Ischemia-Reperfusion InjuryPhase 2NCT00405015
The Effect of Rosiglitazone on Ischemia-reperfusion-injury Using Annexin A5 Scintigraphy.
A Phase 2 study testing rosiglitazone in people with Ischemia-Reperfusion Injury and The Metabolic Syndrome, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
Cardiovascular disease is the leading cause of death in diabetic patients due to both a high event rate and a worse outcome. A pharmacological intervention that reduces ischemia-reperfusion-injury would improve the outcome of diabetic patients after a cardiovascular event. Read more about this study
- Who is it for?
- Ages 20 to 70 years
- Conditions the study is for
- Ischemia-Reperfusion Injury, The Metabolic Syndrome
- What is being tested?
- rosiglitazone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteNetherlands
- Study dates
- Apr 2007to Oct 2008
- Phase
- Phase 2
- 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 20 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- At least 3 features of the metabolic syndrome (AHA/NHLBI).
- Willing and able to provide a signed and dated written informed consent.
- Men or postmenopausal women aged between 20 and 70 years.
Who cannot join
- Fasting glucose > 7,0 mmol/L or the use of hypoglycaemic agents. If fasting plasma glucose is between 6.1 and 7,0 mmol/L, an oral 75 g glucose test will be performed to exclude diabetes mellitus.
- Exposure to a PPAR-g agonist during the last 4 months or a documented significant hypersensitivity to a PPAR-g agonist.
- Participant in another study.
- Angina or heart failure (NYHA I-IV).
- Clinically significant liver disease (3 times the upper normal limit of ALAT, ASAT, AF, γGT or LDH)
- Clinically significant anemia (male Hb < 6,9 mmol/L, female < 6,25 mmol/L)
Show all 10Show fewer
- Creatinin clearance < 40 mL/min
- Alcohol or drug abuse.
- Any physical inability to perform the exercise protocol.
- Administration of any radio pharmacon for research purposes in the previous 5 years.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effect of Rosiglitazone on Ischemia-reperfusion-injury Using Annexin A5 Scintigraphy. A Double Blind Placebo- Controlled Cross-over Study in Subjects With the Metabolic Syndrome
Cardiovascular disease is the leading cause of death in diabetic patients due to both a high event rate and a worse outcome. A pharmacological intervention that reduces ischemia-reperfusion-injury would improve the outcome of diabetic patients after a cardiovascular event. In the present study, we will use annexinA5 scintigraphy to address the following hypothesis:
Rosiglitazone reduces ischemia-reperfusion-injury in humans with insulin resistance.
Read the detailed description
Rationale: Cardiovascular disease is the leading cause of death in diabetic patients due to both a high event rate and a worse outcome. A pharmacological intervention that reduces ischemia-reperfusion-injury would improve the outcome of diabetic patients after a cardiovascular event. The thiazolidinedione derivatives are peroxisome proliferator-activated receptor-γ (PPARγ) ligands that are approved for the treatment of hyperglycemia in type 2 diabetes mellitus. Animal data suggest that PPARγ ligands can protect against ischemia-reperfusion-injury by improving insulin responsiveness. However, no human data on these beneficial effects are available. Recently, our group developed a human in vivo model to quantify ischemia-reperfusion-injury. In this model annexin A5 scintigraphy is used to visualize early and reversible cellular membrane changes that occur in the forearm skeletal muscle vascular bed after ischemic exercise. In the present study, we will use this approach to address the following hypothesis: Rosiglitazone reduces ischemia-reperfusion-injury in humans with insulin resistance, selected by using the criteria for the metabolic syndrome.
Study design: This is a single-center randomized, double blind, placebo-controlled crossover study with a washout period of 6 weeks.
Study population: Men and postmenopausal women, age 20-70 years with the metabolic syndrome.
Intervention: Every subject uses during 8 weeks rosiglitazone 4 mg bd and placebo bd. Week 8 and 22: assessment of ischemic-reperfusion injury with Technetium Annexin A5 Scintigraphy. Ischemic intervention: 10 minutes ischemia of the non-dominant arm with at the same time rhythmic contractions of the forearm and hand muscles.
Main study parameters/endpoints: Annexin targeting in the thenar muscle after ischemic exercise. The primary analysis is the difference in annexin targeting following 8 weeks of treatment with rosiglitazone 4 mg bd or placebo.
- Being tested
- rosiglitazone
- Keywords
- rosiglitazone, ischemia-reperfusion injury, human, Annexin A5 scintigraphy, metabolic syndrome
- Medical subject headings
- Reperfusion Injury, Metabolic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rosiglitazoneDrug
Rosiglitazone 4 mg bidaily for 8 weeks
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Placebo first Receives: Drug: rosiglitazone |
| 2 | Experimental | Rosiglitazone first Receives: Drug: rosiglitazone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Annexin targeting in the thenar muscle after ischemic exercise. The primary analysis is the difference in annexin targeting following 8 weeks of treatment with rosiglitazone 4 mg bd or placebo.
Secondary outcomes (2)
The effect of rosiglitazone as compared to placebo on the HOMA-index.
Changes in vital signs, body weight, clinical laboratory parameters and adverse events monitoring during the study.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2006 (estimated)
- Study startApr 2007
- Primary completionJul 2008
- Study completionOct 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Ischemia-Reperfusion InjuryStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline
- Investigators
- Gerard A Rongen, MD, PhD, Principal investigator, Radboud University Nijmegen Medical Center, department pharmacology-ToxicologyAlexander JM Rennings, MD, Principal investigator, Radboud University Nijmegen Medical Center, department of pharmacology-ToxicologyPaul Smits, MD, PhD, Study director, Radboud University Nijmegen Medical Center, head of department of Parmacology-Toxicology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00405015
- Sponsor's protocol ID
- AR49653-4
- Other IDs
- EudraCT number 2006-006208-13
- Status last verified
- Oct 2008
- First submitted
- 28 Nov 2006
- Last updated
- 24 Aug 2010
- Results posted
- No
- Data monitoring committee
- No
Publications
Grundy SM, Benjamin IJ, Burke GL, Chait A, Eckel RH, Howard BV, Mitch W, Smith SC Jr, Sowers JR. Diabetes and cardiovascular disease: a statement for healthcare professionals from the American Heart Association. Circulation. 1999 Sep 7;100(10):1134-46. doi: 10.1161/01.cir.100.10.1134. No abstract available.
PubMed 10477542Aronson D, Rayfield EJ, Chesebro JH. Mechanisms determining course and outcome of diabetic patients who have had acute myocardial infarction. Ann Intern Med. 1997 Feb 15;126(4):296-306. doi: 10.7326/0003-4819-126-4-199702150-00006.
PubMed 9036802Yue TL, Bao W, Gu JL, Cui J, Tao L, Ma XL, Ohlstein EH, Jucker BM. Rosiglitazone treatment in Zucker diabetic Fatty rats is associated with ameliorated cardiac insulin resistance and protection from ischemia/reperfusion-induced myocardial injury. Diabetes. 2005 Feb;54(2):554-62. doi: 10.2337/diabetes.54.2.554.
PubMed 15677515Rongen GA, Oyen WJ, Ramakers BP, Riksen NP, Boerman OC, Steinmetz N, Smits P. Annexin A5 scintigraphy of forearm as a novel in vivo model of skeletal muscle preconditioning in humans. Circulation. 2005 Jan 18;111(2):173-8. doi: 10.1161/01.CIR.0000151612.02223.F2. Epub 2004 Dec 27.
PubMed 15623546
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Rosiglitazone on Ischemia-reperfusion-injury Using Annexin A5 Scintigraphy. A Double Blind Placebo- Controlled Cross-over Study in Subjects With the Metabolic Syndrome
- ClinicalTrials.gov ID
- NCT00405015
- Acronym / sponsor ID
- AR49653-4
- Keywords
- rosiglitazone, ischemia-reperfusion injury, human, Annexin A5 scintigraphy, metabolic syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- GlaxoSmithKline
- Study start
- Apr 2007
- Primary completion
- Jul 2008 (actual)
- Study completion
- Oct 2008 (actual)
- First posted
- 29 Nov 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.
Cardiovascular disease is the leading cause of death in diabetic patients due to both a high event rate and a worse outcome. A pharmacological intervention that reduces ischemia-reperfusion-injury would improve the outcome of diabetic patients after a cardiovascular event. In the present study, we will use annexinA5 scintigraphy to address the following hypothesis:
Rosiglitazone reduces ischemia-reperfusion-injury in humans with insulin resistance.
Detailed description
Rationale: Cardiovascular disease is the leading cause of death in diabetic patients due to both a high event rate and a worse outcome. A pharmacological intervention that reduces ischemia-reperfusion-injury would improve the outcome of diabetic patients after a cardiovascular event. The thiazolidinedione derivatives are peroxisome proliferator-activated receptor-γ (PPARγ) ligands that are approved for the treatment of hyperglycemia in type 2 diabetes mellitus. Animal data suggest that PPARγ ligands can protect against ischemia-reperfusion-injury by improving insulin responsiveness. However, no human data on these beneficial effects are available. Recently, our group developed a human in vivo model to quantify ischemia-reperfusion-injury. In this model annexin A5 scintigraphy is used to visualize early and reversible cellular membrane changes that occur in the forearm skeletal muscle vascular bed after ischemic exercise. In the present study, we will use this approach to address the following hypothesis: Rosiglitazone reduces ischemia-reperfusion-injury in humans with insulin resistance, selected by using the criteria for the metabolic syndrome.
Study design: This is a single-center randomized, double blind, placebo-controlled crossover study with a washout period of 6 weeks.
Study population: Men and postmenopausal women, age 20-70 years with the metabolic syndrome.
Intervention: Every subject uses during 8 weeks rosiglitazone 4 mg bd and placebo bd. Week 8 and 22: assessment of ischemic-reperfusion injury with Technetium Annexin A5 Scintigraphy. Ischemic intervention: 10 minutes ischemia of the non-dominant arm with at the same time rhythmic contractions of the forearm and hand muscles.
Main study parameters/endpoints: Annexin targeting in the thenar muscle after ischemic exercise. The primary analysis is the difference in annexin targeting following 8 weeks of treatment with rosiglitazone 4 mg bd or placebo.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: rosiglitazonePlacebo first |
| 2 | Experimental | Drug: rosiglitazoneRosiglitazone first |
Who may qualify
- Ages
- 20 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- At least 3 features of the metabolic syndrome (AHA/NHLBI).
- Willing and able to provide a signed and dated written informed consent.
- Men or postmenopausal women aged between 20 and 70 years.
Key exclusion criteria (10 listed)
- Fasting glucose > 7,0 mmol/L or the use of hypoglycaemic agents. If fasting plasma glucose is between 6.1 and 7,0 mmol/L, an oral 75 g glucose test will be performed to exclude diabetes mellitus.
- Exposure to a PPAR-g agonist during the last 4 months or a documented significant hypersensitivity to a PPAR-g agonist.
- Participant in another study.
- Angina or heart failure (NYHA I-IV).
- Clinically significant liver disease (3 times the upper normal limit of ALAT, ASAT, AF, γGT or LDH)
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 |
|---|---|---|
| rosiglitazoneRosiglitazone 4 mg bidaily for 8 weeks | Drug | 1, 2 |
Primary outcome
Annexin targeting in the thenar muscle after ischemic exercise. The primary analysis is the difference in annexin targeting following 8 weeks of treatment with rosiglitazone 4 mg bd or placebo.
2 secondary outcomes
The effect of rosiglitazone as compared to placebo on the HOMA-index.
Changes in vital signs, body weight, clinical laboratory parameters and adverse events monitoring during the study.
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 24 Aug 2010.
- Background: PubMed 10477542Grundy SM, Benjamin IJ, Burke GL, Chait A, Eckel RH, Howard BV, Mitch W, Smith SC Jr, Sowers JR. Diabetes and cardiovascular disease: a statement for healthcare professionals from the American Heart Association. Circulation. 1999 Sep 7;100(10):1134-46. doi: 10.1161/01.cir.100.10.1134. No abstract available.
- Background: PubMed 9036802Aronson D, Rayfield EJ, Chesebro JH. Mechanisms determining course and outcome of diabetic patients who have had acute myocardial infarction. Ann Intern Med. 1997 Feb 15;126(4):296-306. doi: 10.7326/0003-4819-126-4-199702150-00006.
- Background: PubMed 15677515Yue TL, Bao W, Gu JL, Cui J, Tao L, Ma XL, Ohlstein EH, Jucker BM. Rosiglitazone treatment in Zucker diabetic Fatty rats is associated with ameliorated cardiac insulin resistance and protection from ischemia/reperfusion-induced myocardial injury. Diabetes. 2005 Feb;54(2):554-62. doi: 10.2337/diabetes.54.2.554.
- Background: PubMed 15623546Rongen GA, Oyen WJ, Ramakers BP, Riksen NP, Boerman OC, Steinmetz N, Smits P. Annexin A5 scintigraphy of forearm as a novel in vivo model of skeletal muscle preconditioning in humans. Circulation. 2005 Jan 18;111(2):173-8. doi: 10.1161/01.CIR.0000151612.02223.F2. Epub 2004 Dec 27.
Related trials for Ischemia-Reperfusion Injury
Not yet recruiting
New Biomarkers for Organ Viability Assessment During Hypothermic Machine Perfusion in Liver Transplantation: the Role of Extemporaneous Histological Examination.
Liver Transplantation (LT), Early Allograft Dysfunction
Active, not recruitingPhase 3
The Danish Out-of-Hospital Cardiac Arrest Study
Out-Of-Hospital Cardiac Arrest, Post-Cardiac Arrest Syndrome
RecruitingPhase 2
Prevention of Reperfusion Injury Outcomes Through Effective Cardioprotection Targeting Myocardial Infarction
Myocardial Infarction, Reperfusion Injury
Recruiting
Rapid Local Ischemic Postconditioning on Stroke After Thrombectomy
Acute Ischemic Stroke
Recruiting
Avoiding Recooling After Normothermic Machine Perfusion in Liver Transplantation
Liver Transplantation (LT), Ischemia-Reperfusion Injury
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.
Gerard A Rongen, MD, PhD principal investigator
Radboud University Nijmegen Medical Center, department pharmacology-Toxicology
Alexander JM Rennings, MD principal investigator
Radboud University Nijmegen Medical Center, department of pharmacology-Toxicology
Paul Smits, MD, PhD study director
Radboud University Nijmegen Medical Center, head of department of Parmacology-Toxicology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing rosiglitazone in people with Ischemia-Reperfusion Injury and The Metabolic Syndrome, 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 3 inclusion and 10 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 24 Aug 2010. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Annexin targeting in the thenar muscle after ischemic exercise. The primary analysis is the difference in annexin targeting following 8 weeks of treatment with rosiglitazone 4 mg bd or placebo.. 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 NCT00405015, which also lists 4 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 24 Aug 2010.