Treatment of Adiposity Related hypErTension (TARGET)

Phase 4

Completed

• Conditions: Hypertension; Abdominal Obesity; Metabolic Syndrome
• Interventions: Drug: Hydrochlorothiazide; Drug: Aliskiren; Drug: Moxonidine; Drug: Placebo (for moxonidine and hydrochlorothiazide); Drug: Placebo (for aliskiren)

• Registration Number: NCT01138423
• Lead Sponsor: UMC Utrecht

Brief Summary

High blood pressure (hypertension) is an important cause of myocardial infarction and stroke. High blood pressure often occurs in people who are overweight. These people frequently also have abnormal fat and sugar metabolism. The combination of these problems is called the 'metabolic syndrome'.

People with hypertension and obesity currently receive the same drug therapy as people with hypertension, but without obesity. Different classes of drugs are thought to be equally effective in lowering blood pressure.

Next to lowering blood pressure, hypertension treatment can have additional effects, like changes in blood vessel function (the ability to dilate and constrict) or changes is the metabolism of sugar and fat. Particularly in patients with the metabolic syndrome, these additional effects are thought to be of great importance, because they can influence the risk for cardiovascular diseases.

The blood pressure lowering mechanism differs between classes of blood pressure lowering medication. The purpose of this study is to compare the effects of three types of blood pressure lowering medication belonging to different classes. The main outcomes of interest will be blood vessel function (the ability to dilate and constrict) and blood pressure. Moreover, the effect of treatment on additional outcomes, like metabolism of sugar and fat, will be studied.

Detailed Description

Treatment of obesity related hypertension (ORH) is challenging and has become an important global health problem. According to guidelines, most classes of antihypertensives are equally effective for the treatment of hypertension. However, these guidelines are based on evidence from studies in patients with essential hypertension, but without a specific focus on ORH. There is an increasing body of evidence about the complex pathophysiological mechanisms of ORH. Adipose tissue dysfunction is commonly regarded as a common soil that eventually causes up regulation of the sympathetic nervous system (SNS) and the renin-angiotensin-system (RAS). Moreover, development of hypertension is closely related to development of endothelial dysfunction, dyslipidemia and disorders of glucose metabolism. The investigators hypothesize that treatment with antihypertensives that are directed at down regulation of the SNS (moxonidine) and the RAS (aliskiren) will result in more beneficial effects than treatment with a diuretic (hydrochlorothiazide), because the latter reduces blood pressure by inhibition of sodium resorption, without influencing the underlying disease mechanism. The main outcomes of interest are endothelial function and blood pressure, but many secondary outcomes are studied too.

Study Timeline

• Study First Submitted: 2010-06-04
• Study First Submitted QC: 2010-06-04
• Study First Posted: 2010-06-07
• Study Start: 2010-08
• Status Verified: 2012-02
• Primary Completion: 2012-02
• Study Completion: 2012-02
• Last Update Submitted: 2012-02-23
• Last Update Posted: 2012-02-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Aliskiren	Placebo (for moxonidine and hydrochlorothiazide)	-
Moxonidine	Placebo (for aliskiren)	-
Hydrochlorothiazide	Hydrochlorothiazide	-
Hydrochlorothiazide	Placebo (for aliskiren)	-
Placebo	Placebo (for aliskiren)	-
Placebo	Placebo (for moxonidine and hydrochlorothiazide)	-
Aliskiren	Aliskiren	-
Moxonidine	Moxonidine	-

Primary Outcome Measures

Name	Time	Method
Endothelial function assessed by Flow Mediated Dilation (FMD)	After 8 weeks treatment

Secondary Outcome Measures

Name	Time	Method
Adipose tissue function (serum concentrations of adipokines)	After 8 weeks treatment
Lipid metabolism (serum lipid concentrations)	After 8 weeks treatment
Mean 24-hour systolic/diastolic blood pressure Mean day- and night time systolic/diastolic blood pressure	After 8 weeks treatment
Central Blood pressure (estimated with pulse wave analysis)	After 8 weeks treatment
Renin-Angiotensin System (RAS) hormone concentrations	After 8 weeks treatment
Sympathetic nervous system activity, assessed by Muscle Sympathetic Nerve Activity (MSNA) and Heart Rate Variability (HRV)	After 8 weeks treatment
Markers of oxidative stress (concentrations of F2-isoprostanes in urine and oxLDL in plasma)	After 8 weeks treatment
Markers of inflammation (hs-CRP in plasma)	After 8 weeks treatment
Fractional sodium excretion	After 8 weeks treatment
Arterial stiffness (assessed by pulse wave velocity and the pulse wave analysis augmentation index)	After 8 weeks treatment
Insulin sensitivity, expressed by homeostatic model assessment (HOMA)	After 8 weeks treatment

Trial Locations

Locations (1)

UMC Utrecht; 🇳🇱 Utrecht, Netherlands