Boston, Massachusetts 02115


Purpose:

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.


Study summary:

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.


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.


NCT ID:

NCT02525796


Primary Contact:

Principal Investigator
Anand Vaidya, MD MMSc
Brigham and Women's Hospital, Harvard Medical School

Anand Vaidya, MD MMSc
Phone: 617-525-8285


Backup Contact:

Molly Connors
Phone: 617-732-5186


Location Contact:

Boston, Massachusetts 02115
United States

Molly Connors
Phone: 617-732-5186

Site Status: Recruiting


Data Source: ClinicalTrials.gov

Date Processed: November 23, 2017

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