Ischemia Reperfusion InjuryPhase 4MetFMDNCT01610401
The Metformin-FMD Trial
A Phase 4 study testing Metformin, Pretreatment with metformin in combination of infusion of caffeine. and No pretreatment with metformin in combination with infusion of caffeine in people with Ischemia Reperfusion Injury and Endothelial Function, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
In acute myocardial infarction early restoration of coronary blood flow is the most effective strategy to limit infarct-size. Paradoxically, reperfusion itself also aggravates myocardial injury and contributes to final infarct size, a process termed 'reperfusion injury'. Read more about this study
- Who is it for?
- Ages 30 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Ischemia Reperfusion Injury, Endothelial Function
- What is being tested?
- Metformin, Pretreatment with metformin in combination of infusion of caffeine. and No pretreatment with metformin in combination with infusion of caffeine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteNetherlands
- Study dates
- May 2012to Jan 2013
- Phase
- Phase 4
- 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 30 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age 30-50 years
- Written informed consent
Who cannot join
- Smoking
- Hypertension (in supine position: systolic BP > 140 mmHg, diastolic BP > 90 mmHg)
- Hyperlipidaemia (fasting total cholesterol > 5.5 mmol/L or random > 6.5 mmol/L)
- Diabetes Mellitus (fasting glucose > 7.0 mmol/L or random glucose > 11.0 mmol/L)
- History of any cardiovascular disease
- Concomitant use of medication
- Renal dysfunction (MDRD < 60 ml/min)
- Professional athletes
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Radboud University Nijmegen Medical Centre
Nijmegen, Gelderland, 6500 HB
About this study
Official title: Can Metformin Prevent Endothelial Ischemia and Reperfusion Injury? The Metformin-FMD Trial
In acute myocardial infarction early restoration of coronary blood flow is the most effective strategy to limit infarct-size. Paradoxically, reperfusion itself also aggravates myocardial injury and contributes to final infarct size, a process termed 'reperfusion injury'. Ischemia and reperfusion (IR)-induced endothelial dysfunction seems to play a pivotal role in this process, resulting in vasoconstriction and reduced blood flow to the already ischemic tissue. Recently, it has been shown that the glucose-lowering drug metformin is able to limit IR-injury in murine models of myocardial infarction, probably by increased formation of the endogenous nucleoside adenosine. In the current research proposal, the investigators aim to translate this finding to the human in vivo situation, using flow-mediated dilation (FMD) of the brachial artery as a well-validated model of (endothelial) IR-injury.
- Conditions
- Ischemia Reperfusion Injury, Endothelial Function
- Being tested
- Metformin, Pretreatment with metformin in combination of infusion of caffeine., No pretreatment with metformin in combination with infusion of caffeine
- Medical subject headings
- Reperfusion Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
metformin 500 mg three times a day, for 3 days
Pretreatment with metformin in combination of infusion of caffeine.Drug
Pretreatment with metformin 500 mg three times a day for 3 days, in combination with pretreatment with caffeine (4 mg/kg intravenously over 10 minutes) prior to FMD measurement
No pretreatment with metformin in combination with infusion of caffeineDrug
No pretreatment with metformin in combination with pretreatment with caffeine (4 mg/kg intravenously over 10 minutes).
| Study group | Role | What they receive |
|---|---|---|
| Pretreatment with metformin | Active comparator | Pretreatment with metformin 500 mg three times a day for 3 days. Receives: Drug: Metformin |
| No pretreatment. | No intervention | no intervention |
| Pretreatment with Metformin/caffeine | Active comparator | to study whether caffeine (4 mg/kg intravenously over 10 minutes) attenuates the protective effect of metformin (500 mg three times a day for 3 days) on FMD after ischemia/reperfusion Receives: Drug: Pretreatment with metformin in combination of infusion of caffeine. |
| No metformin, only pretreatment with caffeine | Other | No pretreatment with metformin, FMD measurement after forearm ischemia/reperfusion and infusion of caffeine (4 mg/kg intravenously over 10 minutes). Receives: Drug: No pretreatment with metformin in combination with infusion of caffeine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Metformin-FMD trial: The effect of pretreatment with metformin on FMD of the brachial artery after forearm ischemia and reperfusion.
Metformin-FMD trial: To study the effect of oral pretreatment with metformin (500 mg three times ad ay for 3 days) on flow mediated dilation of the brachial artery after 20 minutes of forearm ischemia and 20 minutes of reperfusion in healthy volunteers.
Measured: approx. 6 months
Control trial: the effect of caffeine on the protective effect of metformin on FMD after ischemia and reperfusion.
Control trial: when metformin displays a protective effect on endothelial function, we will conduct a second experiment to study whether caffeine, an adenosine receptor antagonist, attenuates the protective effect of metformin on flow mediated dilation after 20 minutes of ischemia and 20 minutes of reperfusion in healthy volunteers.
Measured: approx. 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2012 (estimated)
- Study startMay 2012
- Primary completionJan 2013
- Study completionJan 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ischemia Reperfusion InjuryStudies 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
- Crossover
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- N. Riksen, MD, PhD, Principal investigator, Radboud University Medical CenterG.A. Rongen, M.D., Principal investigator, Radboud University Medical CenterD.H. Thijssen, PhD, Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01610401
- Sponsor's protocol ID
- Metformin-FMD 001
- Acronym
- MetFMD
- Status last verified
- Feb 2012
- First submitted
- 25 May 2012
- Last updated
- 20 May 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
El Messaoudi S, Schreuder TH, Kengen RD, Rongen GA, van den Broek PH, Thijssen DH, Riksen NP. Impact of metformin on endothelial ischemia-reperfusion injury in humans in vivo: a prospective randomized open, blinded-endpoint study. PLoS One. 2014 Apr 22;9(4):e96062. doi: 10.1371/journal.pone.0096062. eCollection 2014.
PubMed 24755906
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Can Metformin Prevent Endothelial Ischemia and Reperfusion Injury? The Metformin-FMD Trial
- ClinicalTrials.gov ID
- NCT01610401
- Acronym / sponsor ID
- MetFMD / Metformin-FMD 001
- Conditions
- Ischemia Reperfusion Injury, Endothelial Function
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- May 2012
- Primary completion
- Jan 2013 (actual)
- Study completion
- Jan 2013 (actual)
- First posted
- 4 Jun 2012 (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.
In acute myocardial infarction early restoration of coronary blood flow is the most effective strategy to limit infarct-size. Paradoxically, reperfusion itself also aggravates myocardial injury and contributes to final infarct size, a process termed 'reperfusion injury'. Ischemia and reperfusion (IR)-induced endothelial dysfunction seems to play a pivotal role in this process, resulting in vasoconstriction and reduced blood flow to the already ischemic tissue. Recently, it has been shown that the glucose-lowering drug metformin is able to limit IR-injury in murine models of myocardial infarction, probably by increased formation of the endogenous nucleoside adenosine. In the current research proposal, the investigators aim to translate this finding to the human in vivo situation, using flow-mediated dilation (FMD) of the brachial artery as a well-validated model of (endothelial) IR-injury.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Pretreatment with metformin | Active comparator | Drug: MetforminPretreatment with metformin 500 mg three times a day for 3 days. |
| No pretreatment. | No intervention | –no intervention |
| Pretreatment with Metformin/caffeine | Active comparator | Drug: Pretreatment with metformin in combination of infusion of caffeine.to study whether caffeine (4 mg/kg intravenously over 10 minutes) attenuates the protective effect of metformin (500 mg three times a day for 3 days) on FMD after ischemia/reperfusion |
| No metformin, only pretreatment with caffeine | Other | Drug: No pretreatment with metformin in combination with infusion of caffeineNo pretreatment with metformin, FMD measurement after forearm ischemia/reperfusion and infusion of caffeine (4 mg/kg intravenously over 10 minutes). |
Who may qualify
- Ages
- 30 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Age 30-50 years
- Written informed consent
Key exclusion criteria (8 listed)
- Smoking
- Hypertension (in supine position: systolic BP > 140 mmHg, diastolic BP > 90 mmHg)
- Hyperlipidaemia (fasting total cholesterol > 5.5 mmol/L or random > 6.5 mmol/L)
- Diabetes Mellitus (fasting glucose > 7.0 mmol/L or random glucose > 11.0 mmol/L)
- History of any cardiovascular disease
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 |
|---|---|---|
| Metforminmetformin 500 mg three times a day, for 3 days | Drug | Pretreatment with metformin |
| Pretreatment with metformin in combination of infusion of caffeine.Pretreatment with metformin 500 mg three times a day for 3 days, in combination with pretreatment with caffeine (4 mg/kg intravenously over 10 minutes) prior to FMD measurement | Drug | Pretreatment with Metformin/caffeine |
| No pretreatment with metformin in combination with infusion of caffeineNo pretreatment with metformin in combination with pretreatment with caffeine (4 mg/kg intravenously over 10 minutes). | Drug | No metformin, only pretreatment with caffeine |
Primary outcome
Metformin-FMD trial: The effect of pretreatment with metformin on FMD of the brachial artery after forearm ischemia and reperfusion.
Time frame: approx. 6 months
Metformin-FMD trial: To study the effect of oral pretreatment with metformin (500 mg three times ad ay for 3 days) on flow mediated dilation of the brachial artery after 20 minutes of forearm ischemia and 20 minutes of reperfusion in healthy volunteers.
Control trial: the effect of caffeine on the protective effect of metformin on FMD after ischemia and reperfusion.
Time frame: approx. 6 months
Control trial: when metformin displays a protective effect on endothelial function, we will conduct a second experiment to study whether caffeine, an adenosine receptor antagonist, attenuates the protective effect of metformin on flow mediated dilation after 20 minutes of ischemia and 20 minutes of reperfusion in healthy volunteers.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2013.
- Derived from this study: PubMed 24755906El Messaoudi S, Schreuder TH, Kengen RD, Rongen GA, van den Broek PH, Thijssen DH, Riksen NP. Impact of metformin on endothelial ischemia-reperfusion injury in humans in vivo: a prospective randomized open, blinded-endpoint study. PLoS One. 2014 Apr 22;9(4):e96062. doi: 10.1371/journal.pone.0096062. eCollection 2014.
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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.
N. Riksen, MD, PhD principal investigator
Radboud University Medical Center
G.A. Rongen, M.D. principal investigator
Radboud University Medical Center
D.H. Thijssen, PhD principal investigator
Radboud University Medical Center
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, Pretreatment with metformin in combination of infusion of caffeine. and No pretreatment with metformin in combination with infusion of caffeine in people with Ischemia Reperfusion Injury and Endothelial Function, run by Radboud University Medical Center at 1 site in Netherlands.
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 8 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 20 May 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 Netherlands. 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. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Metformin-FMD trial: The effect of pretreatment with metformin on FMD of the brachial artery after forearm ischemia and reperfusion. (time frame: approx. 6 months). The study lists 2 primary outcomes in all. 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 NCT01610401, which also lists 1 linked publication.
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 20 May 2013.