Evaluating Alternative Medical Therapies in Primary Hyperparathyroidism

Mass General Brigham

Status and phase: Completed; Phase 3; Phase 2

Conditions: Primary Hyperparathyroidism

Treatments: Drug: eplerenone; Drug: amiloride; Drug: Placebo; Drug: Cinacalcet

Study type: Interventional

Funder types: Other

Identifiers

NCT02525796

107407

Details and patient eligibility

About

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.

Full 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.

Enrollment: 69 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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69 participants in 3 patient groups, including a placebo group

Placebo + Cinacalcet

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

Drug: Cinacalcet

Amiloride + Cinacalcet

Active Comparator group

Description:

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

Treatment:

Drug: amiloride

Drug: Cinacalcet

Eplerenone + Cinacalcet

Experimental group

Description:

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

Treatment:

Drug: eplerenone

Drug: Cinacalcet