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Obesity is a major risk factor for the development of hypertension. Based on population studies, risk estimates indicate that at least two-thirds of the prevalence of hypertension can be directly attributed to obesity. Obesity per se is commonly associated with activation of the sympathetic nervous system with a predominant increase in sympathetic outflow to the kidneys and the peripheral vasculature and there is now conclusive evidence that heightened sympathetic nerve activity is a major contributor to the elevation in blood pressure associated with obesity, particularly in young subjects. In line with these findings, dietary weight loss has repeatedly been demonstrated to result in reduced sympathetic nerve activity and lower blood pressure levels.
Several lines of evidence have well documented the significant role of SNS activation in obesity associated hypertension and target organ damage. Weight loss is the preferred treatment option for obesity and its consequences and reduces both SNS activation and blood pressure. In the real world however, weight loss maintenance is rarely achieved in obese patients highlighting the urgent need for alternative treatment strategies. Given the crucial involvement of SNS activation in various aspects of the obesity related increase in blood pressure, target organ damage and cardiovascular risk, the use of sympatho-inhibitory agents at an early stage is an obvious choice.
The investigators therefore plan to examine the effects of the centrally sympatholytic agent moxonidine on blood pressure and the morning surge in blood pressure, sympathetic activity, regression of early target organ damage (heart, kidney and endothelium), metabolic and inflammatory markers in young obese subjects with hypertension in a randomized, double-blind clinical trial with the angiotensin receptor blocker irbesartan as an active comparator to achieve similar blood pressure reductions in both groups. The investigators hypothesize that moxonidine treatment will result in significant improvements in these outcome parameters and beneficial effects beyond simple blood pressure reduction.
Findings from this study could pave the way for an early and pathophysiology- tailored treatment strategy of obesity related hypertension and its detrimental consequences.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Moxonidine | Experimental |
| |
| Irbesartan | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Moxonidine | Drug | 0.2mg/day for 2 weeks, 0.4mg/day for 6 months |
|
| Measure | Description | Time Frame |
|---|---|---|
| Microneurography (nerve recording) | Microneurography technique will be performed on participants at baseline and 6 months post treatment to see if moxonidine has any effect in the reduction of sympathetic activiry. | 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Blood test | Blood samples will be taken from antecubital vein for biochemical analyses purposes. The sampling will take place at baseline and at 6 months visit. | 6 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Markus Schlaich | Contact | 03 8532 1502 | markus.schlaich@bakeridi.edu.au |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| BakerIDI Heart and Diabetes Institute | Recruiting | Prahran | Victoria | 3004 | Australia |
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| Irbesartan | Drug | 75 mg/day for 2 weeks and then 150 mg/day for 24 weeks. |
|
| ID | Term |
|---|---|
| D056128 | Obesity, Abdominal |
| D006973 | Hypertension |
| D003863 | Depression |
| ID | Term |
|---|---|
| D009765 | Obesity |
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
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| ID | Term |
|---|---|
| C043482 | moxonidine |
| D000077405 | Irbesartan |
| ID | Term |
|---|---|
| D001713 | Biphenyl Compounds |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D013141 | Spiro Compounds |
| D013777 | Tetrazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011083 | Polycyclic Compounds |
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