Study of the Effect of Testosterone and Estradiol on NP Responses to Acute and Chronic Salt Loading

October 17, 2017 updated by: Karen Klahr Miller, MD, Massachusetts General Hospital

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 36 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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)
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: Testosterone

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
Drug: leuprolide acetate
Given to both arms to induce hypogonadism
Other Names:
  • Lupron Depot 3.75 mg and 7.5 mg
Drug: Anastrozole
Given to men to prevent conversion of administered testosterone to estradiol.
Other Names:
  • Arimidex
Other: Estradiol

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
Drug: leuprolide acetate
Given to both arms to induce hypogonadism
Other Names:
  • Lupron Depot 3.75 mg and 7.5 mg

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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)
At day 7 of week of testosterone administration with low-salt diet
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)
At day 7 of week of testosterone administration with high-salt diet
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)
At day 7 of week of estradiol administration with low-salt diet
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)
At day 7 of week of estradiol administration with high-salt diet
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)
At day 7 of week of placebo administration with low-salt diet
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)
At day 7 of week of placebo administration with high-salt diet
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)
At day 7 of week of placebo administration with low-salt diet
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)
At day 7 of week of placebo administration with high-salt diet

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
Plasma Renin Activity (PRA)
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
Aldosterone
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)
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)
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)
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
0, 60, and 120 minute of saline infusion on morning of day 7 of placebo administration on high-salt diet

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Massachusetts General Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Karen Miller, MD, Massachusetts General Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 13, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 4, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 9, 2013

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 19, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 17, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2012P002337

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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