FGF-23 Suppressibility by Calcitonin

Introduction:

Based on our experience with calcitonin as an FGF-23 suppressive agent in a patient with an FGF-23 producing tumor we hypothesize that calcitonin may be a physiologically important regulator of FGF-23 production and secretion in healthy humans.

Aim:

In this study we wish to examine the FGF-23 suppressive effects of calcitonin in healthy men.

Study Design:

placebo-controlled, cross-over study

Method:

• All twelve subjects are examined on two occasions, once after exposure to placebo 1 ml NaCl 0.9% subcutaneously, and once following calcitonin 200 IU/ml subcutaneously
• On both occasions frequent bloodsampling will take place, out an indwelling catheter in de forearm vein.
• Sampling times: -15, 0, 60, 120, 240, 360, and 480 minutes
• Mealtimes: Calcium and Phosphate intake standardized on both occasions
• All samples are analyzed for FGF-23, using a C-terminal FGF-23 ELISA kit (Immunotopics, San Clemente, USA) that measures intact and C-terminal fragments of FGF-23, and one that measures only intact FGF-23
• Samples obtained at T-15, T0, T240 and T480 are stored for later analysis of Ca, albumin, PO4, PTH, 25-OHD and 1,25-OHD

Endpoint:

A change of 25% in de serum FGF-23 levels in response to a single subcutaneous injection of calcitonin 200 IU.

• Drug: Calcitonin
  Calcitonin 200 IU/ml, single subcutaneous injection, experimental group
• Drug: Placebo
  NaCl 0,9 % 1ml, single subcutaneous injection, placebo group

• Experimental: 1
  Intervention: Drug: Calcitonin
• Placebo Comparator: 2
  NaCl 0,9% 2 ml, single subcutaneous injection
  Intervention: Drug: Placebo

Inclusion Criteria:

• Healthy man, who are between 20-55 years old, and have a BMI 20-27 kg/m2.

Exclusion Criteria:

• Serum creatinin >100 mmol/L, or glomerular filtration rate <80 ml/min.
• Abnormal serum Ca, PO4, albumin, 25-OH vitamin D, or PTH levels.
• Any medication.