Evaluating Alternative Medical Therapies in Primary Hyperparathyroidism

NCT ID: NCT02525796

Last Updated: 2023-05-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 69 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-31
• Study Completion Date: 2021-10-02

Brief 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.

Detailed 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.

Conditions

Primary Hyperparathyroidism

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo + Cinacalcet

Patients with primary hyperparathyroidism will receive placebo for 4 weeks followed by the addition of cinacalcet for 2 weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Cinacalcet

Intervention Type: DRUG

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

Amiloride + Cinacalcet

Patients with primary hyperparathyroidism will receive amiloride for 4 weeks followed by the addition of cinacalcet for 2 weeks

Group Type: ACTIVE_COMPARATOR

amiloride

Intervention Type: DRUG

amiloride, titrated up to a maximum of 10mg BID

Cinacalcet

Intervention Type: DRUG

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

Eplerenone + Cinacalcet

Patients with primary hyperparathyroidism will receive eplerenone for 4 weeks followed by the addition of cinacalcet for 2 weeks

Group Type: EXPERIMENTAL

eplerenone

Intervention Type: DRUG

eplerenone, titrated up to a maximum of 50mg BID

Cinacalcet

Intervention Type: DRUG

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

Interventions

eplerenone

eplerenone, titrated up to a maximum of 50mg BID

Intervention Type: DRUG

amiloride

amiloride, titrated up to a maximum of 10mg BID

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Cinacalcet

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

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Anand Vaidya

Assistant Professor of Medicine, Harvard Medical School

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Anand Vaidya, MD MMSc

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital, Harvard Medical School

Locations

Brigham and Women's Hospital

Boston, Massachusetts, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

107407

Identifier Type: -

Identifier Source: org_study_id