Healthy VolunteersPhase 1NCT02871648
The Role of Minerelocorticoid Receptor on Modulating Aldosterone Production
A Phase 1 study testing Fludrocortisone and Eplerenone in people with Healthy Volunteers, run by Brigham and Women's Hospital at 1 site in United States.
Trial summary
The purpose of this research protocol is to determine if the same effects are observed in vivo in humans using a similar approach. Demonstrating that mineralocorticoid acts on zona glomerulosa cells to regulate aldosterone production in a short feedback loop would provide important insight into hormone regulation, and… Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- Fludrocortisone and Eplerenone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2016to Dec 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Participants must be healthy, with no prior history of hypertension, no family history of hypertension, diabetes, stroke or cardiac disease in first-degree relatives before the age of 70 years and have an average (two measurements) blood pressure of <130/89 mm Hg and >100/50 mmHg at the screening visit.
- All subjects will have body mass index 19-25 kg/m2.
- Subjects must have normal laboratory values for: Complete blood count; serum creatinine, sodium, potassium, glucose, liver enzymes; urinalysis; negative urine HCG in women; normal ECG
Who cannot join
- Alcohol intake >12oz per week, as well as tobacco or recreational drug use.
- Any subject with a history of coronary disease, diabetes, hypertension, stroke, kidney disease, or illness requiring overnight hospitalization in the past 6 months will be excluded from the study.
- Subjects taking any prescription medications (with the exception of birth control pills) or herbal medications will be excluded.
- Because of the unknown risk of infused angiotensin II in pregnancy, women who are pregnant will be excluded from study and all women will be screened for pregnancy by quantitative serum hCG measurement on the day of each CCI admission.
- Women currently breastfeeding will also be excluded from the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
Brigham and Women's Hospital
Boston, Massachusetts, 02115
About this study
The purpose of this research protocol is to determine if the same effects are observed in vivo in humans using a similar approach. Demonstrating that mineralocorticoid acts on zona glomerulosa cells to regulate aldosterone production in a short feedback loop would provide important insight into hormone regulation, and explain variability in pathophysiologic states such as hypertension and cardiovascular diseases.
Read the detailed description
In order to provide additional evidence indicating the presence of functional and in order to provide additional evidence indicating the presence of functional mineralocorticoid receptors (MR) on zona glomerulosa (ZG) cells, the investigators propose the following protocol in healthy volunteers. The investigators will evaluate aldosterone and cortisol production in response to an angiotensin II infusion after three separate test conditions: 1) placebo, 2) following a single dose of fludrocortisone, and 3) following a single dose of eplerenone (a MR antagonist).
- Conditions
- Healthy Volunteers
- Being tested
- Placebo, Fludrocortisone, Eplerenone
- Keywords
- Healthy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Placebo prepared by Investigation Drug Services at Brigham and Women's Hospital
FludrocortisoneDrug
Also called Florinef
Fludrocortisone 0.1 mg
EplerenoneDrug
Also called Inspra
Epleronone 100 mg
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo prepared by Investigational Drug Services at Brigham and Women's Hospital Receives: Drug: Placebo |
| Fludrocortisone | Active comparator | Subjects will receive 0.1 mg of fludrocortisone (Florinef) on one of three study days. Receives: Drug: Fludrocortisone |
| Epleronone | Active comparator | Subjects will receive 100 mg of epleronone on one of three study days. Receives: Drug: Eplerenone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum aldosterone after angiotensin II infusion
Aldosterone levels after 30 mins AngII infusion
Measured: 5 days
Secondary outcomes (3)
Serum aldosterone after cosyntropin infusion
Aldosterone levels after 30 mins cosyntropin infusion
Measured: 5 days
Serum cortisol after angiotensin II infusion
Cortisol levels after 30 mins AngII infusion
Measured: 5 days
Serum cortisol after cosyntropin infusion
Cortisol levels after 30 mins cosyntropin infusion
Measured: 5 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2016 (estimated)
- Study startJan 2016
- Primary completionOct 2019
- Study completionDec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Healthy VolunteersStudies 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 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Gordon H. Williams, MD, Brigham and Women's Hospital
- Investigators
- Jonathan S Williams, MD, MMSc, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02871648
- Sponsor's protocol ID
- 2015P001664
- Status last verified
- Jun 2021
- First submitted
- 15 Aug 2016
- Last updated
- 8 Jun 2021
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Braley LM, Williams GH. Rat adrenal cell sensitivity to angiotensin II, alpha-1-24-ACTH, and potassium: a comparative study. Am J Physiol. 1977 Nov;233(5):E402-6. doi: 10.1152/ajpendo.1977.233.5.E402.
PubMed 200147Yuan YE, Adler GK, Rosner B, Merino AA, Guzelce EC, Williams GH, Williams JS, Haas AV. Investigating a Mineralocorticoid Receptor Mediation of an Ultra-Short Feedback Loop Regulating Aldosterone Production in Humans. Clin Endocrinol (Oxf). 2026 Aug 12. doi: 10.1111/cen.70189. Online ahead of print.
PubMed 42581762
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Minerelocorticoid Receptor on Modulating Aldosterone Production
- ClinicalTrials.gov ID
- NCT02871648
- Acronym / sponsor ID
- 2015P001664
- Conditions
- Healthy Volunteers
- Keywords
- Healthy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Study start
- Jan 2016
- Primary completion
- Oct 2019 (actual)
- Study completion
- Dec 2019 (actual)
- First posted
- 18 Aug 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this research protocol is to determine if the same effects are observed in vivo in humans using a similar approach. Demonstrating that mineralocorticoid acts on zona glomerulosa cells to regulate aldosterone production in a short feedback loop would provide important insight into hormone regulation, and explain variability in pathophysiologic states such as hypertension and cardiovascular diseases.
Detailed description
In order to provide additional evidence indicating the presence of functional and in order to provide additional evidence indicating the presence of functional mineralocorticoid receptors (MR) on zona glomerulosa (ZG) cells, the investigators propose the following protocol in healthy volunteers. The investigators will evaluate aldosterone and cortisol production in response to an angiotensin II infusion after three separate test conditions: 1) placebo, 2) following a single dose of fludrocortisone, and 3) following a single dose of eplerenone (a MR antagonist).
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboPlacebo prepared by Investigational Drug Services at Brigham and Women's Hospital |
| Fludrocortisone | Active comparator | Drug: FludrocortisoneSubjects will receive 0.1 mg of fludrocortisone (Florinef) on one of three study days. |
| Epleronone | Active comparator | Drug: EplerenoneSubjects will receive 100 mg of epleronone on one of three study days. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Participants must be healthy, with no prior history of hypertension, no family history of hypertension, diabetes, stroke or cardiac disease in first-degree relatives before the age of 70 years and have an average (two measurements) blood pressure of <130/89 mm Hg and >100/50 mmHg at the screening visit.
- All subjects will have body mass index 19-25 kg/m2.
- Subjects must have normal laboratory values for: Complete blood count; serum creatinine, sodium, potassium, glucose, liver enzymes; urinalysis; negative urine HCG in women; normal ECG
Key exclusion criteria (5 listed)
- Alcohol intake >12oz per week, as well as tobacco or recreational drug use.
- Any subject with a history of coronary disease, diabetes, hypertension, stroke, kidney disease, or illness requiring overnight hospitalization in the past 6 months will be excluded from the study.
- Subjects taking any prescription medications (with the exception of birth control pills) or herbal medications will be excluded.
- Because of the unknown risk of infused angiotensin II in pregnancy, women who are pregnant will be excluded from study and all women will be screened for pregnancy by quantitative serum hCG measurement on the day of each CCI admission.
- Women currently breastfeeding will also be excluded from the study.
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 |
|---|---|---|
| PlaceboPlacebo prepared by Investigation Drug Services at Brigham and Women's Hospital | Drug | Placebo |
| FludrocortisoneAlso: FlorinefFludrocortisone 0.1 mg | Drug | Fludrocortisone |
| EplerenoneAlso: InspraEpleronone 100 mg | Drug | Epleronone |
Primary outcome
Serum aldosterone after angiotensin II infusion
Time frame: 5 days
Aldosterone levels after 30 mins AngII infusion
3 secondary outcomes
Serum aldosterone after cosyntropin infusion
Time frame: 5 days
Serum cortisol after angiotensin II infusion
Time frame: 5 days
Serum cortisol after cosyntropin infusion
Time frame: 5 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2021.
- Background: PubMed 200147Braley LM, Williams GH. Rat adrenal cell sensitivity to angiotensin II, alpha-1-24-ACTH, and potassium: a comparative study. Am J Physiol. 1977 Nov;233(5):E402-6. doi: 10.1152/ajpendo.1977.233.5.E402.
- Derived from this study: PubMed 42581762Yuan YE, Adler GK, Rosner B, Merino AA, Guzelce EC, Williams GH, Williams JS, Haas AV. Investigating a Mineralocorticoid Receptor Mediation of an Ultra-Short Feedback Loop Regulating Aldosterone Production in Humans. Clin Endocrinol (Oxf). 2026 Aug 12. doi: 10.1111/cen.70189. Online ahead of print.
- Individual participant dataSharing planned: No
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Screening Protocol
Pain
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.
Jonathan S Williams, MD, MMSc principal investigator
Brigham and Women's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Fludrocortisone and Eplerenone in people with Healthy Volunteers, 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 3 inclusion and 5 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 8 Jun 2021. 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 phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Serum aldosterone after angiotensin II infusion (time frame: 5 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02871648, which also lists 2 linked publications.
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 8 Jun 2021.