Treatment of Primary Hyperparathyroidism With Denosumab and Cinacalcet.
Condition: Primary Hyperparathyroidism; Parathyroid Adenoma; Parathyroid Hyperplasia
MeSH terms: Adenoma; Parathyroid Neoplasms; Hyperparathyroidism; Hyperparathyroidism, Primary; Hyperplasia
Intervention: Cinacalcet 30 mg Tablet; Denosumab Inj 60 mg/ml; Placebo tablets; Saline Injection (Placebo)
Intervention description: Participants in one arm will receive 30 mg cinacalcet each day.; Participants in two arms will receive 60 mg Denosumab biannually.; Participants in two arms will receive one placebo-tablet each day.; Participants in one arm will receive saline injections as placebo for denosumab.
Intervention MeSH terms: Denosumab; Cinacalcet
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 46.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Primary Hyperparathyroidism; Parathyroid Adenoma; Parathyroid Hyperplasia; Cinacalcet; Denosumab; Drug Therapy; Bone Mineral Density; Calcium

Summary:

      The only known cure for primary hyperparathyroidism is surgical removal of one or more
      parathyroid glands. Some patients however, do not fulfill criteria for surgery or do not want
      to undergo a procedure due to fear of the associated risks. Therefore a medical alternative
      is warranted.

      This study aims to evaluate the effects of Denosumab alone, and in combination with
      Cinacalcet, as a medical treatment for patients suffering from primary hyperparathyroidism,
      with mild osteoporosis. To the best of our knowledge no previously reported randomized
      controlled trial has investigated the use of denosumab in primary hyperparathyroidism.

      60 patients will be enrolled in three different treatment-groups: 20 receiving both Denosumab
      and Cinacalcet, 20 Denosumab and placebo and 20 placebo and placebo. Patients included do not
      meet the criteria for, or have no wish for a surgical procedure.

      By combining the two drugs, this study could possibly contribute to the discovery of a
      realistic medical alternative to surgery. It is expected that the therapy will be able to
      both control s-calcium and s-intact parathyroid hormone (iPTH), and simultaneously enhance
      bone-structure. The therapy thus has the potential of preventing fractures and possibly other
      long-term effects of primary hyperparathyroidism such as formation of kidney stones, and
      coronary calcification. Another objective of this project is to investigate whether the
      combined therapy can facilitate an actual reset of the Calcium-sensing receptor, and thereby
      de facto cure the disease.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Men and women of 18 years of age or older.

          -  T-score by Dual X-ray Absorptiometry (DXA) between -1,0 og -3,5

          -  Patients from The North Jutland Region diagnosed with primary hyperparathyroidism at
             the Department of Endocrinology, Aalborg University Hospital. (Hypercalcaemia measured
             at two different time-points and simultaneous elevated/inappropriately high PTH, and
             exclusion of differential diagnosis.)

        Exclusion Criteria:

          -  Medical history of diseases leading to hypercalcaemia other than Primary
             Hyperparathyroidism.

          -  Patients being treated with Denosumab or Cinacalcet prior to inclusion or previously
             treated with Denosumab or Cinacalcet.

          -  Moderately - Severely decreased liver function (alanine aminotransferase >250u/l,
             gamma-glutamyl transferase>150u/l, Bilirubin >30)

          -  Acute myocardial infarction or apoplexia in the 3 months before inclusion.

          -  Medical record of heart failure

          -  Risk factors of prolonged corrected QT interval (QTc).

          -  Open lesions from oral surgery.

          -  Primary diseases of the bone other than osteoporosis.

          -  Patients suffering from kidney disease or renal failure.

          -  Patients under treatment with thiazide or lithium.

          -  Medical record of generalized seizures or epilepsy.

          -  Active malignant disease.

          -  Known allergies towards the specified medicinal products (IMPs).

          -  Pregnancy or breastfeeding.

          -  Fertile women who do not agree to the usage of effective contraception.

          -  Other circumstances, evaluated by the responsible investigator, making the subject
             unsuitable for participation.