Metabolic SyndromePhase 3NCT00408850
Effects of Pioglitazone Treatment on Sympathetic Nervous System Function in Metabolic Syndrome Obesity
A Phase 3 study testing Pioglitazone and sugar pill in people with Metabolic Syndrome, run by Baker Heart Research Institute at 1 site in Australia.
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'. Read more about this study
- Who is it for?
- Ages 45 to 65 years
- Conditions the study is for
- Metabolic Syndrome
- What is being tested?
- Pioglitazone and sugar pill
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- 1 siteAustralia
- Study dates
- Nov 2008to Feb 2013
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males and females aged 45-65 years,
- non-smokers,
- HOMA index > 2.5 and
- who meet ATP III criteria for the metabolic syndrome
Who cannot join
- History of diabetes,
- previous MI, stroke, heart failure, impaired hepatic or renal function.
- Inability to cease medications which may affect study parameters.
Trial locations and contacts
1 site in 1 country.
Australia1 site, 1 recruiting
- Recruiting
Baker Heart Research Institute
Melbourne, Victoria, 8008
Nora E Straznicky, PhD MPH
About this study
Official title: Mechanisms of Sympathetic Overactivity in the Metabolic Syndrome: Effects of Reversing Insulin Resistance by Drug Treatment
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).
Read the 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.
- Conditions
- Metabolic Syndrome
- Being tested
- Pioglitazone, sugar pill
- Keywords
- sympathetic nervous system, pioglitazone, metabolic syndrome
- Medical subject headings
- Metabolic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PioglitazoneDrug
Also called Actos
15 mg per day for 6 weeks and 30 mg per day for further 6 weeks
sugar pillDrug
Also called Lactose
One capsule daily for 6 weeks followed by two capsules per day for next 6 weeks
| Study group | Role | What they receive |
|---|---|---|
| Pioglitazone | Active comparator | pioglitazone 15 mg for 6 weeks followed by 30 mg for 6 weeks Receives: Drug: Pioglitazone |
| sugar pill | Placebo comparator | Placebo comparator Receives: Drug: sugar pill |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sympathetic nervous system activity, measured as muscle sympathetic nervous activity and whole-body noradrenaline spillover
Measured: 12 weeks treatment
Secondary outcomes (1)
Baroreflex function, adrenoceptor expression
Measured: 12 weeks treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2006 (estimated)
- Study startNov 2008
- Primary completionFeb 2013 (estimated)
- Study completionFeb 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Metabolic SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 44 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Baker Heart Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart Foundation, Australia
- Responsible party
- Principal investigator, Nora E. Straznicky, Baker Heart Research Institute
- Investigators
- Nora E Straznicky, PhD, MPH, Principal investigator, Baker Heart Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00408850
- Sponsor's protocol ID
- G 06M 2610
- Status last verified
- Jan 2013
- First submitted
- 6 Dec 2006
- Last updated
- 17 Jan 2013
- Results posted
- No
- Data monitoring committee
- No
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. doi: 10.1161/01.HYP.0000242642.42177.49. Epub 2006 Sep 25. No abstract available.
PubMed 17000932Straznicky 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.
PubMed 16091482Straznicky 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.
PubMed 26297500Straznicky 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.
PubMed 25827058Straznicky 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.
PubMed 25590214Straznicky 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.
PubMed 24937541
Study at a glance
From the registry record, last updated by the sponsor on 17 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms of Sympathetic Overactivity in the Metabolic Syndrome: Effects of Reversing Insulin Resistance by Drug Treatment
- ClinicalTrials.gov ID
- NCT00408850
- Acronym / sponsor ID
- G 06M 2610
- Conditions
- Metabolic Syndrome
- Keywords
- sympathetic nervous system, pioglitazone, metabolic syndrome
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 44 participants (estimated)
- Lead sponsor
- Baker Heart Research InstituteUniversity, hospital or other
- Collaborators
- National Heart Foundation, Australia
- Study start
- Nov 2008
- Primary completion
- Feb 2013 (estimated)
- Study completion
- Feb 2013 (estimated)
- First posted
- 7 Dec 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pioglitazone | Active comparator | Drug: Pioglitazonepioglitazone 15 mg for 6 weeks followed by 30 mg for 6 weeks |
| sugar pill | Placebo comparator | Drug: sugar pillPlacebo comparator |
Who may qualify
- Ages
- 45 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Males and females aged 45-65 years,
- non-smokers,
- HOMA index > 2.5 and
- who meet ATP III criteria for the metabolic syndrome
Key exclusion criteria (3 listed)
- History of diabetes,
- previous MI, stroke, heart failure, impaired hepatic or renal function.
- Inability to cease medications which may affect study parameters.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PioglitazoneAlso: Actos15 mg per day for 6 weeks and 30 mg per day for further 6 weeks | Drug | Pioglitazone |
| sugar pillAlso: LactoseOne capsule daily for 6 weeks followed by two capsules per day for next 6 weeks | Drug | sugar pill |
Primary outcome
Sympathetic nervous system activity, measured as muscle sympathetic nervous activity and whole-body noradrenaline spillover
Time frame: 12 weeks treatment
1 secondary outcome
Baroreflex function, adrenoceptor expression
Time frame: 12 weeks treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jan 2013.
- Background: PubMed 17000932Esler 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.
- Background: PubMed 16091482Straznicky 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.
- Derived from this study: PubMed 26297500Straznicky 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.
- Derived from this study: PubMed 25827058Straznicky 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.
- Derived from this study: PubMed 25590214Straznicky 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.
- Derived from this study: PubMed 24937541Straznicky 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nora E Straznicky, PhD, MPH principal investigator
Baker Heart Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pioglitazone and sugar pill in people with Metabolic Syndrome, run by Baker Heart Research Institute at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Nora E Straznicky, PhD, MPH (61 3 8532 1371, Nora.Straznicky@bakeridi.edu.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sympathetic nervous system activity, measured as muscle sympathetic nervous activity and whole-body noradrenaline spillover (time frame: 12 weeks treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00408850, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jan 2013.