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

Hypertension Clinical Trial

Official title:

Gonadal Steroid Regulation of the Natriuretic Peptide System

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01763541
• Other study ID #: 2012P002337
• Status: Withdrawn
• Phase: Early Phase 1
• First received: November 13, 2012
• Last updated: October 17, 2017
• Start date: June 2014
• Est. completion date: February 2016

Study information

• Verified date: October 2017
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: February 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypertension

Intervention

Drug:
• leuprolide acetate
Given to both arms to induce hypogonadism
• Anastrozole
Given to men to prevent conversion of administered testosterone to estradiol.

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	At day 7 of week of testosterone administration with low-salt diet
Primary	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)	At day 7 of week of testosterone administration with high-salt diet
Primary	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)	At day 7 of week of estradiol administration with low-salt diet
Primary	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)	At day 7 of week of estradiol administration with high-salt diet
Primary	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)	At day 7 of week of placebo administration with low-salt diet
Primary	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)	At day 7 of week of placebo administration with high-salt diet
Primary	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)	At day 7 of week of placebo administration with low-salt diet
Primary	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)	At day 7 of week of placebo administration with high-salt diet
Secondary	Plasma Renin Activity (PRA) levels in women on estradiol on low-salt diet	Plasma Renin Activity (PRA)	At day 7 of week of estradiol administration on low-salt diet
Secondary	Aldosterone levels in men with testosterone on low-salt diet	Aldosterone	At day 7 of week of testosterone administration on low-salt diet
Secondary	Plasma Renin Activity (PRA) levels in women on estradiol on high-salt diet	Plasma Renin Activity (PRA)	At days 6 and 7 of week of estradiol administration on high-salt diet
Secondary	Plasma Renin Activity (PRA) levels in women on placebo on low-salt diet	Plasma Renin Activity (PRA)	At day 7 of week of placebo administration on low-salt diet
Secondary	Plasma Renin Activity (PRA) levels in women on placebo on high-salt diet	Plasma Renin Activity (PRA)	At days 6 and 7 of week of placebo administration on high-salt diet
Secondary	Plasma Renin Activity (PRA) levels in men on testosterone on low-salt diet		At day 7 of week of testosterone administration on low-salt diet
Secondary	Plasma Renin Activity (PRA) levels in men on testosterone on high-salt diet		At days 6 and 7 of week of testosterone administration on high-salt diet
Secondary	Plasma Renin Activity (PRA) levels in men on placebo on low-salt diet		At day 7 of week of placebo administration on low-salt diet
Secondary	Plasma Renin Activity (PRA) levels in men on placebo on high-salt diet		At days 6 and 7 of week of placebo administration on high-salt diet
Secondary	Aldosterone levels in men on testosterone on high-salt diet		At days 6 and 7 of week of testosterone administration on high-salt diet
Secondary	Aldosterone levels in men on placebo on high-salt diet		At days 6 and 7 of week of placebo administration on high-salt diet
Secondary	Aldosterone levels in men on placebo on low-salt diet		At day 7 of week of placebo administration on low-salt diet
Secondary	Aldosterone levels in women on estradiol on high-salt diet		At days 6 and 7 of week of estradiol administration on high-salt diet
Secondary	Aldosterone levels in women on estradiol on low-salt diet		At day 7 of week of estradiol administration on low-salt diet
Secondary	Aldosterone levels in women on placebo on high-salt diet		At days 6 and 7 of week of placebo administration on high-salt diet
Secondary	Aldosterone levels in women on placebo on low-salt diet		At day 7 of week of placebo administration on low-salt diet
Secondary	Urinary sodium concentration in women on estradiol on high-salt diet		0, 60, and 120 minute of saline infusion on morning of day 7 of estradiol administration on high-salt diet
Secondary	Urinary sodium concentration in women on placebo on high-salt diet		0, 60, and 120 minute of saline infusion on morning of day 7 of placebo administration on high-salt diet
Secondary	Urinary sodium concentration in men on testosterone on high-salt diet		0, 60, and 120 minute of saline infusion on morning of day 7 of testosterone administration on high-salt diet
Secondary	Urinary sodium concentration in men on placebo on high-salt diet		0, 60, and 120 minute of saline infusion on morning of day 7 of placebo administration on high-salt diet