A Study on Molecular Genetics of Drug Responsiveness in Essential Hypertension

Hypertension Clinical Trial

— GENRES  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03276598
• Other study ID #: GENRES
• Status: Completed
• Phase: Phase 4
• First received: September 6, 2017
• Last updated: September 8, 2017
• Start date: November 25, 1999
• Est. completion date: April 1, 2004

Study information

• Verified date: September 2017
• Source: Helsinki University Central Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 233
• Est. completion date: April 1, 2004
• Est. primary completion date: April 1, 2004
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 35 Years to 59 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hypertension
• Pharmacogenetics

Intervention

Drug:
• Amlodipine
Treatment for four weeks. Dose: 5 mg o.d.
• Bisoprolol
Treatment for four weeks. Dose: 5 mg o.d.
• Hydrochlorothiazide
Treatment for four weeks. Dose: 25 mg o.d.
• Losartan
Treatment for four weeks. Dose: 50 mg o.d.
• Placebo
Treatment for four weeks. Dose: 1 tablet per day.

Locations

Country	Name	City	State
Finland	Helsinki University Central Hospital	Helsinki

Sponsors (1)

Lead Sponsor	Collaborator
Helsinki University Central Hospital

Country where clinical trial is conducted

Finland, 

References & Publications (3)

Hiltunen TP, Donner KM, Sarin AP, Saarela J, Ripatti S, Chapman AB, Gums JG, Gong Y, Cooper-DeHoff RM, Frau F, Glorioso V, Zaninello R, Salvi E, Glorioso N, Boerwinkle E, Turner ST, Johnson JA, Kontula KK. Pharmacogenomics of hypertension: a genome-wide, — View Citation

Hiltunen TP, Suonsyrjä T, Hannila-Handelberg T, Paavonen KJ, Miettinen HE, Strandberg T, Tikkanen I, Tilvis R, Pentikäinen PJ, Virolainen J, Kontula K. Predictors of antihypertensive drug responses: initial data from a placebo-controlled, randomized, cros — View Citation

Suonsyrjä T, Hannila-Handelberg T, Paavonen KJ, Miettinen HE, Donner K, Strandberg T, Tikkanen I, Tilvis R, Pentikäinen PJ, Kontula K, Hiltunen TP. Laboratory tests as predictors of the antihypertensive effects of amlodipine, bisoprolol, hydrochlorothiazi — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Blood pressure	Change in blood pressure	4 weeks