Congestive Heart FailurePhase 4TAYSIDENCT00473876
Metformin in Insulin Resistant Left Ventricular (LV) Dysfunction (TAYSIDE Trial)
A Phase 4 study testing Metformin in people with Congestive Heart Failure and Insulin Resistance, run by University of Dundee at 1 site in United Kingdom.
Trial summary
Will metformin improve exercise capacity in chronic heart failure patients who has insulin resistance (pre-diabetic- means before they become diabetic)? Read more about this study
- Who is it for?
- Ages 25 to 80 years
- Conditions the study is for
- Congestive Heart Failure, Insulin Resistance
- What is being tested?
- Metformin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 62 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Aug 2007to Apr 2009
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 25 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients aged 25-80 yrs with compensated CHF in NYHA functional I-III with evidence of insulin resistance [fasting insulin resistance index values of > 2.7 are said to have insulin resistance].
- Documented Left ventricular systolic dysfunction or LV ejection fraction < 35%
Who cannot join
- Elderly patients (aged >80 yrs);
- Patients with decompensated CHF (NYHA functional class IV and /or signs of decompensated CHF);
- Renal dysfunction (serum creatinine > 160 mmol/L);
- Patients who are unable to exercise including patients that will be excluded for reasons of safety or potential effects on exercise performance. Therefore, patients with angina or other cardiac or pulmonary symptoms potentially limiting exercise performance will be excluded.
- Systolic blood pressure >190 mmHg at rest or >250 mmHg with exercise or diastolic blood pressure >95 mmHg at rest or >105 mmHg with exercise will also be a reason for exclusion;
- Patients with underlying disease likely to limit life span and/or increase risk of interventions will be excluded i.e., cancer; cardiovascular disease .i.e., uncontrolled hypertension: SBP>180 mmHg or DBP, recent stroke, any severe chronic disease (including renal and hepatic disease).
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Medicine and Therapeutics, Ninewells Hospital
Dundee, Scotland, DD1 9SY
About this study
Official title: Metformin in Insulin Resistant LV Dysfunction, a Double-blind, Placebo-controlled Trial (TAYSIDE Trial)
Will metformin improve exercise capacity in chronic heart failure patients who has insulin resistance (pre-diabetic- means before they become diabetic)?
Read the detailed description
Exercise incapacity is one of the major debilitating symptoms of heart failure patients. Studies showed that heart failure patients will become insulin resistance (IR) or vice versa, severity of heart failure also correlates with the severity of insulin resistance. A recent study demonstrated that if we correct diabetic patient insulin resistance by giving them a drug to make them more sensitive to the effects of insulin, their exercise capacity improves. Therefore, we think that the same effects might happen in heart failure patients who have been identified to the insulin resistance by blood test. Insulin resistance means that they have not yet become diabetic and it is a stage the diabetic patients go through before they develop diabetes.
Therefore, we plan to use a drug called metformin (a diabetic drug), give it to heart failure patients who also have IR for 4 months and examine the effects before and after 4 months of treatment. It is a double blind control study, therefore, neither the examiner nor the patient know which drug they receive (either active drug- Metformin, or a placebo).
The main objective is to assess their exercise capacity using an exercise test called Innocor System. It is a bicycle based exercise test that involves patient breathing into a mouth piece before and during exercise in order for the machine to work out the maximum oxygen consumption and pumping power of the heart.
The other objectives of the trial are looking at the possible mechanisms of improving exercise capacity. We aim to answer the following questions by doing the following tests:
Does exercise capacity improve because of
- The effect of metformin on the heart? We will answer this question by doing an ultrasound scan of the heart (Echocardiography)
- The effects on the blood vessels? We plan to perform a test called flow-mediated dilatation, it is an ultrasound scan of the artery in the arm and also assess the blood flow in the skin using a test called Laser Doppler scan (small amount of medication will be delivered through a small electric current and the blood vessels response will be assessed using the laser doppler scan)
- The effects on the muscle? We will do a muscle biopsy looking at the enzymes activities in the muscle before and after taking 4 months of medication.
- Conditions
- Congestive Heart Failure, Insulin Resistance
- Being tested
- Metformin, Matched Placebo (Capsules)
- Keywords
- Chronic Heart Failure, Insulin Resistance, Metformin, Peak VO2
- Medical subject headings
- Heart Failure, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Started at 500mg bd for 2 weeks. If well tolerated, increase to 1000mg bd for 14 weeks
Matched Placebo (Capsules)Drug
Similar dosing regime as active comparator
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Receiving Metformin for 4 months Receives: Drug: Metformin |
| 2 | Placebo comparator | Matched Placebo for 4 months Receives: Drug: Matched Placebo (Capsules) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peak VO2
Peak VO2 after 4 months of intervention with either metformin or placebo. The Mean difference between baseline and after 4 months was analyzed using t-test comparing metformin and placebo.
Measured: 4 months
Secondary outcomes (1)
Possible Mechanisms That Can Explain the Improvement of Exercise Capacity
VE/VCO2 Slope, measurement of the abnormal ventilatory response to exercise identified by an increased slope of ventilation (L/min) vs. CO2 production (VE/VCO2) (L/min) to incremental workload
Measured: 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2007 (estimated)
- Study startAug 2007
- Primary completionApr 2009
- Study completionApr 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Congestive Heart FailureStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Dundee
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Aaron K Wong, University of Dundee
- Investigators
- Chim Lang, MD, FRCP, Principal investigator, University of Dundee, Scotland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00473876
- Sponsor's protocol ID
- WON001
- Acronym
- TAYSIDE
- Status last verified
- May 2013
- First submitted
- 15 May 2007
- Last updated
- 6 Jun 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Schiavone M, Gasperetti A, Vogler J, Compagnucci P, Laredo M, Breitenstein A, Gulletta S, Martinek M, Kaiser L, Tundo F, Palmisano P, Rovaris G, Curnis A, Kuschyk J, Biffi M, Tilz R, Di Biase L, Tondo C, Forleo GB; i-SUSI investigators. Sex differences among subcutaneous implantable cardioverter-defibrillator recipients: a propensity-matched, multicentre, international analysis from the i-SUSI project. Europace. 2024 May 2;26(5):euae115. doi: 10.1093/europace/euae115.
PubMed 38696701Schiavone M, Gasperetti A, Compagnucci P, Vogler J, Laredo M, Montemerlo E, Gulletta S, Breitenstein A, Ziacchi M, Martinek M, Casella M, Palmisano P, Kaiser L, Lavalle C, Calo L, Seidl S, Saguner AM, Rovaris G, Kuschyk J, Biffi M, Di Biase L, Dello Russo A, Tondo C, Della Bella P, Tilz R, Forleo GB; iSUSI investigators. Impact of ventricular tachycardia ablation in subcutaneous implantable cardioverter defibrillator carriers: a multicentre, international analysis from the iSUSI project. Europace. 2024 Mar 30;26(4):euae066. doi: 10.1093/europace/euae066.
PubMed 38584394Gasperetti A, Schiavone M, Ziacchi M, Vogler J, Breitenstein A, Laredo M, Palmisano P, Ricciardi D, Mitacchione G, Compagnucci P, Bisignani A, Angeletti A, Casella M, Picarelli F, Fink T, Kaiser L, Hakmi S, Calo L, Pignalberi C, Santini L, Lavalle C, Pisano E, Olivotto I, Tondo C, Curnis A, Dello Russo A, Badenco N, Steffel J, Love CJ, Tilz R, Forleo G, Biffi M. Long-term complications in patients implanted with subcutaneous implantable cardioverter-defibrillators: Real-world data from the extended ELISIR experience. Heart Rhythm. 2021 Dec;18(12):2050-2058. doi: 10.1016/j.hrthm.2021.07.008. Epub 2021 Jul 14.
PubMed 34271173Cameron AR, Morrison VL, Levin D, Mohan M, Forteath C, Beall C, McNeilly AD, Balfour DJ, Savinko T, Wong AK, Viollet B, Sakamoto K, Fagerholm SC, Foretz M, Lang CC, Rena G. Anti-Inflammatory Effects of Metformin Irrespective of Diabetes Status. Circ Res. 2016 Aug 19;119(5):652-65. doi: 10.1161/CIRCRESAHA.116.308445. Epub 2016 Jul 14.
PubMed 27418629Wong AK, Symon R, AlZadjali MA, Ang DS, Ogston S, Choy A, Petrie JR, Struthers AD, Lang CC. The effect of metformin on insulin resistance and exercise parameters in patients with heart failure. Eur J Heart Fail. 2012 Nov;14(11):1303-10. doi: 10.1093/eurjhf/hfs106. Epub 2012 Jun 27.
PubMed 22740509
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metformin in Insulin Resistant LV Dysfunction, a Double-blind, Placebo-controlled Trial (TAYSIDE Trial)
- ClinicalTrials.gov ID
- NCT00473876
- Acronym / sponsor ID
- TAYSIDE / WON001
- Conditions
- Congestive Heart Failure, Insulin Resistance
- Keywords
- Chronic Heart Failure, Insulin Resistance, Metformin, Peak VO2
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- University of DundeeUniversity, hospital or other
- Study start
- Aug 2007
- Primary completion
- Apr 2009 (actual)
- Study completion
- Apr 2009 (actual)
- First posted
- 16 May 2007 (estimated)
- Results
- Posted 6 Jun 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Will metformin improve exercise capacity in chronic heart failure patients who has insulin resistance (pre-diabetic- means before they become diabetic)?
Detailed description
Exercise incapacity is one of the major debilitating symptoms of heart failure patients. Studies showed that heart failure patients will become insulin resistance (IR) or vice versa, severity of heart failure also correlates with the severity of insulin resistance. A recent study demonstrated that if we correct diabetic patient insulin resistance by giving them a drug to make them more sensitive to the effects of insulin, their exercise capacity improves. Therefore, we think that the same effects might happen in heart failure patients who have been identified to the insulin resistance by blood test. Insulin resistance means that they have not yet become diabetic and it is a stage the diabetic patients go through before they develop diabetes.
Therefore, we plan to use a drug called metformin (a diabetic drug), give it to heart failure patients who also have IR for 4 months and examine the effects before and after 4 months of treatment. It is a double blind control study, therefore, neither the examiner nor the patient know which drug they receive (either active drug- Metformin, or a placebo).
The main objective is to assess their exercise capacity using an exercise test called Innocor System. It is a bicycle based exercise test that involves patient breathing into a mouth piece before and during exercise in order for the machine to work out the maximum oxygen consumption and pumping power of the heart.
The other objectives of the trial are looking at the possible mechanisms of improving exercise capacity. We aim to answer the following questions by doing the following tests:
Does exercise capacity improve because of
- The effect of metformin on the heart? We will answer this question by doing an ultrasound scan of the heart (Echocardiography)
- The effects on the blood vessels? We plan to perform a test called flow-mediated dilatation, it is an ultrasound scan of the artery in the arm and also assess the blood flow in the skin using a test called Laser Doppler scan (small amount of medication will be delivered through a small electric current and the blood vessels response will be assessed using the laser doppler scan)
- The effects on the muscle? We will do a muscle biopsy looking at the enzymes activities in the muscle before and after taking 4 months of medication.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: MetforminReceiving Metformin for 4 months |
| 2 | Placebo comparator | Drug: Matched Placebo (Capsules)Matched Placebo for 4 months |
Who may qualify
- Ages
- 25 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients aged 25-80 yrs with compensated CHF in NYHA functional I-III with evidence of insulin resistance [fasting insulin resistance index values of > 2.7 are said to have insulin resistance].
- Documented Left ventricular systolic dysfunction or LV ejection fraction < 35%
Key exclusion criteria (6 listed)
- Elderly patients (aged >80 yrs);
- Patients with decompensated CHF (NYHA functional class IV and /or signs of decompensated CHF);
- Renal dysfunction (serum creatinine > 160 mmol/L);
- Patients who are unable to exercise including patients that will be excluded for reasons of safety or potential effects on exercise performance. Therefore, patients with angina or other cardiac or pulmonary symptoms potentially limiting exercise performance will be excluded.
- Systolic blood pressure >190 mmHg at rest or >250 mmHg with exercise or diastolic blood pressure >95 mmHg at rest or >105 mmHg with exercise will also be a reason for exclusion;
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 |
|---|---|---|
| MetforminStarted at 500mg bd for 2 weeks. If well tolerated, increase to 1000mg bd for 14 weeks | Drug | 1 |
| Matched Placebo (Capsules)Similar dosing regime as active comparator | Drug | 2 |
Primary outcome
Peak VO2
Time frame: 4 months
Peak VO2 after 4 months of intervention with either metformin or placebo. The Mean difference between baseline and after 4 months was analyzed using t-test comparing metformin and placebo.
1 secondary outcome
Possible Mechanisms That Can Explain the Improvement of Exercise Capacity
Time frame: 4 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38696701Schiavone M, Gasperetti A, Vogler J, Compagnucci P, Laredo M, Breitenstein A, Gulletta S, Martinek M, Kaiser L, Tundo F, Palmisano P, Rovaris G, Curnis A, Kuschyk J, Biffi M, Tilz R, Di Biase L, Tondo C, Forleo GB; i-SUSI investigators. Sex differences among subcutaneous implantable cardioverter-defibrillator recipients: a propensity-matched, multicentre, international analysis from the i-SUSI project. Europace. 2024 May 2;26(5):euae115. doi: 10.1093/europace/euae115.
- Derived from this study: PubMed 38584394Schiavone M, Gasperetti A, Compagnucci P, Vogler J, Laredo M, Montemerlo E, Gulletta S, Breitenstein A, Ziacchi M, Martinek M, Casella M, Palmisano P, Kaiser L, Lavalle C, Calo L, Seidl S, Saguner AM, Rovaris G, Kuschyk J, Biffi M, Di Biase L, Dello Russo A, Tondo C, Della Bella P, Tilz R, Forleo GB; iSUSI investigators. Impact of ventricular tachycardia ablation in subcutaneous implantable cardioverter defibrillator carriers: a multicentre, international analysis from the iSUSI project. Europace. 2024 Mar 30;26(4):euae066. doi: 10.1093/europace/euae066.
- Derived from this study: PubMed 34271173Gasperetti A, Schiavone M, Ziacchi M, Vogler J, Breitenstein A, Laredo M, Palmisano P, Ricciardi D, Mitacchione G, Compagnucci P, Bisignani A, Angeletti A, Casella M, Picarelli F, Fink T, Kaiser L, Hakmi S, Calo L, Pignalberi C, Santini L, Lavalle C, Pisano E, Olivotto I, Tondo C, Curnis A, Dello Russo A, Badenco N, Steffel J, Love CJ, Tilz R, Forleo G, Biffi M. Long-term complications in patients implanted with subcutaneous implantable cardioverter-defibrillators: Real-world data from the extended ELISIR experience. Heart Rhythm. 2021 Dec;18(12):2050-2058. doi: 10.1016/j.hrthm.2021.07.008. Epub 2021 Jul 14.
- Derived from this study: PubMed 27418629Cameron AR, Morrison VL, Levin D, Mohan M, Forteath C, Beall C, McNeilly AD, Balfour DJ, Savinko T, Wong AK, Viollet B, Sakamoto K, Fagerholm SC, Foretz M, Lang CC, Rena G. Anti-Inflammatory Effects of Metformin Irrespective of Diabetes Status. Circ Res. 2016 Aug 19;119(5):652-65. doi: 10.1161/CIRCRESAHA.116.308445. Epub 2016 Jul 14.
- Derived from this study: PubMed 22740509Wong AK, Symon R, AlZadjali MA, Ang DS, Ogston S, Choy A, Petrie JR, Struthers AD, Lang CC. The effect of metformin on insulin resistance and exercise parameters in patients with heart failure. Eur J Heart Fail. 2012 Nov;14(11):1303-10. doi: 10.1093/eurjhf/hfs106. Epub 2012 Jun 27.
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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.
Chim Lang, MD, FRCP principal investigator
University of Dundee, Scotland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Metformin in people with Congestive Heart Failure and Insulin Resistance, run by University of Dundee at 1 site in United Kingdom.
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 2 inclusion and 6 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: finished, as of the sponsor's last update on 6 Jun 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 United Kingdom. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Jun 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Peak VO2 (time frame: 4 months). 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 NCT00473876, which also lists 5 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 6 Jun 2013.