Evaluating Alternative Medical Therapies in Primary Hyperparathyroidism

Primary Hyperparathyroidism Clinical Trial

Official title:

Evaluating Alternative Medical Therapies in Primary Hyperparathyroidism

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02525796
• Other study ID #: 107407
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: January 2016
• Est. completion date: October 2, 2021

Study information

• Verified date: April 2023
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate whether blocking the mineralocorticoid receptor, alone, or in combination with the calcimimetic cinacalcet, can lower parathyroid hormone and calcium levels in primary hyperparathyroidism.

Description:

To conduct a double-blinded, placebo-controlled, randomized intervention study to investigate whether mineralocorticoid receptor (MR) antagonism, alone or in combination with cinacalcet, is an effective therapy for primary hyperparathyroidism (P-HPTH).

Hypothesis: MR antagonism, as a monotherapy or in combination with a calcimimetic, is a mechanism to lower parathyroid hormone (PTH) in primary hyperparathyroidism (P-HPTH).

Study Design: Sixty subjects with P-HPTH will be enrolled to randomly receive eplerenone (a potassium-sparing diuretic that directly blocks the MR), amiloride (a potassium-sparing diuretic that does not directly block the MR), or placebo for 4 weeks. Thereafter, all subjects will receive cinacalcet therapy (a calcimimetic that lowers PTH) in addition to their randomized intervention for an additional 2 weeks.

Anticipated Results: In this proof-of-concept study, eplerenone therapy will lower PTH, serum calcium, and markers of bone resorption in P-HPTH, when compared to placebo. The PTH response to amiloride will resemble that of placebo, suggesting that the eplerenone mediated reductions in PTH are specific to interactions with the MR. Combination therapy with eplerenone + cinacalcet will result in additive or synergistic reductions in PTH, when compared to placebo + cinacalcet or placebo + amiloride.

Implications: MR antagonism (alone or in combination with cinacalcet) may be a mechanism to lower PTH and calcium in P-HPTH, thereby identifying a new potential option in the limited medical therapies for P-HPTH.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 69
• Est. completion date: October 2, 2021
• Est. primary completion date: October 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• physician diagnosis of active P-HPTH (Serum calcium > upper limit of reference range and serum PTH > ULRR; or Serum Calcium > ULRR AND serum PTH > 30 pg/mL; or Serum Calcium within 0.2 mg/dL of the ULRR and PTH>ULRR).

• negative pregnancy test in women aged 18-45

Exclusion Criteria:

• estimated glomerular filtration rate < 60mL/min/1,73m2

• serum potassium > 5.0 mmol/L

• age <18 or >80 years

• diabetes that is not well controlled (HbA1c>8%)\

• liver failure

• heart failure

• history of myocardial infarction or stroke

• active use of lithium

• active chronic inflammatory conditions (such as inflammatory bowel disease, rheumatoid arthritis, sarcoidosis)

• initiation within 3 months of bisphosphonates or cinacalcet

• need for imminent parathyroidectomy (within the next 6-8 weeks) as determined by their endocrinologist or surgeon

• absolute serum calcium >13.0 mg/dL

• positive pregnancy test on any of the study visits for women ages 18-45.

Related Conditions & MeSH terms

• Hyperparathyroidism
• Hyperparathyroidism, Primary
• Primary Hyperparathyroidism

Intervention

Drug:
• eplerenone
eplerenone, titrated up to a maximum of 50mg BID
• amiloride
amiloride, titrated up to a maximum of 10mg BID
• Placebo

• Cinacalcet
Cinacalcet, as add-on therapy in addition to eplerenone/amiloride/placebo, titrated up to a maximum of 30mg BID

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Brigham and Women's Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Parathyroid Hormone Levels	Change in circulating PTH levels before and after 4 weeks of double-blinded intervention when compared to placebo	Change in circulating PTH levels before and after 4 weeks of double-blinded monotherapy intervention when compared to placebo (PTH at 4 weeks minus PTH at baseline)
Secondary	Change in Calcium Levels	Change in serum calcium levels before and after intervention when compared to placebo	Change in serum calcium levels before and after 4 weeks of double-blinded monotherapy intervention when compared to placebo (calcium at 4 weeks minus calcium at baseline)