunteers.

2. Both genders and all minorities.

3. Age at entry at least 18 and less than 65 years.

EXCLUSION CRITERIA:

1. Exclusion criteria for primary Sjogren's syndrome:

-Past head and neck radiation therapy

-Hepatitis C infection

-AIDS

-Pre-existing lymphoma

-Sarcoidosis

-GVHD

-Current use of medications (see note below) known to significantly influence the activity of the sympathetic or parasympathetic nervous system if they cannot be held safely at the time of ANS testing

2. Diagnosis of a concomitant autoimmune disorder that would qualify for secondary Sjogren's syndrome

3. No known co-existing diagnosis of ANS dysfunction (for normal volunteers)

4. Medications-requiring diabetes mellitus

5. Diabetic autonomic neuropathy

6. Vitamin B12, folate deficiency, requiring replacement

7. Hepatic failure (AST or ALT greater than 1.5 x upper limit of normal)

8. Renal failure (GFR less than 30 ml/min, as estimated by the MDRD)

9. Congestive heart failure (Class II-IV)

10. Refractory ventricular arrhythmias

11. Symptomatic coronary heart disease

12. Previously established diagnosis of sinus node dysfunction

13. Severe anemia (Hgb less than 8)

14. Psychosis

15. Pregnant or lactating women

16. Women of childbearing potential must have a negative urine or blood test for pregnancy done within 24 hours before any testing involving radioactivity or investigational drug administration.

17. A candidate subject is excluded if, in the judgment of the Principal Investigator, protocol participation would place the subject at substantially increased acute medical risk.

18. Not able to provide informed consent

Medications: A candidate subject is excluded if clinical considerations require that the patient continue treatment with a drug likely to interfere with the scientific results i.e. a tricyclic antidepressant or fludrocortisone. Patients with known or suspected allergy or hypersensitivity to any test drug are excluded from receiving that drug. Patients who must take medications daily in the following categories are excluded: tricyclic antidepressants, beta blockers, barbiturates, if they cannot be safely held during testing. Patients unable to discontinue nicotine or alcohol temporarily are excluded. Patients are not to discontinue any medications before the patient or the patient's physician discusses this with the Principal Investigator, Dr. Nikolov, or the Associate Investigator, Dr. Goldstein. If it is decided that discontinuing medications would be unsafe, then the patient is excluded from the study. Subjects must discontinue use of alcohol and tobacco throughout the period of testing in the protocol.

Herbal Medicines and Dietary Supplements: Certain herbal medicines or dietary supplements are known or suspected to interfere with the experimental results, and such herbal medicines or dietary supplements must be discontinued before enrollment in the study. For many herbal medicines or dietary supplements, the mechanisms of action and therefore the possible effects on the experimental results are unknown. In cases where the subjects wish to continue their herbal medicines or dietary supplements while on study, and search of the available medical literature fails to identify effects that are known or expected to interfere with the experimental results, then the subjects may participate.

Special Instructions:

Currently Not Provided

Keywords:

Autonomic Nervous System

Sjogren's Syndrome

Pathogenesis

Cholinergic

Parasympathetic

Recruitment Keyword(s):

Sjogren Syndrome

Condition(s):

Sjogren's Syndrome

Dysautonomia

Investigational Drug(s):

Acetylcholine

Investigational Device(s):

None

Intervention(s):

None

Supporting Site:

National Institute of Dental and Craniofacial Research

Contact(s):

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):

Andonopoulos AP, Christodoulou J, Ballas C, Bounas A, Alexopoulos D. "Autonomic cardiovascular neuropathy in Sjogren's syndrome. A controlled study." J Rheumatol. 1998 Dec;25(12): 2385-8.

Arbuckle MR, McClain MT, Rubertone MV, Scofield RH, Dennis GJ, James JA, HarleyJB. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med. 2003 Oct 16;349(16):1526-33.

Bjšrklund H, Dalsgaard CJ, Jonsson CE, Hermansson A. Sensory and autonomic innervation of non-hairy and hairy human skin. An immunohistochemical study. Cell Tissue Res. 1986;243(1):51-7.

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