HypertensionEarly Phase 1NCT01763541
Study of the Effect of Testosterone and Estradiol on NP Responses to Acute and Chronic Salt Loading
A Early Phase 1 study testing leuprolide acetate and Anastrozole in people with Hypertension, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
There is gender dimorphism in cardiovascular risk, with men at higher risk than women. However, the fundamental basis for the protective effect of female sex remains unclear. Recent data implicate the natriuretic peptide (NP) system as an important determinant of blood pressure. Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypertension
- What is being tested?
- leuprolide acetate and Anastrozole
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2014to Feb 2016
- Phase
- Early 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
- 18-40 years old
- no history of hypertension
- normal BMI
- Male: normal testosterone and free testosterone levels
- Female: regular menses, negative pregnancy test, no sex steroid therapy >/=3 mos
Who cannot join
- on hypertensives, diuretics, or insulin
- with diabetes mellitus
- estimated creatinine clearance <60 ml/min
- prior cardiovascular, liver or renal disease
- history of hormonally-responsive cancer
- elevated liver function test (LFTs)
Show all 15Show fewer
- atrial fibrillation
- abnormal sodium or potassium levels
- taking medications that directly impact the endocrine system (exogenous hormones, steroids, etc.)
- taking medications that indirectly impact the endocrine system (SSRIs, opioids, finasteride, etc.)
- with untreated hyper- or hypothyroidism
- smoker
- psychiatric history
- Women: not willing to abstain from getting pregnant during the course of the study, with abnormal menstrual cycle, or who have osteoporosis
- Men: with polycythemia
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Official title: Gonadal Steroid Regulation of the Natriuretic Peptide System
There is gender dimorphism in cardiovascular risk, with men at higher risk than women. However, the fundamental basis for the protective effect of female sex remains unclear. Recent data implicate the natriuretic peptide (NP) system as an important determinant of blood pressure. Also, NP levels are twice as high in women of reproductive age than in men, and gonadal steroids are important determinants of circulating NPs. These are the marked, but poorly understood differences in the NP status between men and women. The investigators hypothesize that gonadal steroids regulate NP release, specifically that testosterone inhibits and estrogen activates the NP axis, leading to differences in both resting NP levels and dynamic responses of the NP, RAAS, and kidneys to acute and chronic salt loading. Understanding the basis for gender differences in NP function should provide important insights regarding mechanisms underlying hypertension in men versus women.
- Conditions
- Hypertension
- Being tested
- leuprolide acetate, Anastrozole
- Keywords
- Natriuretic Peptides
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
leuprolide acetateDrug
Also called Lupron Depot 3.75 mg and 7.5 mg
Given to both arms to induce hypogonadism
AnastrozoleDrug
Also called Arimidex
Given to men to prevent conversion of administered testosterone to estradiol.
| Study group | Role | What they receive |
|---|---|---|
| Testosterone | Other | To determine the effect of testosterone on the NP responses to acute and chronic salt loading.
One testosterone patch (Androderm 5 mg) applied to each male subject each day for 14 days.
Intervention: Leuprolide acetate and anastrozole Receives: Drug: leuprolide acetate; Drug: Anastrozole |
| Estradiol | Other | To determine the effect of estradiol on the NP responses to acute and chronic salt loading.
Two estradiol patches (Vivelle Dot 0.1mg) will be applied to each female subject twice-a-week for 2 weeks.
Intervention: leuprolide acetate Receives: Drug: leuprolide acetate |
What is being measured
The primary outcome is the main question the study is designed to answer.
NP levels in men with testosterone patch and low-salt diet
B-type natriuretic peptide (BNP), Atrial natriuretic peptide (ANP), amino-terminal brain natiuretic peptide (N-BNP), amino-terminal atrial natiuretic peptide (N-ANP), cyclic guanosine monophosphate (cGMP)
Measured: At day 7 of week of testosterone administration with low-salt diet
NP levels in men with testosterone patch and high-salt diet
B-type natriuretic peptide (BNP), Atrial natriuretic peptide (ANP), amino-terminal brain natiuretic peptide (N-BNP), amino-terminal atrial natiuretic peptide (N-ANP), cyclic guanosine monophosphate (cGMP)
Measured: At day 7 of week of testosterone administration with high-salt diet
NP levels in women with estradiol patch and low-salt diet
B-type natriuretic peptide (BNP), Atrial natriuretic peptide (ANP), amino-terminal brain natiuretic peptide (N-BNP), amino-terminal atrial natiuretic peptide (N-ANP), cyclic guanosine monophosphate (cGMP)
Measured: At day 7 of week of estradiol administration with low-salt diet
NP levels in women with estradiol patch and high-salt diet
B-type natriuretic peptide (BNP), Atrial natriuretic peptide (ANP), amino-terminal brain natiuretic peptide (N-BNP), amino-terminal atrial natiuretic peptide (N-ANP), cyclic guanosine monophosphate (cGMP)
Measured: At day 7 of week of estradiol administration with high-salt diet
NP levels in men with placebo patch and low-salt diet
B-type natriuretic peptide (BNP), Atrial natriuretic peptide (ANP), amino-terminal brain natiuretic peptide (N-BNP), amino-terminal atrial natiuretic peptide (N-ANP), cyclic guanosine monophosphate (cGMP)
Measured: At day 7 of week of placebo administration with low-salt diet
NP levels in men with placebo patch and high-salt diet
B-type natriuretic peptide (BNP), Atrial natriuretic peptide (ANP), amino-terminal brain natiuretic peptide (N-BNP), amino-terminal atrial natiuretic peptide (N-ANP), cyclic guanosine monophosphate (cGMP)
Measured: At day 7 of week of placebo administration with high-salt diet
NP levels in women with placebo patch and low-salt diet
B-type natriuretic peptide (BNP), Atrial natriuretic peptide (ANP), amino-terminal brain natiuretic peptide (N-BNP), amino-terminal atrial natiuretic peptide (N-ANP), cyclic guanosine monophosphate (cGMP)
Measured: At day 7 of week of placebo administration with low-salt diet
NP levels in women with placebo patch and high-salt diet
B-type natriuretic peptide (BNP), Atrial natriuretic peptide (ANP), amino-terminal brain natiuretic peptide (N-BNP), amino-terminal atrial natiuretic peptide (N-ANP), cyclic guanosine monophosphate (cGMP)
Measured: At day 7 of week of placebo administration with high-salt diet
Secondary outcomes (20)
Plasma Renin Activity (PRA) levels in women on estradiol on low-salt diet
Plasma Renin Activity (PRA)
Measured: At day 7 of week of estradiol administration on low-salt diet
Aldosterone levels in men with testosterone on low-salt diet
Aldosterone
Measured: At day 7 of week of testosterone administration on low-salt diet
Plasma Renin Activity (PRA) levels in women on estradiol on high-salt diet
Plasma Renin Activity (PRA)
Measured: At days 6 and 7 of week of estradiol administration on high-salt diet
Plasma Renin Activity (PRA) levels in women on placebo on low-salt diet
Plasma Renin Activity (PRA)
Measured: At day 7 of week of placebo administration on low-salt diet
Plasma Renin Activity (PRA) levels in women on placebo on high-salt diet
Plasma Renin Activity (PRA)
Measured: At days 6 and 7 of week of placebo administration on high-salt diet
Plasma Renin Activity (PRA) levels in men on testosterone on low-salt diet
Measured: At day 7 of week of testosterone administration on low-salt diet
Plasma Renin Activity (PRA) levels in men on testosterone on high-salt diet
Measured: At days 6 and 7 of week of testosterone administration on high-salt diet
Plasma Renin Activity (PRA) levels in men on placebo on low-salt diet
Measured: At day 7 of week of placebo administration on low-salt diet
Plasma Renin Activity (PRA) levels in men on placebo on high-salt diet
Measured: At days 6 and 7 of week of placebo administration on high-salt diet
Aldosterone levels in men on testosterone on high-salt diet
Measured: At days 6 and 7 of week of testosterone administration on high-salt diet
Aldosterone levels in men on placebo on high-salt diet
Measured: At days 6 and 7 of week of placebo administration on high-salt diet
Aldosterone levels in men on placebo on low-salt diet
Measured: At day 7 of week of placebo administration on low-salt diet
Aldosterone levels in women on estradiol on high-salt diet
Measured: At days 6 and 7 of week of estradiol administration on high-salt diet
Aldosterone levels in women on estradiol on low-salt diet
Measured: At day 7 of week of estradiol administration on low-salt diet
Aldosterone levels in women on placebo on high-salt diet
Measured: At days 6 and 7 of week of placebo administration on high-salt diet
Aldosterone levels in women on placebo on low-salt diet
Measured: At day 7 of week of placebo administration on low-salt diet
Urinary sodium concentration in women on estradiol on high-salt diet
Measured: 0, 60, and 120 minute of saline infusion on morning of day 7 of estradiol administration on high-salt diet
Urinary sodium concentration in women on placebo on high-salt diet
Measured: 0, 60, and 120 minute of saline infusion on morning of day 7 of placebo administration on high-salt diet
Urinary sodium concentration in men on testosterone on high-salt diet
Measured: 0, 60, and 120 minute of saline infusion on morning of day 7 of testosterone administration on high-salt diet
Urinary sodium concentration in men on placebo on high-salt diet
Measured: 0, 60, and 120 minute of saline infusion on morning of day 7 of placebo administration on high-salt diet
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2013 (estimated)
- Study startJun 2014
- Primary completionFeb 2016
- Study completionFeb 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HypertensionStudies of the same condition, open and under way.
- More trials run by Massachusetts General 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
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Karen Klahr Miller, MD, Massachusetts General Hospital
- Investigators
- Karen Miller, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01763541
- Sponsor's protocol ID
- 2012P002337
- Status last verified
- Oct 2017
- First submitted
- 13 Nov 2012
- Last updated
- 19 Oct 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Gonadal Steroid Regulation of the Natriuretic Peptide System
- ClinicalTrials.gov ID
- NCT01763541
- Acronym / sponsor ID
- 2012P002337
- Conditions
- Hypertension
- Keywords
- Natriuretic Peptides
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- Jun 2014
- Primary completion
- Feb 2016 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 9 Jan 2013 (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.
There is gender dimorphism in cardiovascular risk, with men at higher risk than women. However, the fundamental basis for the protective effect of female sex remains unclear. Recent data implicate the natriuretic peptide (NP) system as an important determinant of blood pressure. Also, NP levels are twice as high in women of reproductive age than in men, and gonadal steroids are important determinants of circulating NPs. These are the marked, but poorly understood differences in the NP status between men and women. The investigators hypothesize that gonadal steroids regulate NP release, specifically that testosterone inhibits and estrogen activates the NP axis, leading to differences in both resting NP levels and dynamic responses of the NP, RAAS, and kidneys to acute and chronic salt loading. Understanding the basis for gender differences in NP function should provide important insights regarding mechanisms underlying hypertension in men versus women.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Testosterone | Other | Drug: leuprolide acetate, Drug: AnastrozoleTo determine the effect of testosterone on the NP responses to acute and chronic salt loading. One testosterone patch (Androderm 5 mg) applied to each male subject each day for 14 days. Intervention: Leuprolide acetate and anastrozole |
| Estradiol | Other | Drug: leuprolide acetateTo determine the effect of estradiol on the NP responses to acute and chronic salt loading. Two estradiol patches (Vivelle Dot 0.1mg) will be applied to each female subject twice-a-week for 2 weeks. Intervention: leuprolide acetate |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 18-40 years old
- no history of hypertension
- normal BMI
- Male: normal testosterone and free testosterone levels
- Female: regular menses, negative pregnancy test, no sex steroid therapy >/=3 mos
Key exclusion criteria (15 listed)
- on hypertensives, diuretics, or insulin
- with diabetes mellitus
- estimated creatinine clearance <60 ml/min
- prior cardiovascular, liver or renal disease
- history of hormonally-responsive cancer
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 |
|---|---|---|
| leuprolide acetateAlso: Lupron Depot 3.75 mg and 7.5 mgGiven to both arms to induce hypogonadism | Drug | Estradiol, Testosterone |
| AnastrozoleAlso: ArimidexGiven to men to prevent conversion of administered testosterone to estradiol. | Drug | Testosterone |
Primary outcome
NP levels in men with testosterone patch and low-salt diet
Time frame: At day 7 of week of testosterone administration with low-salt diet
B-type natriuretic peptide (BNP), Atrial natriuretic peptide (ANP), amino-terminal brain natiuretic peptide (N-BNP), amino-terminal atrial natiuretic peptide (N-ANP), cyclic guanosine monophosphate (cGMP)
NP levels in men with testosterone patch and high-salt diet
Time frame: At day 7 of week of testosterone administration with high-salt diet
B-type natriuretic peptide (BNP), Atrial natriuretic peptide (ANP), amino-terminal brain natiuretic peptide (N-BNP), amino-terminal atrial natiuretic peptide (N-ANP), cyclic guanosine monophosphate (cGMP)
NP levels in women with estradiol patch and low-salt diet
Time frame: At day 7 of week of estradiol administration with low-salt diet
B-type natriuretic peptide (BNP), Atrial natriuretic peptide (ANP), amino-terminal brain natiuretic peptide (N-BNP), amino-terminal atrial natiuretic peptide (N-ANP), cyclic guanosine monophosphate (cGMP)
NP levels in women with estradiol patch and high-salt diet
Time frame: At day 7 of week of estradiol administration with high-salt diet
B-type natriuretic peptide (BNP), Atrial natriuretic peptide (ANP), amino-terminal brain natiuretic peptide (N-BNP), amino-terminal atrial natiuretic peptide (N-ANP), cyclic guanosine monophosphate (cGMP)
NP levels in men with placebo patch and low-salt diet
Time frame: At day 7 of week of placebo administration with low-salt diet
B-type natriuretic peptide (BNP), Atrial natriuretic peptide (ANP), amino-terminal brain natiuretic peptide (N-BNP), amino-terminal atrial natiuretic peptide (N-ANP), cyclic guanosine monophosphate (cGMP)
NP levels in men with placebo patch and high-salt diet
Time frame: At day 7 of week of placebo administration with high-salt diet
B-type natriuretic peptide (BNP), Atrial natriuretic peptide (ANP), amino-terminal brain natiuretic peptide (N-BNP), amino-terminal atrial natiuretic peptide (N-ANP), cyclic guanosine monophosphate (cGMP)
NP levels in women with placebo patch and low-salt diet
Time frame: At day 7 of week of placebo administration with low-salt diet
B-type natriuretic peptide (BNP), Atrial natriuretic peptide (ANP), amino-terminal brain natiuretic peptide (N-BNP), amino-terminal atrial natiuretic peptide (N-ANP), cyclic guanosine monophosphate (cGMP)
NP levels in women with placebo patch and high-salt diet
Time frame: At day 7 of week of placebo administration with high-salt diet
B-type natriuretic peptide (BNP), Atrial natriuretic peptide (ANP), amino-terminal brain natiuretic peptide (N-BNP), amino-terminal atrial natiuretic peptide (N-ANP), cyclic guanosine monophosphate (cGMP)
20 secondary outcomes
Plasma Renin Activity (PRA) levels in women on estradiol on low-salt diet
Time frame: At day 7 of week of estradiol administration on low-salt diet
Aldosterone levels in men with testosterone on low-salt diet
Time frame: At day 7 of week of testosterone administration on low-salt diet
Plasma Renin Activity (PRA) levels in women on estradiol on high-salt diet
Time frame: At days 6 and 7 of week of estradiol administration on high-salt diet
Plasma Renin Activity (PRA) levels in women on placebo on low-salt diet
Time frame: At day 7 of week of placebo administration on low-salt diet
Plasma Renin Activity (PRA) levels in women on placebo on high-salt diet
Time frame: At days 6 and 7 of week of placebo administration on high-salt diet
Plasma Renin Activity (PRA) levels in men on testosterone on low-salt diet
Time frame: At day 7 of week of testosterone administration on low-salt diet
Plasma Renin Activity (PRA) levels in men on testosterone on high-salt diet
Time frame: At days 6 and 7 of week of testosterone administration on high-salt diet
Plasma Renin Activity (PRA) levels in men on placebo on low-salt diet
Time frame: At day 7 of week of placebo administration on low-salt diet
Plasma Renin Activity (PRA) levels in men on placebo on high-salt diet
Time frame: At days 6 and 7 of week of placebo administration on high-salt diet
Aldosterone levels in men on testosterone on high-salt diet
Time frame: At days 6 and 7 of week of testosterone administration on high-salt diet
Aldosterone levels in men on placebo on high-salt diet
Time frame: At days 6 and 7 of week of placebo administration on high-salt diet
Aldosterone levels in men on placebo on low-salt diet
Time frame: At day 7 of week of placebo administration on low-salt diet
Aldosterone levels in women on estradiol on high-salt diet
Time frame: At days 6 and 7 of week of estradiol administration on high-salt diet
Aldosterone levels in women on estradiol on low-salt diet
Time frame: At day 7 of week of estradiol administration on low-salt diet
Aldosterone levels in women on placebo on high-salt diet
Time frame: At days 6 and 7 of week of placebo administration on high-salt diet
Aldosterone levels in women on placebo on low-salt diet
Time frame: At day 7 of week of placebo administration on low-salt diet
Urinary sodium concentration in women on estradiol on high-salt diet
Time frame: 0, 60, and 120 minute of saline infusion on morning of day 7 of estradiol administration on high-salt diet
Urinary sodium concentration in women on placebo on high-salt diet
Time frame: 0, 60, and 120 minute of saline infusion on morning of day 7 of placebo administration on high-salt diet
Urinary sodium concentration in men on testosterone on high-salt diet
Time frame: 0, 60, and 120 minute of saline infusion on morning of day 7 of testosterone administration on high-salt diet
Urinary sodium concentration in men on placebo on high-salt diet
Time frame: 0, 60, and 120 minute of saline infusion on morning of day 7 of placebo administration on high-salt diet
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2017.
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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.
Karen Miller, MD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing leuprolide acetate and Anastrozole in people with Hypertension, run by Massachusetts General 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 5 inclusion and 15 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: withdrawn, as of the sponsor's last update on 19 Oct 2017. 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. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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 was withdrawn before enrolling participants, so there are no results.
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?
NP levels in men with testosterone patch and low-salt diet (time frame: At day 7 of week of testosterone administration with low-salt diet). The study lists 8 primary outcomes in all. 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 19 Oct 2017; AzTrials last refreshed its copy on 7 Nov 2026.