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;
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
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;
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;
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