The Effect of Cinacalcet on Gastric Acid Output in Healthy Subjects

The purpose of this study is to determine whether cinacalcet will increase gastric acid secretion in healthy volunteers.

The calcium sensing receptor (CaSR) was originally found on parathyroid and renal cells and more recently it has been identified on cells that regulate gastric acid secretion (G cells and parietal cells). However, its role in regulating acid secretion in humans is completely unknown and is of potential importance because an acid environment in the stomach enhances intestinal calcium absorption. In this pilot project, we will stimulate the CaSR with a CaSR-agonist called cinacalcet. Our hypothesis is that activation of the CaSR will in turn increase gastric acid production in healthy volunteers.

Inclusion Criteria:

• Healthy ambulatory men and postmenopausal women
• Age 45 to 70
• Avoid alcohol, antacids, H2 blockers, proton pump inhibitors, or antihistamines during the study.

Exclusion Criteria:

• Ionized Ca++ level <4.39 mg/dl or >5.02 mg/dl (normal reference range 4.18- 5.02).
• 24-hour UCa++ excretion >350 mg.
• Cr >1.3.
• AST/ALT values >10% beyond reference range.
• Hgb level <11.7 g/dl in women and <13.2 g/dl in men.
• MCV level >102 UM3.
• Basal acid output >5 mEq/h in men and >3.8 mEq/h in women.
• Basal acid output <1 mEq/h in men and <0.2 mEq/h in women.
• Age <45 or >70.
• Premenopausal or <1 year post-menopause.
• Individuals following vegan diets.
• Current EtOH abuse.
• Lidocaine allergy. Medications
• Antacids
• H2 blockers
• Proton pump inhibitors
• Carafate
• Anticholinergic agents (i.e. TCA)
• Cholinergic agents
• Antihistamines in the last 3 weeks
• Cogentin
• Adrenergic blockers
• Thiazide diuretics
• Antiplatelet drugs
• Oral and Inhaled Glucocorticoids
• Bisphosphonates
• Raloxifene, Tamoxifen
• Tobacco
• EtOH during study
• rPTH
• Calcitonin
• Ketoconazole/Itraconazole
• Calcitriol
• Paricalcitol
• Drisdol, Ergocalciferol
• Phosphate binders
• Anticoagulant
• Erythromycin
• Hormone replacement therapy except vaginal estrogen creams

Exclusion Diseases

• Achlorhydria
• Pernicious anemia
• Zollinger Ellison syndrome
• Congestive heart failure
• Esophageal strictures or motility problems
• History of a GI bleed
• Prior upper GI surgery
• Malabsorption
• History of GI malignancy
• GERD, gastritis, duodenitis
• Active peptic ulcer disease
• Gallbladder disease
• Liver disease
• Pancreatitis
• Current kidney stone
• Renal disease
• Current hypoparathyroidism or hyperparathyroidism
• Moderate to Severe coronary artery disease
• Aortic aneurysm
• Seizure disorder
• Current Arrhythmia