Clinical trial NCT02525796: Evaluating Alternative Medical Therapies in Primary Hyperparathyroidism
Official title: Evaluating Alternative Medical Therapies in Primary Hyperparathyroidism
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Primary Hyperparathyroidism
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2015-08-17
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 3-parallel-armed double-blinded randomized controlled trial wherein monotherapy of eplerenone or amiloride or placebo administered for 4 weeks. After weeks, an open-label extension addition of cinacalcet to all 3 arms conducted for 2 weeks.
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change in Parathyroid Hormone Levels
timeFrame: 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 outcomes:
measure: Change in Calcium Levels
timeFrame: 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)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital, Harvard Medical School
name: Anand Vaidya, MD MMSc
role: PRINCIPAL_INVESTIGATOR
References: