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

Condition(s) targeted: Metabolic Syndrome

Intervention: Rosiglitazone (Drug)

Phase: Phase 3

Status: Not yet recruiting

Sponsored by: Baker Heart Research Institute

Official(s) and/or principal investigator(s):
Nora E Straznicky, PhD, MPH, Principal Investigator, Affiliation: Baker Heart Research Institute

Overall contact:
Nora E Straznicky, PhD, MPH, Phone: 61 3 8532 1371, Email: Nora.Straznicky@baker.edu.au

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).

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

Study design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Efficacy Study

Primary outcome: Sympathetic nervous system activity, measured as muscle sympathetic nervous activity and whole-body noradrenaline spillover

Secondary outcome: Baroreflex function, adrenoceptor expression

Detailed description: 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.

Minimum age: 45 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

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.

Nora E Straznicky, PhD, MPH, Phone: 61 3 8532 1371, Email: Nora.Straznicky@baker.edu.au

Baker Heart Research Institute, Melbourne, Victoria 8008, Australia

Related publications:

Esler M, Straznicky N, Eikelis N, Masuo K, Lambert G, Lambert E. Mechanisms of sympathetic activation in obesity-related hypertension. Hypertension. 2006 Nov;48(5):787-96. Epub 2006 Sep 25. No abstract available.

Straznicky NE, Lambert EA, Lambert GW, Masuo K, Esler MD, Nestel PJ. Effects of dietary weight loss on sympathetic activity and cardiac risk factors associated with the metabolic syndrome. J Clin Endocrinol Metab. 2005 Nov;90(11):5998-6005. Epub 2005 Aug 9.

Starting date: January 2008
Ending date: December 2008
Last updated: October 30, 2007