A Phase 2/3 interventional study of eplerenone and amiloride in Primary Hyperparathyroidism, sponsored by Brigham and Women's Hospital. Completed at 1 site in United States. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2023-05-03.
Sponsored by Brigham and Women's Hospital · Phase 2/3, Interventional, and Treatment
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.
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.
104 studies on the registry are indexed under Hyperparathyroidism, Primary; 23 are open to participants now.
This study's enrollment of 69 is close to the median of 68 across 60 interventional studies indexed under Hyperparathyroidism, Primary.
Browse Hyperparathyroidism, Primary studies →Brigham and Women's Hospital is the lead sponsor of 1,267 studies on the registry; 228 are open to participants now.
Of its 116 completed or terminated interventional studies of FDA-regulated products, 65 (56%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HbA1c
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients with primary hyperparathyroidism will receive placebo for 4 weeks followed by the addition of cinacalcet for 2 weeks
Drug: Placebo · Drug: Cinacalcet
Patients with primary hyperparathyroidism will receive amiloride for 4 weeks followed by the addition of cinacalcet for 2 weeks
Drug: amiloride · Drug: Cinacalcet
Patients with primary hyperparathyroidism will receive eplerenone for 4 weeks followed by the addition of cinacalcet for 2 weeks
Drug: eplerenone · Drug: Cinacalcet
eplerenone, titrated up to a maximum of 50mg BID
amiloride, titrated up to a maximum of 10mg BID
Cinacalcet, as add-on therapy in addition to eplerenone/amiloride/placebo, titrated up to a maximum of 30mg BID
Change in Parathyroid Hormone Levels
Change in circulating PTH levels before and after 4 weeks of double-blinded intervention when compared to placebo
Time frame: 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)
Change in Calcium Levels
Change in serum calcium levels before and after intervention when compared to placebo
Time frame: 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)
| Milestone | Eplerenone | Amiloride | Placebo |
|---|---|---|---|
| Started | 14 | 14 | 13 |
| Completed | 12 | 12 | 12 |
| Not completed | 2 | 2 | 1 |
| Withdrew: Adverse event | 1 | 1 | 1 |
| Withdrew: Lost to follow-up | 1 | 0 | 0 |
| Withdrew: Physician decision | 0 | 1 | 0 |
| Milestone | Eplerenone | Amiloride | Placebo |
|---|---|---|---|
| Started | 12 | 12 | 12 |
| Open-label cinacalcet | 12 | 12 | 12 |
| Completed | 8 | 10 | 9 |
| Not completed | 4 | 2 | 3 |
| Withdrew: Withdrawal by subject | 2 | 0 | 1 |
| Withdrew: Adverse event | 2 | 2 | 2 |
Change in circulating PTH levels before and after 4 weeks of double-blinded intervention when compared to placebo
| pg/mL | Eplerenone | Amiloride | Placebo |
|---|---|---|---|
| Change in Parathyroid Hormone Levels | 4.0 (-10.4 to 10.4) | -3.7 (-11.4 to 8.7) | 0.8 (-3.6 to 8.3) |
Change in serum calcium levels before and after intervention when compared to placebo
| mg/dL | Eplerenone | Amiloride | Placebo |
|---|---|---|---|
| Change in Calcium Levels | 0.1 (-0.1 to 03) | 0.0 (-0.3 to 0.1) | 0.1 (-0.1 to 0.4) |
Collected over Over the course of the entire study, including the 4 week randomization to monotherapy (eplerenone vs amiloride vs placebo) and the 2 week open-label addition of cinacalcet (6 weeks in total).. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Eplerenone | 0/14 (0%) | 0/14 (0%) | 1/14 (7.1%) |
| Amiloride | 0/14 (0%) | 0/14 (0%) | 1/14 (7.1%) |
| Placebo | 0/13 (0%) | 0/13 (0%) | 1/13 (7.7%) |
| Eplerenone + Cinacalcet | 0/12 (0%) | 0/12 (0%) | 2/12 (16.7%) |
| Amiloride + Cinacalcet | 0/12 (0%) | 0/12 (0%) | 2/12 (16.7%) |
| Placebo + Cinacalcet | 0/12 (0%) | 0/12 (0%) | 2/12 (16.7%) |
| Event | Eplerenone | Amiloride | Placebo | Eplerenone + Cinacalcet | Amiloride + Cinacalcet | Placebo + Cinacalcet |
|---|---|---|---|---|---|---|
| low egfrRenal and urinary disorders | 0/14 | 0/14 | 1/13 | 1/12 | 0/12 | 0/12 |
| hyperkalemiaGeneral disorders | 1/14 | 1/14 | 0/13 | 0/12 | 1/12 | 1/12 |
| hypocalcemiaEndocrine disorders | 0/14 | 0/14 | 0/13 | 1/12 | 0/12 | 1/12 |
| low blood pressureCardiac disorders | 0/14 | 0/14 | 0/13 | 0/12 | 1/12 | 0/12 |
Patient with primary hyperparathyroidism
| Age, Categorical(Participants) | Eplerenone | Amiloride | Placebo | Total |
|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 7 | 9 | 3 | 19 |
| >=65 years | 7 | 5 | 10 | 22 |
| Age, Continuous(years) | Eplerenone | Amiloride | Placebo | Total |
|---|---|---|---|---|
| Mean | 65 ± 7 | 61 ± 9 | 69 ± 10 | 65 ± 9 |
| Sex: Female, Male(Participants) | Eplerenone | Amiloride | Placebo | Total |
|---|---|---|---|---|
| Female | 12 | 11 | 11 | 34 |
| Male | 2 | 3 | 2 | 7 |
| Race (NIH/OMB)(Participants) | Eplerenone | Amiloride | Placebo | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 |
| Black or African American | 0 | 5 | 1 | 6 |
| White | 12 | 7 | 12 | 31 |
| More than one race | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 2 | 2 | 0 | 4 |
| Region of Enrollment(participants) | Eplerenone | Amiloride | Placebo | Total |
|---|---|---|---|---|
| United States | 14 | 14 | 13 | 41 |
| Parathyroid hormone(pg/mL) | Eplerenone | Amiloride | Placebo | Total |
|---|---|---|---|---|
| Mean | 65 ± 17 | 89 ± 56 | 66 ± 26 | 74 ± 39 |
| Serum calcium(mg/dL) | Eplerenone | Amiloride | Placebo | Total |
|---|---|---|---|---|
| Mean | 10.4 ± 0.5 | 10.5 ± 0.5 | 10.4 ± 0.6 | 10.5 ± 0.5 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — IPD will be shared with interested investigators upon request 1 year after the study is completed. Investigators may request IPD by contacting the PI and proposing a data analysis plan
Ran from Jan 2016 to primary completion in Oct 2021, 69 months.
Results were first posted in May 2023, 1 year 7 months after primary completion.
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Studies of the drug tested here: Eplerenone
Hyperparathyroidism, Primary →
Brigham and Women's Hospital →