Clinical trial NCT01763541: 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
Overall status: WITHDRAWN
Phase: EARLY_PHASE1
Conditions: Hypertension
Keywords: Natriuretic Peptides
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2013-01-09
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


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

Primary outcomes:
measure: NP levels in men with testosterone patch and low-salt diet
timeFrame: At day 7 of week of testosterone administration with low-salt diet
measure: NP levels in men with testosterone patch and high-salt diet
timeFrame: At day 7 of week of testosterone administration with high-salt diet
measure: NP levels in women with estradiol patch and low-salt diet
timeFrame: At day 7 of week of estradiol administration with low-salt diet
measure: NP levels in women with estradiol patch and high-salt diet
timeFrame: At day 7 of week of estradiol administration with high-salt diet
measure: NP levels in men with placebo patch and low-salt diet
timeFrame: At day 7 of week of placebo administration with low-salt diet
measure: NP levels in men with placebo patch and high-salt diet
timeFrame: At day 7 of week of placebo administration with high-salt diet
measure: NP levels in women with placebo patch and low-salt diet
timeFrame: At day 7 of week of placebo administration with low-salt diet
measure: NP levels in women with placebo patch and high-salt diet
timeFrame: At day 7 of week of placebo administration with high-salt diet
Secondary outcomes:
measure: Plasma Renin Activity (PRA) levels in women on estradiol on low-salt diet
timeFrame: At day 7 of week of estradiol administration on low-salt diet
measure: Aldosterone levels in men with testosterone on low-salt diet
timeFrame: At day 7 of week of testosterone administration on low-salt diet
measure: Plasma Renin Activity (PRA) levels in women on estradiol on high-salt diet
timeFrame: At days 6 and 7 of week of estradiol administration on high-salt diet
measure: Plasma Renin Activity (PRA) levels in women on placebo on low-salt diet
timeFrame: At day 7 of week of placebo administration on low-salt diet
measure: Plasma Renin Activity (PRA) levels in women on placebo on high-salt diet
timeFrame: At days 6 and 7 of week of placebo administration on high-salt diet
measure: Plasma Renin Activity (PRA) levels in men on testosterone on low-salt diet
timeFrame: At day 7 of week of testosterone administration on low-salt diet
measure: Plasma Renin Activity (PRA) levels in men on testosterone on high-salt diet
timeFrame: At days 6 and 7 of week of testosterone administration on high-salt diet
measure: Plasma Renin Activity (PRA) levels in men on placebo on low-salt diet
timeFrame: At day 7 of week of placebo administration on low-salt diet
measure: Plasma Renin Activity (PRA) levels in men on placebo on high-salt diet
timeFrame: At days 6 and 7 of week of placebo administration on high-salt diet
measure: Aldosterone levels in men on testosterone on high-salt diet
timeFrame: At days 6 and 7 of week of testosterone administration on high-salt diet
measure: Aldosterone levels in men on placebo on high-salt diet
timeFrame: At days 6 and 7 of week of placebo administration on high-salt diet
measure: Aldosterone levels in men on placebo on low-salt diet
timeFrame: At day 7 of week of placebo administration on low-salt diet
measure: Aldosterone levels in women on estradiol on high-salt diet
timeFrame: At days 6 and 7 of week of estradiol administration on high-salt diet
measure: Aldosterone levels in women on estradiol on low-salt diet
timeFrame: At day 7 of week of estradiol administration on low-salt diet
measure: Aldosterone levels in women on placebo on high-salt diet
timeFrame: At days 6 and 7 of week of placebo administration on high-salt diet
measure: Aldosterone levels in women on placebo on low-salt diet
timeFrame: At day 7 of week of placebo administration on low-salt diet
measure: Urinary sodium concentration in women on estradiol on high-salt diet
timeFrame: 0, 60, and 120 minute of saline infusion on morning of day 7 of estradiol administration on high-salt diet
measure: Urinary sodium concentration in women on placebo on high-salt diet
timeFrame: 0, 60, and 120 minute of saline infusion on morning of day 7 of placebo administration on high-salt diet
measure: Urinary sodium concentration in men on testosterone on high-salt diet
timeFrame: 0, 60, and 120 minute of saline infusion on morning of day 7 of testosterone administration on high-salt diet
measure: Urinary sodium concentration in men on placebo on high-salt diet
timeFrame: 0, 60, and 120 minute of saline infusion on morning of day 7 of placebo administration on high-salt diet
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Karen Miller, MD
role: PRINCIPAL_INVESTIGATOR
References: