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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests calcitonin (a hormone therapy) to improve the detection of problematic parathyroid glands in patients with primary hyperparathyroidism. The goal is to determine if lowering calcium levels with calcitonin before a SPECT-CT scan aids in identifying glands requiring treatment. Suitable candidates have primary hyperparathyroidism, have undergone a SPECT-CT scan with unclear results in the past year, and seek surgery for the condition. As a Phase 4 trial, this research aims to understand how the already FDA-approved and effective treatment benefits more patients.

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.

What is the safety track record for calcitonin?

Research has shown that calcitonin, a treatment tested to lower calcium levels in primary hyperparathyroidism, is generally well-tolerated. The FDA has approved calcitonin for other uses, indicating its safety. Most individuals experience only mild side effects, if any.

Since this trial is in a later stage, substantial evidence from earlier research supports calcitonin's safety. These earlier studies typically assess the treatment's safety and tolerability.

Overall, individuals using calcitonin report few side effects, which is encouraging for those considering participation in trials with this treatment. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Calcitonin is unique because it offers a different approach to managing primary hyperparathyroidism compared to standard treatments like surgery or medications that lower calcium levels. Most treatments for this condition focus on either removing the overactive glands or managing calcium levels indirectly. Calcitonin, however, directly targets the body's calcium regulation by inhibiting bone resorption, which may quickly reduce high calcium levels in the blood. Researchers are excited about calcitonin because its fast-acting nature could provide a rapid response, especially beneficial for patients needing quick relief from symptoms.

What evidence suggests that calcitonin might be an effective treatment for primary hyperparathyroidism?

Research has shown that calcitonin can help manage primary hyperparathyroidism by lowering high calcium levels in the blood. In this trial, all participants will receive calcitonin treatment. A new drug using calcitonin has effectively reduced high calcium levels in patients with parathyroid issues. Specifically, this method helped a patient with parathyroid cancer, suggesting its potential for similar conditions. Calcitonin works by directly lowering calcium levels, which is crucial for people with primary hyperparathyroidism. While further research is beneficial, current evidence supports calcitonin as a promising option for managing this condition. ^{1 2 6 7 8}

Who Is on the Research Team?

Joseph Sferra, MD

Principal Investigator

University of Toledo College of Medicine

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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 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]

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]

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]

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]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK441895/

Primary Hyperparathyroidism - StatPearls - NCBI Bookshelf [4][5][124] Long-term outcomes in patients with hyperparathyroidism who do not undergo surgery are reported for patients followed for as long as 15 years. [125 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7424342/

Cinacalcet and primary hyperparathyroidism While cinacalcet reduces circulating PTH levels, we found that there was a lack of change in the size of the parathyroid gland as reported in two studies.

3. academic.oup.com academic.oup.com/jbmr/article/37/11/2293/7512381

Evaluation and Management of Primary Hyperparathyroidism For patients with asymptomatic PHPT, PTX achieved a biochemical cure in 97.8% (high quality evidence for cure rate). This percentage is consistent with the ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S002235652446388X

Discovery of a Calcimimetic with Differential Effects on ... We found the new molecule effectively reduced PTH levels without promoting calcitonin secretion or hypocalcemia. Furthermore, our third-generation molecule was ...

5. withpower.com withpower.com/trial/phase-4-hyperparathyroidism-primary-4-2019-8c976

Calcitonin for Primary Hyperparathyroidism A novel calcimimetic drug was successfully used to treat a 78-year-old man with parathyroid carcinoma, effectively reducing his hypercalcemia and elevated PTH ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03774771?term=AREA%5BBasicSearch%5D(AREA%5BInterventionSearch%5D(CINACALCET)%20AND%20AREA%5BStudyType%5D(INTERVENTIONAL))&rank=9

Safety, Pharmacokinetics, and Clinical Effects of Cinacalcet ... The primary objective was to assess the safety and tolerability of cinacalcet in adults with primary hyperparathyroidism (HPT) when administered as a single ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1530891X24003963

#1706317 A case of Primary Hyperparathyroidism ... The initial workup showed elevated WBCs 21,000 k/cmm, elevated calcium14 mg/dl, albumin 2.6 gm/dl,PTH 33, and GFR 37 ml/min/1.73 m2. Renal ultrasound confirmed ...

8. ec.bioscientifica.com ec.bioscientifica.com/view/journals/ec/9/7/EC-20-0221.xml

Cinacalcet and primary hyperparathyroidism The results from the meta-analysis support the use of cinacalcet as an alternative or bridging therapy to treat hypercalcemia in people with PHPT.