E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hypertension in subjects with abdominal obesity and the metabolic syndrome |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10059179 |
E.1.2 | Term | Abdominal obesity |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052066 |
E.1.2 | Term | Metabolic syndrome |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020772 |
E.1.2 | Term | Hypertension |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065941 |
E.1.2 | Term | Central obesity |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare changes in endothelial function after 8 weeks of treatment with aliskiren, moxonidine and hydrochlorothiazide in patients with obesity related hypertension. |
|
E.2.2 | Secondary objectives of the trial |
to compare changes in the following parameters in patients with obesity related hypertension after 8 weeks of treatment with aliskiren, moxonidine and HCTZ: adipose tissue function, lipid metabolism, insulin sensitivity, blood pressure, oxidative stress, systemic inflammation, arterial stiffness, RAS-activity, SNS-activity and renal sodium handling. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patient is a male of 30-70 years of age on the day of signing informed consent.
All patients should fulfil the diagnostic criterion of abdominal adiposity: waist circumference >/= 102 cm. The waist circumference is measured halfway between the lower rib and iliac crest in standing position.
All patients should fulfil the diagnostic criterium for hypertension: - SBP >/= 130 mmHg and/or DBP >/= 85 mmHg during both visits. Blood pressure is assessed by office readings in accordance with current guidelines for hypertension diagnosis. The patient needs to be seated some minutes before and during the measurement. The cuff size should be adjusted to the patients’ arm circumference and needs to be on the same height level as the patients’ sternum during the measurements. Blood pressure is determined to a 2 mmHg accuracy-level. Blood pressure is measured on both arms during the first visit. In both measurements differ more than 10 mmHg, the highest value is taken. After at least 15 seconds, the measurement is repeated during the same visit. The highest mean of the two measurements on the same arm is considered as the actual blood pressure value.
Patients should fulfil one or more of the following criteria to meet the definition of the metabolic syndrome: - Hypertriglyceridemia (serum triglycerides > 1.7 mmol/L); - Low High-density lipoprotein (HDL)-cholesterol (serum HDL-cholesterol < 1.04 mmol/L); - High fasting glucose (fasting serum glucose > 5.6 mmol/L).
Patient understands the study procedures, alternative treatments available, and risks involved with the study and voluntarily agrees to participate by giving written informed consent. |
|
E.4 | Principal exclusion criteria |
SBP > 180 mmHg and/or DBP > 110 mmHg during one or more screening measurements and/or use of more than one type of antihypertensive medication.
Ten year cardiovascular mortality risk according to the SCORE-risk model > 10%.
BMI > 35 kg/m2
Current smoking or smoking during the previous 3 months
Use of “recreational” or illicit drugs
Recent history (within the last year) of alcohol abuse or dependence.
History of hypersensitivity reactions or intolerance to any (components of) medication used in this trial.
Current / recent participation (within 30 days of signing informed consent) in a study with an investigational compound or device.
Laboratory values as listed below: - Hemoglobin (Hb) < 8,6 mmol/L - TSH <0.3 mcIU/mL or > 5.0 mcIU/mL - Potassium < 3,8 mmol/L or > 5,0 mmol/L - Sodium < 136 mmol/L or > 146 mmol/L - MDRD < 60 mL/min/1,73m2
Medical conditions as listed below: - Secondary hypertension - Congestive Heart Failure - Atherosclerotic vascular disease. (As per NCEP ATP III and AHA/ACC Guidelines: Established atherosclerotic vascular disease includes history of myocardial infarction, stable angina, coronary artery procedures (angioplasty or bypass surgery) or evidence of clinically significant myocardial ischemia. Other atherosclerotic vascular disease includes clinical manifestations of non-coronary forms of atherosclerotic disease (peripheral arterial disease, cerebrovascular disease, abdominal aortic aneurysm, and carotid artery disease [transient ischemic attacks or stroke of carotid origin or >50% obstruction of a carotid artery]). - Cardiac arrhythmia’s, for example bradycardia, atrial fibrillation, sick-sinus syndrome, sinoatrial block, atriovertricular block or any other arrhythmia. - Obstructive sleep apnea syndrome (OSAS) or a score of 10 or higher on the Epworth Sleepiness Scale questionnaire. - Type 2 diabetes mellitus - Serious liver function disorders (Child-Pugh-Class C). - COPD (GOLD classification of severity 2 or higher) - Celiac disease or other significant intestinal malabsorption - Malignancy ≤ 5 years prior to signing informed consent, except for adequately treated basal or squamous cell skin cancer or in situ cervical cancer. - Mental instability or major psychiatric illness - Polyneuropathy or clinical suspicion for autonomic nervous system dysfunction. - Any diseases that would limit or complicate study evaluation or participation. - Any diseases or screening abnormalities that call for treatment that can not be postponed until after the study period without causing harm.
Any concomitant medication, particularly antihypertensive co-medication, glucose lowering medication, lipid lowering drugs, systemic corticosteroids and vitamin C or E supplements, but also any other kinds of drugs, including over the counter medication. Exceptions can be made for the following categories of drugs: - paracetamol; - proton-pump inhibitors; - topical creams and unguents that do not lead to uptake of any of the active components into the circulation (in case of steroid creams: class II or lower); - inhalation medication, nasal sprays and eye drops that do not lead to uptake of any of the active components into the circulation. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Mean intrapersonal changes in endothelial function (FMD), serum adipokine concentrations, serum lipid concentrations, HOMA, mean 24-hour SBP/DBP, mean day/night time SBP/DBP, central blood pressure (PWA), serum and urine concentrations of markers of oxidative stress, serum concentrations of markers of systemic inflammation, arterial stiffness (PWV, PWA), RAS-hormone concentrations, MSNA, HRV, fractional sodium excretion. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
End of the last patients' tapering period following the last study visit. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |