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

Sponsor

Helsinki University Central Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT03276598

Collaborator

(none)

233

Enrollment

Location

Arms

52.2

Actual Duration (Months)

4.5

Patients Per Site Per Month

Study Details

Study Description

Brief 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 innovation of this study is to use the response to antihypertensive therapy as an intermediate phenotype.

Condition or Disease	Intervention/Treatment	Phase
Hypertension Pharmacogenetics	Drug: Amlodipine Drug: Bisoprolol Drug: Hydrochlorothiazide Drug: Losartan Drug: Placebo	Phase 4

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

233 participants

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).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)

Masking Description:

The placebo tablets and drugs are packed in similar gelatin capsules.

Primary Purpose:

Treatment

Official Title:

A Randomised Double-blind Cross-over Single-centre Study on Molecular Genetics of Drug Responsiveness in Essential Hypertension

Actual Study Start Date :

Nov 25, 1999

Actual Primary Completion Date :

Apr 1, 2004

Actual Study Completion Date :

Apr 1, 2004

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Amlodipine One of the four monotherapy treatment periods.	Drug: Amlodipine Treatment for four weeks. Dose: 5 mg o.d.
Active Comparator: Bisoprolol One of the four monotherapy treatment periods.	Drug: Bisoprolol Treatment for four weeks. Dose: 5 mg o.d.
Active Comparator: Hydrochlorothiazide One of the four monotherapy treatment periods.	Drug: Hydrochlorothiazide Treatment for four weeks. Dose: 25 mg o.d.
Active Comparator: Losartan One of the four monotherapy treatment periods.	Drug: Losartan Treatment for four weeks. Dose: 50 mg o.d.
Placebo Comparator: Placebo Placebo treatment period.	Drug: Placebo Treatment for four weeks. Dose: 1 tablet per day.

Outcome Measures

Primary Outcome Measures

Blood pressure [4 weeks]
Change in blood pressure

Eligibility Criteria

Criteria

Ages Eligible for Study:

35 Years to 59 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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.