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Trial record 68 of 73 for:    HYDROCHLOROTHIAZIDE AND LOSARTAN

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

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ClinicalTrials.gov Identifier: NCT03276598
Recruitment Status : Completed
First Posted : September 8, 2017
Last Update Posted : September 11, 2017
Sponsor:
Information provided by (Responsible Party):
Kimmo Kontula, Helsinki University Central Hospital

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 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.


Condition or disease Intervention/treatment Phase
Hypertension Pharmacogenetics Drug: Amlodipine Drug: Bisoprolol Drug: Hydrochlorothiazide Drug: Losartan Drug: Placebo Phase 4

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.


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Study Type : Interventional  (Clinical Trial)
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).
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 : November 25, 1999
Actual Primary Completion Date : April 1, 2004
Actual Study Completion Date : April 1, 2004

Resource links provided by the National Library of Medicine


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.




Primary Outcome Measures :
  1. Blood pressure [ Time Frame: 4 weeks ]
    Change in blood pressure



Information from the National Library of Medicine

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Ages Eligible for Study:   35 Years to 59 Years   (Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Based on self-representation of gender identity
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03276598


Locations
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Finland
Helsinki University Central Hospital
Helsinki, Finland
Sponsors and Collaborators
Helsinki University Central Hospital
Investigators
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Principal Investigator: Kimmo K Kontula, Professor Helsinki University Central Hospital

Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Kimmo Kontula, Professor, Helsinki University Central Hospital
ClinicalTrials.gov Identifier: NCT03276598     History of Changes
Other Study ID Numbers: GENRES
First Posted: September 8, 2017    Key Record Dates
Last Update Posted: September 11, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Additional relevant MeSH terms:
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Losartan
Hydrochlorothiazide
Hypertension
Essential Hypertension
Vascular Diseases
Cardiovascular Diseases
Amlodipine
Bisoprolol
Antihypertensive Agents
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Vasodilator Agents
Anti-Arrhythmia Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Diuretics
Natriuretic Agents
Sodium Chloride Symporter Inhibitors
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents