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

Primary Purpose

Hypertension

Status
Withdrawn
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
leuprolide acetate
Anastrozole
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Hypertension focused on measuring Natriuretic Peptides

Eligibility Criteria

18 Years - 40 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Massachusetts General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

Testosterone

Estradiol

Arm Description

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

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

Outcomes

Primary Outcome Measures

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)
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)
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)
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)
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)
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)
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)
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)

Secondary Outcome Measures

Plasma Renin Activity (PRA) levels in women on estradiol on low-salt diet
Plasma Renin Activity (PRA)
Aldosterone levels in men with testosterone on low-salt diet
Aldosterone
Plasma Renin Activity (PRA) levels in women on estradiol on high-salt diet
Plasma Renin Activity (PRA)
Plasma Renin Activity (PRA) levels in women on placebo on low-salt diet
Plasma Renin Activity (PRA)
Plasma Renin Activity (PRA) levels in women on placebo on high-salt diet
Plasma Renin Activity (PRA)
Plasma Renin Activity (PRA) levels in men on testosterone on low-salt diet
Plasma Renin Activity (PRA) levels in men on testosterone on high-salt diet
Plasma Renin Activity (PRA) levels in men on placebo on low-salt diet
Plasma Renin Activity (PRA) levels in men on placebo on high-salt diet
Aldosterone levels in men on testosterone on high-salt diet
Aldosterone levels in men on placebo on high-salt diet
Aldosterone levels in men on placebo on low-salt diet
Aldosterone levels in women on estradiol on high-salt diet
Aldosterone levels in women on estradiol on low-salt diet
Aldosterone levels in women on placebo on high-salt diet
Aldosterone levels in women on placebo on low-salt diet
Urinary sodium concentration in women on estradiol on high-salt diet
Urinary sodium concentration in women on placebo on high-salt diet
Urinary sodium concentration in men on testosterone on high-salt diet
Urinary sodium concentration in men on placebo on high-salt diet

Full Information

First Posted
November 13, 2012
Last Updated
October 17, 2017
Sponsor
Massachusetts General Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT01763541
Brief Title
Study of the Effect of Testosterone and Estradiol on NP Responses to Acute and Chronic Salt Loading
Official Title
Gonadal Steroid Regulation of the Natriuretic Peptide System
Study Type
Interventional

2. Study Status

Record Verification Date
October 2017
Overall Recruitment Status
Withdrawn
Study Start Date
June 2014 (undefined)
Primary Completion Date
February 2016 (Actual)
Study Completion Date
February 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertension
Keywords
Natriuretic Peptides

7. Study Design

Primary Purpose
Basic Science
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Testosterone
Arm Type
Other
Arm Description
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
Arm Title
Estradiol
Arm Type
Other
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
leuprolide acetate
Other Intervention Name(s)
Lupron Depot 3.75 mg and 7.5 mg
Intervention Description
Given to both arms to induce hypogonadism
Intervention Type
Drug
Intervention Name(s)
Anastrozole
Other Intervention Name(s)
Arimidex
Intervention Description
Given to men to prevent conversion of administered testosterone to estradiol.
Primary Outcome Measure Information:
Title
NP levels in men with testosterone patch and low-salt diet
Description
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)
Time Frame
At day 7 of week of testosterone administration with low-salt diet
Title
NP levels in men with testosterone patch and high-salt diet
Description
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)
Time Frame
At day 7 of week of testosterone administration with high-salt diet
Title
NP levels in women with estradiol patch and low-salt diet
Description
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)
Time Frame
At day 7 of week of estradiol administration with low-salt diet
Title
NP levels in women with estradiol patch and high-salt diet
Description
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)
Time Frame
At day 7 of week of estradiol administration with high-salt diet
Title
NP levels in men with placebo patch and low-salt diet
Description
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)
Time Frame
At day 7 of week of placebo administration with low-salt diet
Title
NP levels in men with placebo patch and high-salt diet
Description
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)
Time Frame
At day 7 of week of placebo administration with high-salt diet
Title
NP levels in women with placebo patch and low-salt diet
Description
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)
Time Frame
At day 7 of week of placebo administration with low-salt diet
Title
NP levels in women with placebo patch and high-salt diet
Description
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)
Time Frame
At day 7 of week of placebo administration with high-salt diet
Secondary Outcome Measure Information:
Title
Plasma Renin Activity (PRA) levels in women on estradiol on low-salt diet
Description
Plasma Renin Activity (PRA)
Time Frame
At day 7 of week of estradiol administration on low-salt diet
Title
Aldosterone levels in men with testosterone on low-salt diet
Description
Aldosterone
Time Frame
At day 7 of week of testosterone administration on low-salt diet
Title
Plasma Renin Activity (PRA) levels in women on estradiol on high-salt diet
Description
Plasma Renin Activity (PRA)
Time Frame
At days 6 and 7 of week of estradiol administration on high-salt diet
Title
Plasma Renin Activity (PRA) levels in women on placebo on low-salt diet
Description
Plasma Renin Activity (PRA)
Time Frame
At day 7 of week of placebo administration on low-salt diet
Title
Plasma Renin Activity (PRA) levels in women on placebo on high-salt diet
Description
Plasma Renin Activity (PRA)
Time Frame
At days 6 and 7 of week of placebo administration on high-salt diet
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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
Title
Aldosterone levels in men on placebo on low-salt diet
Time Frame
At day 7 of week of placebo administration on low-salt diet
Title
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
Title
Aldosterone levels in women on estradiol on low-salt diet
Time Frame
At day 7 of week of estradiol administration on low-salt diet
Title
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
Title
Aldosterone levels in women on placebo on low-salt diet
Time Frame
At day 7 of week of placebo administration on low-salt diet
Title
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
Title
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
Title
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
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Karen Miller, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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