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

Metabolic Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00408850
• Other study ID #: G 06M 2610
• Status: Recruiting
• Phase: Phase 3
• First received: December 6, 2006
• Last updated: January 16, 2013
• Start date: November 2008
• Est. completion date: February 2013

Study information

• Verified date: January 2013
• Source: Baker Heart Research Institute
• Contact: Nora E Straznicky, PhD, MPH
• Phone: 61 3 8532 1371
• Email: Nora.Straznicky[@]bakeridi.edu.au
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 44
• Est. completion date: February 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 45 Years to 65 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Metabolic Syndrome
• Metabolic Syndrome X
• Syndrome

Intervention

Drug:
• Pioglitazone
15 mg per day for 6 weeks and 30 mg per day for further 6 weeks
• sugar pill
One capsule daily for 6 weeks followed by two capsules per day for next 6 weeks

Locations

Country	Name	City	State
Australia	Baker Heart Research Institute	Melbourne	Victoria

Sponsors (2)

Lead Sponsor	Collaborator
Baker Heart Research Institute	National Heart Foundation, Australia

Country where clinical trial is conducted

Australia, 

References & Publications (2)

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. Review. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sympathetic nervous system activity, measured as muscle sympathetic nervous activity and whole-body noradrenaline spillover		12 weeks treatment	No
Secondary	Baroreflex function, adrenoceptor expression		12 weeks treatment	No