Aldosterone Antagonism and Microvascular Function
Effects of Aldosterone Antagonism on Insulin-mediated Microvascular Function in Subjects With the Metabolic Syndrome
The prevalence of obesity and obesity-related complications is currently taking epidemic proportions. These complications increase the risk of type 2 diabetes and cardiovascular disease, which are important causes of morbidity and mortality worldwide.
It is important to gain insight in the mechanisms underlying obesity-related complications, because this may lead to the development of directed therapeutic strategies.
Currently, there is significant evidence that the cause of both insulin resistance and hypertension must be sought at the level of the microcirculation.
Over activity of the renin-angiotensin-aldosterone system is a potential cause of microvascular dysfunction. Angiotensin II was indeed found to be implicated in the pathogenesis of obesity-associated hypertension and insulin resistance, possibly through interference with the vascular effects of insulin.
Increased aldosterone levels have also been associated with resistant hypertension and insulin resistance, which is illustrated in patients with primary aldosteronism. Furthermore, aldosterone is known to exert several detrimental effects on the vasculature, some of which are offset by mineralocorticoid receptor antagonists.
In obese individuals, plasma aldosterone concentrations are increased as well. We hypothesize that increased aldosterone levels in adipose persons induce microvascular dysfunction, which contributes to the development of insulin resistance and hypertension, and mineralocorticoid receptor antagonism results in improved insulin sensitivity and decreased blood pressure by counteracting the adverse effects of aldosterone on the microvasculature.
연구 개요
연구 유형
등록 (실제)
단계
- 4단계
연락처 및 위치
연구 장소
-
-
Limburg
-
Maastricht, Limburg, 네덜란드, 6229 ER
- Maastricht University
-
-
참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
- Age 40-65 years
- Caucasian
- Waist circumference > 102 cm (men)/> 88 cm (women)
- Triglycerides > 1.7 mmol/L
- High-normal blood pressure (office blood pressure: 130/85 - 139/89 mm Hg) or stage I hypertension (office blood pressure: 140/90 mm Hg - 159/99 mm Hg; 24h ABPM: 125/80 - 149/89 mm Hg)
Exclusion Criteria:
- Cardiovascular disease (stroke, coronary artery disease, peripheral vascular disease, congestive heart failure, cardiac shunts, cardiac surgery, pulmonary hypertension, cardiac arrhythmias, family history of cardiac arrhythmias or sudden cardiac death)
- Diabetes mellitus/impaired glucose metabolism (fasting glucose values > 5.6 mmol/L)
- Grade 2 or 3 hypertension (office blood pressure: > 160/100 mm Hg; ABPM > 150/90 mm Hg)
- Unstable or severe pulmonary disease
- Unstable or severe thyroid disorders
- Inflammatory diseases
- Alcohol use > 2 U/day (women)/> 3 U/day (men)
- Use of antihypertensive, lipid-lowering or glucose-lowering medications,
- Use of corticosteroids, medication known to inhibit or induce CYP3A4, lithium, and tricyclic antidepressants or antipsychotic medication, and regular use (weekly or several times a week) of NSAIDs
- Plasma potassium levels < 3.2 mmol/L or > 5 mmol/L
- eGFR < 60 mL/min
- Impairment of hepatic function
- Pregnancy or lactation
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 기초 과학
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 삼루타
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
활성 비교기: Eplerenone
Eplerenone 50 mg 1dd during four weeks
|
|
|
위약 비교기: Placebo
Eplerenone-matched placebo
|
Eplerenone-matched placebo
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Change in capillary recruitment (insulin-induced increase in microvascular blood volume in skeletal muscle) from baseline after 4 weeks of Eplerenone treatment or placebo
기간: Change from baseline after 4 weeks of treatment with either Eplerenone or placebo
|
The difference in microvascular blood volume in skeletal muscle of the forearm, which is assessed with contrast enhanced ultrasound, before and during a hyperinsulinemic, euglycemic clamp (performed to determine insulin sensitivity)
|
Change from baseline after 4 weeks of treatment with either Eplerenone or placebo
|
공동 작업자 및 조사자
수사관
- 수석 연구원: prof. C.D.A. Stehouwer, MD, PhD, Maastricht University Medical Center
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (실제)
연구 완료 (실제)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (추정)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .
에플레논에 대한 임상 시험
-
Darnitsa Pharmaceutical CompanyACDIMA Biocenter완전한
-
National Institute of Allergy and Infectious Diseases...종료됨
-
NovartisIntegrium; Great Lakes Drug Development, Inc.완전한
-
Vanderbilt University Medical CenterNational Center for Research Resources (NCRR)완전한
-
Pr. Nicolas GIRERD모병