A Study on Molecular Genetics of Drug Responsiveness in Essential Hypertension
Condition: Hypertension; Pharmacogenetics
MeSH terms: Hypertension; Essential Hypertension
Study type: Interventional
Phase: Phase 4

Summary: 
      Blood pressure variation and the risk of essential hypertension have an important genetic
      component. In most cases susceptibility to essential hypertension is likely determined by the
      action of more than one gene.

      The identification of genes causing susceptibility to hypertension is important, since it
      would give new tools for the diagnosis and enable better etiological classification and
      specific treatment of the disease.

      The innovation of this study is to use the response to antihypertensive therapy as an
      intermediate phenotype.

      In the study, each subject uses one of four antihypertensive drugs, each as a monotherapy in
      a rotational fashion, for 28 days in a randomized order. The antihypertensive drugs to be
      tested include a thiazide diuretic, a beta-adrenergic antagonist, an angiotensin-II receptor
      antagonist and a calcium channel blocker. The drugs that are selected for the study are
      "typical" representatives of their groups and long-acting, and the dosages are sufficient but
      well tolerable.
    

Detailed description: 
      Blood pressure variation and the risk of essential hypertension have an important genetic
      component. In most cases susceptibility to essential hypertension is likely determined by the
      action of more than one gene.

      The identification of genes causing susceptibility to hypertension is important, since it
      would give new tools for the diagnosis and enable better etiological classification and
      specific treatment of the disease. Finland is an ideal place for a study like this because of
      the genetic homogeneity of the population, the relatively high prevalence of the disease and
      the established protocols for the treatment and follow-up of hypertension in public health
      care.

      The molecular genetic studies on hypertension performed so far (by 1999) have primarily been
      association studies, which are based on case-control classification and may produce erroneous
      results. Particularly, a reliable phenotyping of cases and controls has been difficult.
      Consequently, more attention should be paid to the phenotyping of patients, and novel
      intermediate phenotypes characteristic of certain subtypes of hypertension should be used to
      facilitate the search for hypertension genes. The innovation of this study is to use the
      response to antihypertensive therapy as an intermediate phenotype.

      In the study, each subject uses one of four antihypertensive drugs, each as a monotherapy in
      a rotational fashion, for 28 days in a randomized order. The antihypertensive drugs to be
      tested include a thiazide diuretic, a beta-adrenergic antagonist, an angiotensin-II receptor
      antagonist and a calcium channel blocker. The drugs that are selected for the study are
      "typical" representatives of their groups and long-acting, and the dosages are sufficient but
      well tolerable. The study design does not necessitate the use of equipotent doses of the
      various agents, since the study is not designed to compare the antihypertensive effectiveness
      of the study drugs or, due to the short treatment periods, their effects on clinical
      endpoints.
    

Intervention name(s): Amlodipine; Bisoprolol; Hydrochlorothiazide; Losartan; Placebo
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): Treatment for four weeks. Dose: 5 mg o.d.; Treatment for four weeks. Dose: 5 mg o.d.; Treatment for four weeks. Dose: 25 mg o.d.; Treatment for four weeks. Dose: 50 mg o.d.; Treatment for four weeks. Dose: 1 tablet per day.
Intervention MeSH terms: Losartan; Amlodipine; Hydrochlorothiazide; Bisoprolol
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: The design of the study is a randomized placebo-controlled cross-over study. The study starts with a run-in placebo period lasting for four weeks. The four monotherapy treatment periods last for four weeks and they are separated by placebo periods lasting also for four weeks. Randomization occurs after the first placebo period in blocks of 24 (all possible drug sequences).
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment