Effects of Pioglitazone Treatment on Sympathetic Nervous System Function in Metabolic Syndrome Obesity

Study Overview
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Brief Summary
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An abdominal distribution of fat is associated with the greatest heart disease risk, because commonly, several risk factors of metabolic origin cluster in these individuals. When this occurs the condition is called the 'metabolic syndrome'. Increased activity of the sympathetic nervous system resulting in enhanced release of the stress hormone 'noradrenaline', may be one mechanism by which adverse cardiovascular and metabolic sequela of the metabolic syndrome might be mediated. Impaired insulin action may be one factor contributing to increased noradrenaline release. The aim of this Study is to determine whether treatment with a drug called pioglitazone which is known to improve insulin action, results in reduced sympathetic nervous system activity and stress hormone release when compared to treatment with a dummy drug (placebo).

Detailed Description
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The rapidly growing burden of obesity together with a population that is becoming older raises the importance of effective strategies for the primary prevention and treatment of the metabolic syndrome in order to combat the epidemic of type 2 diabetes and to reduce the increased risk of cardiovascular mortality. Increased sympathetic nervous system activity may participate in the pathogenesis and complications of the metabolic syndrome. This Study will use a randomised controlled design to evaluate the effects of pioglitazone treatment on sympathetic activity in middle-aged subjects with the metabolic syndrome.The results will generate new information on the neuroadrenergic effects of thiazolidinediones in this clinical setting. This is relevant to the understanding of the pathophysiology of the metabolic syndrome and to its clinical management.

Official Title
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Mechanisms of Sympathetic Overactivity in the Metabolic Syndrome: Effects of Reversing Insulin Resistance by Drug Treatment

Conditions
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Metabolic Syndrome

Intervention / Treatment
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* Drug: Pioglitazone
* Drug: sugar pill


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females aged 45-65 years, non-smokers, HOMA index > 2.5 and who meet ATP III criteria for the metabolic syndrome Exclusion Criteria: History of diabetes, previous MI, stroke, heart failure, impaired hepatic or renal function. Inability to cease medications which may affect study parameters.

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pioglitazone<br>pioglitazone 15 mg for 6 weeks followed by 30 mg for 6 weeks | Drug: Pioglitazone<br>* 15 mg per day for 6 weeks and 30 mg per day for further 6 weeks<br>* Other names: Actos;|
| Placebo Comparator: sugar pill<br>Placebo comparator | Drug: sugar pill<br>* One capsule daily for 6 weeks followed by two capsules per day for next 6 weeks<br>* Other names: Lactose;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sympathetic nervous system activity, measured as muscle sympathetic nervous activity and whole-body noradrenaline spillover |  | 12 weeks treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baroreflex function, adrenoceptor expression |  | 12 weeks treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sympathetic nervous system, pioglitazone, metabolic syndrome