Effects of Pioglitazone Treatment on Sympathetic Nervous System Function in Metabolic Syndrome Obesity
Mechanisms of Sympathetic Overactivity in the Metabolic Syndrome: Effects of Reversing Insulin Resistance by Drug Treatment
1 other identifier
interventional
44
1 country
1
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_3
Started Nov 2008
Typical duration for phase_3
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 6, 2006
CompletedFirst Posted
Study publicly available on registry
December 7, 2006
CompletedStudy Start
First participant enrolled
November 1, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
February 1, 2013
CompletedJanuary 17, 2013
January 1, 2013
4.3 years
December 6, 2006
January 16, 2013
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Sympathetic nervous system activity, measured as muscle sympathetic nervous activity and whole-body noradrenaline spillover
12 weeks treatment
Secondary Outcomes (1)
Baroreflex function, adrenoceptor expression
12 weeks treatment
Study Arms (2)
Pioglitazone
ACTIVE COMPARATORpioglitazone 15 mg for 6 weeks followed by 30 mg for 6 weeks
sugar pill
PLACEBO COMPARATORPlacebo comparator
Interventions
15 mg per day for 6 weeks and 30 mg per day for further 6 weeks
One capsule daily for 6 weeks followed by two capsules per day for next 6 weeks
Eligibility Criteria
You may qualify if:
- Males and females aged 45-65 years,
- non-smokers,
- HOMA index \> 2.5 and
- who meet ATP III criteria for the metabolic syndrome
You may not qualify if:
- History of diabetes,
- previous MI, stroke, heart failure, impaired hepatic or renal function.
- Inability to cease medications which may affect study parameters.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Baker Heart Research Institute
Melbourne, Victoria, 8008, Australia
Related Publications (6)
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.
PMID: 17000932BACKGROUNDStraznicky 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.
PMID: 16091482BACKGROUNDStraznicky 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.
PMID: 26297500DERIVEDStraznicky 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.
PMID: 25827058DERIVEDStraznicky 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.
PMID: 25590214DERIVEDStraznicky 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.
PMID: 24937541DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Nora E Straznicky, PhD, MPH
Baker Heart Research Institute
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Dr
Study Record Dates
First Submitted
December 6, 2006
First Posted
December 7, 2006
Study Start
November 1, 2008
Primary Completion
February 1, 2013
Study Completion
February 1, 2013
Last Updated
January 17, 2013
Record last verified: 2013-01