Primary HyperparathyroidismPhase 2/3NCT02525796
Evaluating Alternative Medical Therapies in Primary Hyperparathyroidism
A Phase 2/3 study testing eplerenone, amiloride and Cinacalcet in people with Primary Hyperparathyroidism, run by Brigham and Women's Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Primary Hyperparathyroidism
- What is being tested?
- eplerenone, amiloride and Cinacalcet
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 69 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2016to 2 Oct 2021
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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 locations and contacts
1 site in 1 country.
United States1 site
Brigham and Women's Hospital
Boston, Massachusetts, 02115
About this study
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.
Read the 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.
- Conditions
- Primary Hyperparathyroidism
- Being tested
- eplerenone, amiloride, Placebo, Cinacalcet
- Medical subject headings
- Hyperparathyroidism, Primary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
eplerenoneDrug
eplerenone, titrated up to a maximum of 50mg BID
amilorideDrug
amiloride, titrated up to a maximum of 10mg BID
PlaceboDrug
CinacalcetDrug
Cinacalcet, as add-on therapy in addition to eplerenone/amiloride/placebo, titrated up to a maximum of 30mg BID
| Study group | Role | What they receive |
|---|---|---|
| Placebo + Cinacalcet | Placebo comparator | Patients with primary hyperparathyroidism will receive placebo for 4 weeks followed by the addition of cinacalcet for 2 weeks Receives: Drug: Placebo; Drug: Cinacalcet |
| Amiloride + Cinacalcet | Active comparator | Patients with primary hyperparathyroidism will receive amiloride for 4 weeks followed by the addition of cinacalcet for 2 weeks Receives: Drug: amiloride; Drug: Cinacalcet |
| Eplerenone + Cinacalcet | Experimental | Patients with primary hyperparathyroidism will receive eplerenone for 4 weeks followed by the addition of cinacalcet for 2 weeks Receives: Drug: eplerenone; Drug: Cinacalcet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Parathyroid Hormone Levels
Change in circulating PTH levels before and after 4 weeks of double-blinded intervention when compared to placebo
Measured: 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 (1)
Change in Calcium Levels
Change in serum calcium levels before and after intervention when compared to placebo
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2015 (estimated)
- Study startJan 2016
- Primary completion1 Oct 2021
- Study completion2 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Primary HyperparathyroidismStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 69 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Anand Vaidya, Brigham and Women's Hospital
- Investigators
- Anand Vaidya, MD MMSc, Principal investigator, Brigham and Women's Hospital, Harvard Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02525796
- Sponsor's protocol ID
- 107407
- Status last verified
- Apr 2023
- First submitted
- 14 Aug 2015
- Last updated
- 3 May 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- 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
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating Alternative Medical Therapies in Primary Hyperparathyroidism
- ClinicalTrials.gov ID
- NCT02525796
- Acronym / sponsor ID
- 107407
- Conditions
- Primary Hyperparathyroidism
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 69 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Study start
- Jan 2016 (actual)
- Primary completion
- 1 Oct 2021 (actual)
- Study completion
- 2 Oct 2021 (actual)
- First posted
- 17 Aug 2015 (estimated)
- Results
- Posted 3 May 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- 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.
| Arm | Type | Receives |
|---|---|---|
| Placebo + Cinacalcet | Placebo comparator | Drug: Placebo, Drug: CinacalcetPatients with primary hyperparathyroidism will receive placebo for 4 weeks followed by the addition of cinacalcet for 2 weeks |
| Amiloride + Cinacalcet | Active comparator | Drug: amiloride, Drug: CinacalcetPatients with primary hyperparathyroidism will receive amiloride for 4 weeks followed by the addition of cinacalcet for 2 weeks |
| Eplerenone + Cinacalcet | Experimental | Drug: eplerenone, Drug: CinacalcetPatients with primary hyperparathyroidism will receive eplerenone for 4 weeks followed by the addition of cinacalcet for 2 weeks |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| eplerenoneeplerenone, titrated up to a maximum of 50mg BID | Drug | Eplerenone + Cinacalcet |
| amilorideamiloride, titrated up to a maximum of 10mg BID | Drug | Amiloride + Cinacalcet |
| Placebo | Drug | Placebo + Cinacalcet |
| CinacalcetCinacalcet, as add-on therapy in addition to eplerenone/amiloride/placebo, titrated up to a maximum of 30mg BID | Drug | Amiloride + Cinacalcet, Eplerenone + Cinacalcet, Placebo + Cinacalcet |
Primary outcome
Change in Parathyroid Hormone Levels
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 circulating PTH levels before and after 4 weeks of double-blinded intervention when compared to placebo
1 secondary outcome
Change in Calcium Levels
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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anand Vaidya, MD MMSc principal investigator
Brigham and Women's Hospital, Harvard Medical School
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing eplerenone, amiloride and Cinacalcet in people with Primary Hyperparathyroidism, run by Brigham and Women's Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 May 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Parathyroid Hormone Levels (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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 May 2023.