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A Study on Molecular Genetics of Drug Responsiveness in Essential Hypertension (GENRES)

H

Helsinki University Central Hospital (HUCH)

Status and phase

Completed
Phase 4

Conditions

Hypertension
Pharmacogenetics

Treatments

Drug: Amlodipine
Drug: Losartan
Drug: Placebo
Drug: Hydrochlorothiazide
Drug: Bisoprolol

Study type

Interventional

Funder types

Other

Identifiers

Details and patient eligibility

About

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.

Full 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.

Enrollment

233 patients

Sex

Male

Ages

35 to 59 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

  • essential hypertension diagnosed on an earlier occasion or during the present study (three diastolic blood pressure readings >=95 mmHg on separate occasions are required).

Exclusion Criteria (before and during the study):

  • usage of three or more antihypertensive drugs
  • secondary hypertension
  • left ventricular hypertrophy
  • drug-treated diabetes mellitus
  • coronary heart disease
  • stroke and other disorders of cerebral circulation
  • renal disease
  • obstructive pulmonary disease
  • a disease treated with corticosteroids
  • a disease with drug treatment potentially influencing blood pressure levels
  • significant obesity (BMI >=32 kg/m2)
  • allergic reaction towards any of the study drugs
  • The patient is excluded from the study if his blood pressure level rises to 200/120 mmHg or above during the study.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Crossover Assignment

Masking

Quadruple Blind

233 participants in 5 patient groups, including a placebo group

Amlodipine
Active Comparator group
Description:
One of the four monotherapy treatment periods.
Treatment:
Drug: Amlodipine
Bisoprolol
Active Comparator group
Description:
One of the four monotherapy treatment periods.
Treatment:
Drug: Bisoprolol
Hydrochlorothiazide
Active Comparator group
Description:
One of the four monotherapy treatment periods.
Treatment:
Drug: Hydrochlorothiazide
Losartan
Active Comparator group
Description:
One of the four monotherapy treatment periods.
Treatment:
Drug: Losartan
Placebo
Placebo Comparator group
Description:
Placebo treatment period.
Treatment:
Drug: Placebo

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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