Clinical trial NCT00408850: Effects of Pioglitazone Treatment on Sympathetic Nervous System Function in Metabolic Syndrome Obesity
Official title: Mechanisms of Sympathetic Overactivity in the Metabolic Syndrome: Effects of Reversing Insulin Resistance by Drug Treatment
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Metabolic Syndrome
Keywords: sympathetic nervous system, pioglitazone, metabolic syndrome
Lead sponsor: Baker Heart Research Institute
Sponsor class: OTHER
Collaborators: name: National Heart Foundation, Australia
First posted: 2006-12-07
Enrollment: 44
Sex: ALL
Minimum age (years): 45
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

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.

Eligibility 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.

Primary outcomes:
measure: Sympathetic nervous system activity, measured as muscle sympathetic nervous activity and whole-body noradrenaline spillover
timeFrame: 12 weeks treatment
Secondary outcomes:
measure: Baroreflex function, adrenoceptor expression
timeFrame: 12 weeks treatment
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Baker Heart Research Institute
state: Victoria
Study officials:
affiliation: Baker Heart Research Institute
name: Nora E Straznicky, PhD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1161/01.HYP.0000242642.42177.49. Epub 2006 Sep 25. No abstract available.
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. doi: 10.1210/jc.2005-0961. Epub 2005 Aug 9.
citation: Straznicky NE, Grima MT, Sari CI, Lambert EA, Phillips SE, Eikelis N, Kobayashi D, Hering D, Mariani JA, Dixon JB, Nestel PJ, Karapanagiotidis S, Schlaich MP, Lambert GW. Reduction in peripheral vascular resistance predicts improvement in insulin clearance following weight loss. Cardiovasc Diabetol. 2015 Aug 22;14:113. doi: 10.1186/s12933-015-0276-2.
citation: Straznicky NE, Grima MT, Sari CI, Eikelis N, Lambert GW, Nestel PJ, Richards K, Dixon JB, Schlaich MP, Lambert EA. Pioglitazone treatment enhances the sympathetic nervous system response to oral carbohydrate load in obese individuals with metabolic syndrome. Metabolism. 2015 Jul;64(7):797-803. doi: 10.1016/j.metabol.2015.03.006. Epub 2015 Mar 18.
citation: Straznicky NE, Grima MT, Lambert EA, Sari CI, Eikelis N, Nestel PJ, Phillips SE, Hering D, Karapanagiotidis S, Dixon JB, Schlaich MP, Lambert GW. Arterial norepinephrine concentration is inversely and independently associated with insulin clearance in obese individuals with metabolic syndrome. J Clin Endocrinol Metab. 2015 Apr;100(4):1544-50. doi: 10.1210/jc.2014-3796. Epub 2015 Jan 15.
citation: Straznicky NE, Grima MT, Sari CI, Eikelis N, Lambert GW, Nestel PJ, Karapanagiotidis S, Wong C, Richards K, Marusic P, Dixon JB, Schlaich MP, Lambert EA. A randomized controlled trial of the effects of pioglitazone treatment on sympathetic nervous system activity and cardiovascular function in obese subjects with metabolic syndrome. J Clin Endocrinol Metab. 2014 Sep;99(9):E1701-7. doi: 10.1210/jc.2014-1976. Epub 2014 Jun 17.