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

September 8, 2017 updated by: Kimmo Kontula, Helsinki University Central Hospital

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

233

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Finland
      • Helsinki, Finland
        • Helsinki University Central Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

35 years to 59 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Blood pressure
Time Frame: 4 weeks
Change in blood pressure
4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Helsinki University Central Hospital

Investigators

  • Principal Investigator: Kimmo K Kontula, Professor, Helsinki University Central Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

November 25, 1999

Primary Completion (ACTUAL)

April 1, 2004

Study Completion (ACTUAL)

April 1, 2004

Study Registration Dates

First Submitted

September 6, 2017

First Submitted That Met QC Criteria

September 6, 2017

First Posted (ACTUAL)

September 8, 2017

Study Record Updates

Last Update Posted (ACTUAL)

September 11, 2017

Last Update Submitted That Met QC Criteria

September 8, 2017

Last Verified

September 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GENRES

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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