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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified February 2014 by Massachusetts General Hospital
Sponsor:
Information provided by (Responsible Party):
Karen Klahr Miller, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01763541
First received: November 13, 2012
Last updated: February 20, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Hypertension
Drug: leuprolide acetate
Drug: Anastrozole
Phase 0

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: Gonadal Steroid Regulation of the Natriuretic Peptide System

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: At day 7 of week of estradiol administration on low-salt diet ] [ Designated as safety issue: No ]
    Plasma Renin Activity (PRA)

  • Aldosterone levels in men with testosterone on low-salt diet [ Time Frame: At day 7 of week of testosterone administration on low-salt diet ] [ Designated as safety issue: No ]
    Aldosterone

  • 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 ] [ Designated as safety issue: No ]
    Plasma Renin Activity (PRA)

  • 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 ] [ Designated as safety issue: No ]
    Plasma Renin Activity (PRA)

  • 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 ] [ Designated as safety issue: No ]
    Plasma Renin Activity (PRA)

  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Aldosterone levels in men on placebo on low-salt diet [ Time Frame: At day 7 of week of placebo administration on low-salt diet ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Aldosterone levels in women on estradiol on low-salt diet [ Time Frame: At day 7 of week of estradiol administration on low-salt diet ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Aldosterone levels in women on placebo on low-salt diet [ Time Frame: At day 7 of week of placebo administration on low-salt diet ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 250
Study Start Date: June 2014
Estimated Study Completion Date: January 2018
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Lupron Depot 3.75 mg and 7.5 mg
Drug: Anastrozole
Given to men to prevent conversion of administered testosterone to estradiol.
Other Name: Arimidex
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 Name: Lupron Depot 3.75 mg and 7.5 mg

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01763541

Contacts
Contact: Anu V Gerweck, NP 617-724-1837 avgerweck@partners.org
Contact: Melissa G Landa, BA 617-724-0785 mlanda3@partners.org

Locations
United States, Massachusetts
Massachusetts General Hospital Not yet recruiting
Boston, Massachusetts, United States, 02114
Contact: Anu V Gerweck, NP    617-724-1837    avgerweck@partners.org   
Contact: Melissa G Landa, BA    617-724-0785    mlanda3@partners.org   
Principal Investigator: Karen Miller, MD         
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Karen Miller, MD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Karen Klahr Miller, MD, Director, Neuroendocrine Research Program in Women's Health, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01763541     History of Changes
Other Study ID Numbers: 2012P002337
Study First Received: November 13, 2012
Last Updated: February 20, 2014
Health Authority: United States: Data and Safety Monitoring Board
United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
Natriuretic Peptides

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases
Testosterone
Testosterone enanthate
Testosterone undecanoate
Testosterone 17 beta-cypionate
Methyltestosterone
Estradiol
Polyestradiol phosphate
Leuprolide
Anastrozole
Estradiol valerate
Estradiol 17 beta-cypionate
Estradiol 3-benzoate
Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Anabolic Agents
Estrogens
Contraceptive Agents
Reproductive Control Agents
Contraceptive Agents, Female
Fertility Agents, Female
Fertility Agents

ClinicalTrials.gov processed this record on September 22, 2014