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Primary HyperparathyroidismPhase 3DENOCINANCT03027557

Treatment of Primary Hyperparathyroidism With Denosumab and Cinacalcet.

A Phase 3 study testing Cinacalcet 30 mg Tablet and Denosumab Inj 60 mg/ml in people with Primary Hyperparathyroidism and Parathyroid Adenoma, run by Peter Vestergaard at 1 site in Denmark.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cinacalcet 30 mg Tablet and Denosumab Inj 60 mg/ml
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
46 participants
Where
1 siteDenmark
Study dates
1 Mar 2017to 12 Sep 2019
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.)

Who cannot join

  • 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).
Show all 16Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

Denmark1 site
  • Aalborg University Hospital

    Aalborg, 9000

Other trials in Denmark

About this study

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.

Read more

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.

Read the detailed description

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.

Being tested
Cinacalcet 30 mg Tablet, Denosumab Inj 60 mg/ml, Placebo tablets, Saline Injection (Placebo)
Keywords
Primary Hyperparathyroidism, Parathyroid Adenoma, Parathyroid Hyperplasia, Cinacalcet, Denosumab, Drug Therapy, Bone Mineral Density, Calcium
Medical subject headings
Hyperparathyroidism, Primary, Parathyroid Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cinacalcet 30 mg TabletDrug

    Also called Mimpara, Sensipar

    Participants in one arm will receive 30 mg cinacalcet each day.

  • Denosumab Inj 60 mg/mlDrug

    Also called Prolia, Xgeva

    Participants in two arms will receive 60 mg Denosumab biannually.

  • Placebo tabletsOther

    Participants in two arms will receive one placebo-tablet each day.

  • Saline Injection (Placebo)Other

    Also called Sodium Chloride (NaCl) Fresenius "Kabi"

    Participants in one arm will receive saline injections as placebo for denosumab.

Study groups in NCT03027557
Study groupRoleWhat they receive
Combined treatment.Experimental20 subjects will be treated with combined 60mg denosumab bi-annually , 30 mg cinacalcet daily and 50 micrograms vitamin-D daily.
Receives: Drug: Cinacalcet 30 mg Tablet; Drug: Denosumab Inj 60 mg/ml
MonotherapyActive comparator20 subjects will receive 60mg denosumab bi-annually, placebo and 50 micrograms vitamin-D daily.
Receives: Drug: Denosumab Inj 60 mg/ml; Other: Placebo tablets
PlaceboPlacebo comparator20 subjects will receive a saline injection bi-annually (blinded), placebo-tablets and 50 micrograms vitamin-D daily.
Receives: Other: Placebo tablets; Other: Saline Injection (Placebo)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Lumbar Spine Bone Mineral Density

    Change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan.

    Measured: Baseline,one year

  2. Change in Total Hip Bone Mineral Density

    Change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan.

    Measured: Baseline,one year

  3. Change in Femoral Neck Bone Mineral Density

    Change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan.

    Measured: Baseline,one year

  4. Change in 1/3 Forearm Bone Mineral Density

    Change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan.

    Measured: Baseline,one year

  5. Percentage Change in Lumbar Spine Bone Mineral Density

    Percentage change of Bone Mineral Density after one year of treatment from baseline.

    Measured with Dual-energy X-ray absorptiometry (DXA)-scan.

    Measured: Baseline,one year

  6. Percentage Change in Total Hip Bone Mineral Density

    Percentage change of Bone Mineral Density after one year of treatment from baseline.

    Measured with Dual-energy X-ray absorptiometry (DXA)-scan.

    Measured: Baseline,one year

  7. Percentage Change in Femoral Neck Bone Mineral Density

    Percentage change of Bone Mineral Density after one year of treatment from baseline.

    Measured with Dual-energy X-ray absorptiometry (DXA)-scan.

    Measured: Baseline,one year

  8. Percentage Change in 1/3 Forearm Bone Mineral Density

    Percentage change of Bone Mineral Density after one year of treatment from baseline.

    Measured with Dual-energy X-ray absorptiometry (DXA)-scan.

    Measured: Baseline,one year

Secondary outcomes (26)
  1. Change in Volumetric BMD for the Lumbar Spine.

    Measured at baseline and after one year by QCT.

    Measured: Baseline, one year

  2. Mean P-calcium During Treatment.

    Blood samples were acquired once every 4 weeks for safety-purposes.

    Measured: Monthly up to one year.

  3. Percent Change From Baseline in P-carboxy-terminal Collagen Crosslinks (CTX)

    p-CTX, change from baseline at 48 weeks.

    Measured: Change from baseline at 48 weeks reported.

  4. Median Agatstons Score Final

    Simultaneously with QCT-measurements coronary calcification was be assessed. Agatston score is a score based on the extent of coronary artery calcification calculated on the amount of plaque observed in a CT scan. A score of zero indicates absence of coronary calcium, 1-10: minimal calcification, 11-100 mild calcification, 101-400 moderate calcification, >400 severe calcification.

    Thus the score increases with increasing level of calcification in the coronary vessels.

    Measured: Baseline, one year

  5. Patients With Nephrolithiasis Final Scan.

    Number of subjects w. renal stones at final scan.

    Measured: Patients with nephrolithiasis at one year reported.

  6. Patients With Pancreas-calcifications Final Scan.

    By QCT.

    Measured: Patients with pancreas-calcifications at one year reported.

  7. Reset of the Calcium Sensing Receptor?

    Measured from effect on s-calcium and PTH weeks after termination of IMP

    Measured: 2 weeks after termination of medication.

  8. Vertebral Fracture Assessment - Final Scan

    Number of participants with vertebral fractures as assessed by VFA at final scan.

    Measured: Patients with vertebral fractures at one year reported.

  9. Change MDI-score

    Major Depression Inventory (MDI)-score, Baseline, 6 months, one year (week 52)., change between baseline and 1 year reported.

    The Major Depression Inventory (MDI) is a mood questionnaire developed by the World Health Organization. To calculate the total score, a sum of ten individual items (each with an individual score between 0-5, with 0 indicating absence of a symptom and 5 indicating constant presence of a given symptom) is used. A higher score signifies deeper depression with 50 being the maximum score.

    Measured: Baseline, 6 mths, one year.

  10. Adverse Reactions.

    All participants filled in questionnaires regarding symptoms related to the treatment.

    Results are reported in the Adverse Events section.

    Measured: Monthly up to one year.

  11. Bone Mineral Content

    Measured at baseline and after one year at the lumbar spine and distal 1/3 of the non-dominant antebrachii.

    Measured: Baseline, one year

  12. Change in Cortical Width.

    Measured at baseline and after one year at the distal non-dominant antebrachii.

    Measured: Baseline, one year.

  13. Change in Volumetric BMD for the Distal Forearm.

    Measured at baseline and after one year by QCT.

    Measured: Baseline, one year

  14. Percentage Change in Volumetric BMD for the Lumbar Spine.

    Measured at baseline and after one year by QCT.

    Measured: Baseline, one year

  15. Percentage Change in Volumetric BMD for the Distal Forearm.

    Measured at baseline and after one year by QCT.

    Measured: Baseline, one year

  16. Mean p-PTH During Treatment.

    Blood samples were acquired once every 4 weeks for safety-purposes.

    Measured: Monthly up to one year.

  17. Mean p-Phosphate During Treatment.

    Blood samples were acquired once every 4 weeks for safety-purposes.

    Measured: Monthly up to one year.

  18. Percent Change From Baseline in p-N-terminal Propeptide of Type I Procollagen (p-P1NP).

    p-P1NP, change from baseline at 48 weeks.

    Measured: Change from baseline at 48 weeks reported.

  19. Percent Change From Baseline in P-osteocalcin.

    p-osteocalcin, change from baseline at 48 weeks.

    Measured: Change from baseline at 48 weeks reported.

  20. Percent Change From Baseline in S-bone-specific Alkaline Phosphatase (BAP).

    S-Bone specific alkaline phosphatase, change from baseline at 48 weeks.

    Measured: Change from baseline at 48 weeks reported.

  21. Percent Change From Baseline in p-Tartrate-resistant Acid Phosphatase 5b (Trap5b).

    P-Trap5b, change from baseline at 48 weeks.

    Measured: Change from baseline at 48 weeks reported.

  22. Percent Change From Baseline in p-Sclerostin.

    P-Sclerostin, change from baseline at 48 weeks.

    Measured: Change from baseline at 48 weeks reported.

  23. Percent Change From Baseline in P-fibroblast Growth Factor 23 (FGF23).

    P-FGF23 , change from baseline at 48 weeks.

    Measured: Change from baseline at 48 weeks reported.

  24. Changes in p-25-vitamin D

    P-25-vitD , change from baseline at 48 weeks.

    Measured: Change from baseline at 48 weeks reported.

  25. Changes in s-1,25-vitamin D

    S-1,25-vitD, change from baseline at 48 weeks.

    Measured: Change from baseline at 48 weeks reported.

  26. Patients With Nephrocalcinosis, Final Scan.

    Number of subjects w. renal calcifications at final scan.

    Measured: Baseline, one year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Jan 2017 (estimated)
  2. Study start1 Mar 2017
  3. Primary completion1 Apr 2019
  4. Study completion12 Sep 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
46 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03027557
Sponsor's protocol ID
180987
Other IDs
2016-001510-20, 2016
Acronym
DENOCINA
Status last verified
May 2021
First submitted
16 Jan 2017
Last updated
25 May 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Leere JS, Karmisholt J, Robaczyk M, Lykkeboe S, Handberg A, Steinkohl E, Brondum Frokjaer J, Vestergaard P. Denosumab and cinacalcet for primary hyperparathyroidism (DENOCINA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Diabetes Endocrinol. 2020 May;8(5):407-417. doi: 10.1016/S2213-8587(20)30063-2.

    PubMed 32333877

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Cinacalcet 30 mg Tablet and Denosumab Inj 60 mg/ml in people with Primary Hyperparathyroidism and Parathyroid Adenoma, run by Peter Vestergaard at 1 site in Denmark.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 May 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Lumbar Spine Bone Mineral Density (time frame: Baseline,one year). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03027557, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 May 2021.

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