Calcitonin for Primary Hyperparathyroidism

Overseen By Dawn Muskiewicz, MS

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Joseph Sferra

Must not be taking: Calcium channel blockers, Lithium

Disqualifiers: Neck surgery, Hypocalcemia, Vitamin D deficiency, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1 week

37 Participants Needed

Trial Summary

What is the purpose of this trial?

Patients with biochemically confirmed primary hyperparathyroidism and non-localizing SPECT-CT exam within the past year will be included. Subjects will be treated with calcitonin to lower calcium levels immediately prior to reimaging. The goal of this study is to determine whether lowering calcium will improve uptake/retention of sestamibi and improve sensitivity of SPECT-CT to localize parathyroid adenoma.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does require that if you are on thyroid medication or thiazide diuretics, you must have been taking them at the time of your initial scan and continue through the research scan. If you are currently taking calcium channel blockers, you may not be eligible to participate.

Is calcitonin safe for treating primary hyperparathyroidism?

While calcitonin itself is not directly mentioned, similar treatments like cinacalcet have been used for primary hyperparathyroidism. Cinacalcet is generally considered safe, but it can cause side effects like nausea, appetite loss, and hypocalcemia (low calcium levels in the blood). ^{1 2 3 4 5}

How does the drug Calcitonin differ from other treatments for primary hyperparathyroidism?

Calcitonin is unique because it is a hormone that helps regulate calcium levels in the body, and it is typically administered as a nasal spray or injection, unlike other treatments like cinacalcet, which is taken orally. While cinacalcet works by increasing the sensitivity of the parathyroid glands to calcium, calcitonin directly lowers blood calcium levels, offering a different approach to managing the condition. ^{4 6 7 8 9}

Research Team

Joseph Sferra, MD

Principal Investigator

University of Toledo College of Medicine

Eligibility Criteria

This trial is for patients with primary hyperparathyroidism who have high calcium levels and had a non-conclusive SPECT-CT scan in the last year. They should want surgery to treat their condition, be able to take calcitonin without health risks, and agree to a second SPECT-CT scan for research.

Inclusion Criteria

I want surgery for my primary hyperparathyroidism.

I am not allergic or sensitive to 99mTC-Sestamibi.

I can safely receive calcitonin treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are treated with calcitonin 200IU 2x per day for 2 days, then 1x on the day of SPECT-CT imaging to lower calcium levels prior to reimaging

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment, including conversion rate from non-localizing to localizing exam

1 year

Treatment Details

Interventions

• Calcitonin

Trial Overview The study tests if giving calcitonin, which lowers calcium levels, before re-imaging can improve the detection of parathyroid adenoma using SPECT-CT by enhancing sestamibi uptake/retention.

Participant Groups

Group I: Treatment Group Experimental Treatment 1 Intervention

All subjects in this arm will be treated with calcitonin 200IU 2x per day for 2 days, then 1x on day of SPECT-CT imaging

Calcitonin is already approved in United States, European Union for the following indications:

Approved in United States as Miacalcin for:

• Postmenopausal osteoporosis
• Paget's disease of bone
• Hypercalcemia

Approved in European Union as Miacalcin for:

• Postmenopausal osteoporosis
• Paget's disease of bone
• Hypercalcemia

Who Is Running the Clinical Trial?

Joseph Sferra

Lead Sponsor

Trials

1

Recruited

40+

ProMedica Health System

Lead Sponsor

Trials

14

Recruited

760+

University of Toledo Health Science Campus

Collaborator

Trials

42

Recruited

16,100+

Findings from Research

A novel calcimimetic drug was successfully used to treat a 78-year-old man with parathyroid carcinoma, effectively reducing his hypercalcemia and elevated PTH levels after conventional therapies failed.

The patient has been on calcimimetic monotherapy for over 600 days without any adverse effects, demonstrating its long-term safety and efficacy in managing hypercalcemia associated with parathyroid carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of hypercalcemia secondary to parathyroid carcinoma with a novel calcimimetic agent. Collins, MT., Skarulis, MC., Bilezikian, JP., et al.[2016]

Cinacalcet effectively reduces serum calcium and intact PTH levels in patients with primary hyperparathyroidism (PHPT), demonstrating its efficacy as a treatment option for hypercalcemia in 61 patients studied from 2014 to 2017.

While cinacalcet improves hypercalcemia, it is associated with gastrointestinal side effects in about 10% of patients, leading to some discontinuations and switches to surgical treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of cinacalcet for primary hyperparathyroidism: a single center experience. Manaka, K., Sato, J., Kinoshita, Y., et al.[2020]

Calcimimetics, which stimulate the calcium sensing receptor (RCa) or enhance its sensitivity, can effectively lower parathyroid hormone (PTH) levels and stimulate calcitonin secretion, making them a potential treatment for disorders like secondary hyperparathyroidism.

The first-generation calcimimetics showed efficacy in reducing PTH levels in uremic patients, but their low bioavailability limits clinical use; however, promising results from a second-generation calcimimetic, AMG-073, suggest better potential for long-term treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Parathyroid gland, calcium receptor and calcimimetics]. Ureña, P.[2018]

The calcimimetic NPS R-568 effectively prevents parathyroid hyperplasia and maintains serum PTH levels in rats with chronic renal insufficiency and severe secondary hyperparathyroidism, indicating its potential as a therapeutic intervention.

Both continuous infusion and high-dose daily gavage of NPS R-568 completely stopped the increase in parathyroid cell numbers, suggesting that it plays a crucial role in regulating parathyroid cell proliferation through calcium receptor activation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Calcimimetic NPS R-568 prevents parathyroid hyperplasia in rats with severe secondary hyperparathyroidism. Wada, M., Nagano, N., Furuya, Y., et al.[2016]

Cinacalcet is a safe and effective treatment for hypercalcemia in patients with primary hyperparathyroidism who cannot have surgery, but it can lead to significant side effects like hypocalcemia.

This case report describes the first known instance of parathyroid apoplexy associated with cinacalcet treatment, highlighting the need for careful monitoring of patients on this medication, especially after reaching higher doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parathyroid Apoplexy Following Cinacalcet Treatment in Primary Hyperparathyroidism. Di Dalmazi, G., Giuliani, C., Napolitano, G.[2020]

Cinacalcet hydrochloride is an effective treatment for patients with chronic kidney disease on dialysis, significantly reducing parathyroid hormone (PTH) levels in a large study of 1136 participants over 26 weeks, regardless of various patient factors.

The treatment was well tolerated, with most side effects being mild to moderate, and it also effectively lowered serum calcium and phosphorus levels, indicating its potential for managing secondary hyperparathyroidism in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cinacalcet hydrochloride. Barman Balfour, JA., Scott, LJ.[2018]

Cinacalcet is an effective calcimimetic that lowers parathyroid hormone (PTH) levels and helps manage secondary hyperparathyroidism in patients undergoing dialysis for chronic kidney disease, improving adherence to mineral guidelines set by the National Kidney Foundation.

It is also approved for treating hypercalcemia in patients with inoperable parathyroid carcinoma, providing a new medical option for lowering serum calcium, although its long-term effects on prognosis remain uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical utility of calcimimetics targeting the extracellular calcium-sensing receptor (CaSR). Brown, EM.[2018]

Cinacalcet is an effective treatment for secondary hyperparathyroidism in dialysis patients, significantly lowering plasma parathyroid hormone levels, and can be used alone or in combination with vitamin D.

Unlike vitamin D sterols, cinacalcet does not raise serum calcium and phosphorus levels, and it may also help reduce parathyroid gland hyperplasia and increase bone mass, suggesting additional benefits for long-term management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Calcimimetics: a remedy for all problems of excess parathyroid hormone activity in chronic kidney disease? Goodman, WG.[2019]

In a study of nine patients with primary hyperparathyroidism (PHPT) due to parathyroid adenomas, cinacalcet treatment for 6 months resulted in a significant 29% reduction in the size of the adenomas, demonstrating its efficacy in this condition.

The reduction in adenoma size was positively correlated with the serum levels of intact parathyroid hormone (PTH) before treatment, suggesting that higher PTH levels may predict a better response to cinacalcet therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduction in parathyroid adenomas by cinacalcet therapy in patients with primary hyperparathyroidism. Minezaki, M., Takashi, Y., Ochi, K., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Treatment of hypercalcemia secondary to parathyroid carcinoma with a novel calcimimetic agent. [2016]

2. Japan pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of cinacalcet for primary hyperparathyroidism: a single center experience. [2020]

3. Switzerland pubmed.ncbi.nlm.nih.gov

[Parathyroid gland, calcium receptor and calcimimetics]. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Calcimimetic NPS R-568 prevents parathyroid hyperplasia in rats with severe secondary hyperparathyroidism. [2016]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Parathyroid Apoplexy Following Cinacalcet Treatment in Primary Hyperparathyroidism. [2020]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Cinacalcet hydrochloride. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Clinical utility of calcimimetics targeting the extracellular calcium-sensing receptor (CaSR). [2018]

8. England pubmed.ncbi.nlm.nih.gov

Calcimimetics: a remedy for all problems of excess parathyroid hormone activity in chronic kidney disease? [2019]

9. Japan pubmed.ncbi.nlm.nih.gov

Reduction in parathyroid adenomas by cinacalcet therapy in patients with primary hyperparathyroidism. [2021]