The Functioning of Immune and Hormonal Systems in Patients With Sjogren's Syndrome and in Healthy Volunteers
The Functioning of Immune and Hormonal Systems in Patients With Sjogren's Syndrome and in Healthy Volunteers
This study aims to learn more about how the immune and hormonal systems function in patients
 with Sjogren's syndrome, a disease in which the immune system does not function properly.
 Adult nonpregnant females are invited to participate. Oral contraceptives may not be taken
 for 6 weeks before and during this study, so another form of birth control must be used, such
 as abstinence.

 There will be two visits. At the first visit, a medical history and physical examination will
 be conducted, and blood and urine tests will be done. The total amount of blood drawn will be
 10 tablespoons. This visit will last 3 hours. At the second visit, participants will have an
 oral glucose tolerance test. To prepare for it, they must be on a special diet for 3 days
 beforehand and keep a diary of eating, sleeping, and physical activities for those 3 days. A
 urine sample will be taken at the beginning of the visit. Subjects must then drink a very
 sweet carbonated cola. A small plastic tube will be placed into an arm vein. Blood will be
 drawn through this tube eight times over 3 hours. The total amount of blood drawn will be 17
 tablespoons.

 Only minor inconveniences are anticipated as a result of participating in this study. Risks
 from blood tests include soreness, bruising, and minor infection at the puncture site, and
 dizziness. The oral glucose tolerance test may cause temporary stomach bloating, headache,
 nausea, and vomiting.
Sjogren's syndrome is a chronic systemic disease that primarily affects the salivary and
 lacrimal glands and is characterized by lymphocytic tissue infiltration and auto-antibody
 production. The pathogenesis of Sjogren's syndrome is unknown. We hypothesize that reduced
 somatostatin activity is an important factor in promoting immune dysregulation in patients
 affected by Sjogren's syndrome. Somatostatin is a multifunctional peptide with potent
 immunomodulatory properties whose effects are reduced lymphocytic activity, reduced
 gastrointestinal secretions, activation of the hypothalamic-pituitary axis,
 anti-inflammatory, etc. As several findings in Sjogren's syndrome are opposite to those
 produced by somatostatin, it is logical to consider that the activity of this peptide is low
 in patients affected by this disease. The purpose of this study is to determine whether basal
 and stimulated plasma levels of somatostatin and its effects on the immune and endocrine
 systems differ between 16 patients affected by primary Sjogren's syndrome and 16 healthy
 control subjects.
Female gender only, ages 18 to 75.

 Patients should have documented primary Sjogren's syndrome as determined by protocol
 84-D-0056. The diagnosis of primary Sjogren's syndrome will be based on the presence of all
 three of the following:

 Salivary gland abnormalities;

 Lacrimal gland abnormalities;

 Serologic abnormalities.

 Controls should have no signs or symptoms of Sjogren's syndrome, and negative serologic
 testing reconfirmed within 2 weeks of the OGTT.

 Willingness to: a) participate in phase I and II of the protocol; b) follow the guidelines
 set to prepare for the OGTT; and c) modify current medical therapy if necessary.

 Must be able to comply with protocol procedures.

 No patients with "incomplete" Sjogren's syndrome, i.e., with less than three positive
 findings as described above.

 No presence of physical or mental conditions that may interfere with the protocol. These
 include the following diseases and conditions:

 (Present at time of phase I/II): significant disruption of sleep-wake pattern (i.e., less
 than 4 hours of continuous sleep, on the night before the OGTT only), BMI less than 18 or
 equal to/greater than 30, anemia with Hgb less than 10 gm/dl, use of tobacco or alcohol;

 (Within the past 6 weeks): acute weight change (greater than 5%), use of contraceptives
 -BCP-, Depoprovera or Norplant), irregular menstrual cycle, lactation, blood drawing in
 excess of 50 ml, use of recreational drugs, modification of estrogen replacement therapy;

 (Within the past 6 months): chronic pattern of weight change (greater than 10%), eating
 disorders, uncontrolled hypo/hyperthyroidism, breast cancer, lymphoma or other malignancy,
 pregnancy, treatment for depression, insulinoma, VIPoma, pheochromocytoma, atrophic
 gastritis, active tuberculosis or treatment for it;

 (A history of): HIV+, sarcoidosis, secondary Sjogren's syndrome, bleeding diathesis, organ
 transplant, severe neuroendocrine, renal, cardiovascular, pulmonary or gastrointestinal
 disease (e.g., renal insufficiency, unstable angina, heart failure, severe emphysema,
 Crohn's disease), diabetes mellitus, acromegaly and mental retardation.

 No contraindications to OGTT. These include:

 Hospital inpatient status, acute illness, immobilization, starvation, severe emotional
 distress within one week of the OGTT;

 Low carbohydrate diet (less than 150 g/day) for 3 days preceding the OGTT;

 Pregnancy;

 Therapy which impairs glucose tolerance: e.g., niacin, thiazide diuretics, phenytoin,
 excess thyroxine or psychotropic drugs within 1 month of phase I, oral contraceptives
 within 6 weeks of phase I, glucocorticoid treatment within the past 6 months (or one year
 if treatment lasted over 2 weeks), Beta blockers/agonists (e.g., terbutaline) within 2 days
 of phase I;

 Diabetes mellitus;

 Glucose intolerance.

 Subjects may not take medications that can affect somatostatin levels, such as
 antidepressants, benzodiazepines, neuromodulators (e.g., cholinergic, alpha/beta
 adrenergic), oral contraceptives (BCP), steroid hormones (with the exception of estrogen
 replacement therapy -ERT-, for which subjects will be matched), immunomodulators,
 anticonvulsants (e.g., carbamazepine), cimetidine -Tagamet® (Registered Trademark)-, herbal
 remedies (because of their variable substance content). Subjects may not take drugs
 affecting gastrin secretion: antacids (e.g., Maalox® (Registered Trademark), Mylanta®
 (Registered Trademark), H(2) receptor antagonists (e.g., famotidine -Pepcid® (Registered
 Trademark)-, ranitidine -Zantac® (Registered Trademark)-), cathecolamines, atropine,
 haloperidol. To become eligible, subjects should be able to safely discontinue these
 medications at least one month prior to phase I. Antacids, H(2) antagonists and
 neuromodulators (e.g., Salagen) may be discontinued 2 days prior to phase I.

 Patients cannot have take experimental drugs within 1 month of the beginning of the
 protocol.