Treatment of Adiposity Related hypErTension (TARGET)
Condition: Hypertension; Abdominal Obesity; Metabolic Syndrome
MeSH terms: Hypertension; Obesity; Metabolic Syndrome; Obesity, Abdominal
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Aliskiren; Moxonidine; Hydrochlorothiazide; Placebo (for aliskiren); Placebo (for moxonidine and hydrochlorothiazide)
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): Once daily treatment with aliskiren for 8-weeks, according to the following regiment: once daily (morning time) 150 mg during the first 2 weeks, followed by once daily (morning time) 300 mg during the remaining 6 weeks. Coincidental intake of grapefruit(juice) should be avoided. This treatment interval is followed by a one-week tapering period: 150 mg on day 1, 2, 3, 4, 5 and 7.; Once daily treatment with moxonidine for 8-weeks, according to the following regiment: once daily (morning time) 0.2 mg during the first 2 weeks, followed by once daily (morning time) 0.4 mg during the remaining 6 weeks. Coincidental intake of grapefruit(juice) should be avoided. This treatment interval is followed by a one-week tapering period: 0.2 mg on day 1, 2, 3, 4, 5 and 7.; Once daily treatment with hydrochlorothiazide for 8-weeks, according to the following regiment: once daily (morning time) 12.5 mg during the first 2 weeks, followed by once daily (morning time) 25 mg during the remaining 6 weeks. Coincidental intake of grapefruit(juice) should be avoided. This treatment interval is followed by a one-week tapering period: 12.5 mg on day 1, 2, 3, 4, 5 and 7.; Once daily treatment with placebo tablets for 8-weeks, according to the following regiment: once daily (morning time) 1 tablet during the first 2 weeks, followed by once daily (morning time) 2 tablets during the remaining 6 weeks. Coincidental intake of grapefruit(juice) should be avoided. This treatment interval is followed by a one-week tapering period: 1 tablet on day 1, 2, 3, 4, 5 and 7.; Once daily treatment with placebo capsules for 8-weeks, according to the following regiment: once daily (morning time) 1 capsule during the first 2 weeks, followed by once daily (morning time) 2 capsules during the remaining 6 weeks. Coincidental intake of grapefruit(juice) should be avoided. This treatment interval is followed by a one-week tapering period: 1 tablet on day 1, 2, 3, 4, 5 and 7.
Other intervention name(s): Brand name: Ralisez; ATC-code: C09XA02; No brand name (generic product); ATC-code: C02AC05; No brand name (generic product); ATC-code: C03AA03
Intervention MeSH terms: Hydrochlorothiazide; Moxonidine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Hypertension; Metabolic Syndrome X; Obesity; Adiposity; Clinical trial