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Treatment of Primary Hyperparathyroidism With Denosumab and Cinacalcet. (NCT03027557)

Aalborg University
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.
  • Drug: Cinacalcet 30 mg Tablet
    Participants in one arm will receive 30 mg cinacalcet each day.
    • Mimpara
    • Sensipar
  • Drug: Denosumab Inj 60 mg/ml
    Participants in two arms will receive 60 mg Denosumab biannually.
    • Prolia
    • Xgeva
  • Other: Placebo tablets
    Participants in two arms will receive one placebo-tablet each day.
    • Other: Saline Injection (Placebo)
      Participants in one arm will receive saline injections as placebo for denosumab.
      • NaCl Fresenius "Kabi"
    Ages eligible for Study
    18 Years and older
    Genders eligible for Study
    All
    Accepts Healthy Volunteers
    No
    Inclusion Criteria:
    • Men and women of 18 years of age or older.
    • T-score by 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 QTc-interval.Risk factors of prolonged QTc-interval.
    • 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 IMP's.
    • 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.
    Background/Context:

    This project deals with medical treatment of primary hyperparathyroidism. The only cure currently available is surgical removal of one or more parathyroid glands, but this option is neither feasible, nor desirable in all patients with the diagnosis.

    Today a major group of patients are being diagnosed by coincidence with biochemical blood-screening, and are therefore in an asymptomatic state of the disease at the time of diagnosis. Long term studies show that these patients over time often have progression in their disease, and develop complications such as osteoporosis. Thus a medical alternative is warranted.

    Previous studies have investigated the effects of well known antiresorptive drugs such as bisphosphonates, as well as estrogen-related compounds. These drugs have had effects on particularly bone mineral density (BMD) and biochemical bone-turnover markers, but have been able only transiently to lower blood-calcium levels. Combined with too many unwanted side-effects and a high prevalence of contraindications for a large proportion of the patients needing treatment, these drugs have not provided a realistic alternative to surgery.

    Treatment today generally follows the international consensus for treatment of asymptomatic patients with primary hyperparathyroidism. Briefly this includes watchful waiting with biannual control-sessions for indication of surgery, screening for kidney stones/nephrolithiasis, osteoporosis and s-calcium - and s-iPTH levels.

    This randomized controlled trial involves the drugs Cinacalcet og Denosumab. Denosumab has previously been shown to greatly improve BMD, lower s-calcium, lower the rate of bone-turnover and prevent osteoporotic fractures in several populations with different diseases, but has never been tested in a published randomized controlled trial in patients with primary hyperparathyroidism.

    Cinacalcet has been proved able to lower s-iPTH, lower s-Calcium and thereby relieve symptoms of hypercalcaemia caused by primary hyperparathyroidism. It does not however, lower the rate of bone turnover, and it has not been show to improve BMD.

    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-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.

    1 locations

    Denmark (1)
    • Aalborg University Hospital
      Aalborg, Denmark, 9000
    Status:
    enrolling by invitation
    Type:
    Interventional
    Phase:
    Start:
    28 February, 2017
    Updated:
    26 June, 2017
    Participants:
    60
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