Evaluating Alternative Medical Therapies in Primary Hyperparathyroidism

Sponsor

Brigham and Women's Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT02525796

Collaborator

(none)

Enrollment

Location

Arms

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Primary Hyperparathyroidism	Drug: eplerenone Drug: amiloride Drug: Placebo Drug: Cinacalcet	Phase 2/Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

69 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Evaluating Alternative Medical Therapies in Primary Hyperparathyroidism

Actual Study Start Date :

Jan 1, 2016

Actual Primary Completion Date :

Oct 1, 2021

Actual Study Completion Date :

Oct 2, 2021

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo + Cinacalcet Patients with primary hyperparathyroidism will receive placebo for 4 weeks followed by the addition of cinacalcet for 2 weeks	Drug: Placebo Drug: Cinacalcet Cinacalcet, as add-on therapy in addition to eplerenone/amiloride/placebo, titrated up to a maximum of 30mg BID
Active Comparator: Amiloride + Cinacalcet Patients with primary hyperparathyroidism will receive amiloride for 4 weeks followed by the addition of cinacalcet for 2 weeks	Drug: amiloride amiloride, titrated up to a maximum of 10mg BID Drug: Cinacalcet Cinacalcet, as add-on therapy in addition to eplerenone/amiloride/placebo, titrated up to a maximum of 30mg BID
Experimental: Eplerenone + Cinacalcet Patients with primary hyperparathyroidism will receive eplerenone for 4 weeks followed by the addition of cinacalcet for 2 weeks	Drug: eplerenone eplerenone, titrated up to a maximum of 50mg BID Drug: Cinacalcet Cinacalcet, as add-on therapy in addition to eplerenone/amiloride/placebo, titrated up to a maximum of 30mg BID

Arm

Intervention/Treatment

Placebo Comparator: Placebo + Cinacalcet

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

Drug: Placebo

Drug: Cinacalcet

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

Active Comparator: Amiloride + Cinacalcet

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

Drug: amiloride

amiloride, titrated up to a maximum of 10mg BID

Drug: Cinacalcet

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

Experimental: Eplerenone + Cinacalcet

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

Drug: eplerenone

eplerenone, titrated up to a maximum of 50mg BID

Drug: Cinacalcet

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

Outcome Measures

Primary Outcome Measures

Change in parathyroid hormone levels [4 weeks]
Change in circulating PTH levels before and after intervention when compared to placebo

Secondary Outcome Measures

Change in calcium levels [4 weeks]
Change in serum calcium levels before and after intervention when compared to placebo

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

Brigham and Women's Hospital

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Anand Vaidya, Assistant Professor of Medicine, Harvard Medical School, Brigham and Women's Hospital

ClinicalTrials.gov Identifier:

NCT02525796

Other Study ID Numbers:

107407

First Posted:

Aug 17, 2015

Last Update Posted:

Nov 29, 2021

Last Verified:

Nov 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Additional relevant MeSH terms:

Hyperparathyroidism

Hyperparathyroidism, Primary

Eplerenone

Amiloride

Cinacalcet

Study Results

No Results Posted as of Nov 29, 2021