Coronary Artery DiseasePhase 1NCT02009527
Arginase Inhibition in Ischemia-reperfusion Injury
A Phase 1 study testing N-hydroxy-nor-arginine and NaCl in people with Coronary Artery Disease and Type 2 Diabetes Mellitus, run by Karolinska Institutet at 1 site in Sweden.
Trial summary
The present project is designed to test the hypothesis that arginase contributes to endothelial dysfunction induced by ischemia-reperfusion in patients with coronary artery disease. Read more about this study
- Who is it for?
- Ages Up to 80 years, men only
- Conditions the study is for
- Coronary Artery Disease, Type 2 Diabetes Mellitus
- What is being tested?
- N-hydroxy-nor-arginine and NaCl
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteSweden
- Study dates
- Jan 2012to Sep 2013
- Phase
- Phase 1
- 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 Up to 80 years
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Coronary artery disease
Who cannot join
- Age >80 years, Myocardial infarction/unstable angina within 6 weeks prior to the study, Raynaud's phenomenon, peripheral vasculopathies, arterial shunting or other vascular surgery of the study arm, Any concomitant disease or condition that may interfere with the possibility for the patient to comply with or complete the study protocol, Participant in an ongoing study, Unwillingness to participate following oral and written information.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Arginase Inhibition on Endothelial Function Induced by Ischemia-reperfusion in Patients With Coronary Artery Disease
The present project is designed to test the hypothesis that arginase contributes to endothelial dysfunction induced by ischemia-reperfusion in patients with coronary artery disease.
Read the detailed description
Background: Arginase competes with nitric oxide synthase for their common substrate L-arginine. Up-regulation of arginase in coronary artery disease (CAD) and diabetes mellitus may reduce nitric oxide bioavailability contributing to endothelial dysfunction and ischemia-reperfusion injury. Arginase inhibition reduces infarct size in animal models. Therefore the aim of the current study was to investigate if arginase inhibition protects from endothelial dysfunction induced by ischemia-reperfusion in patients with CAD with or without type 2 diabetes.
Methods: Male patients with CAD (n=12) or CAD + type 2 diabetes (n=12), were included in this cross-over study with blinded evaluation. Endothelium-dependent vasodilatation was assessed by flow-mediated dilatation (FMD) of the radial artery before and after 20 min ischemia-reperfusion during intra-arterial infusion of the arginase inhibitor (N-hydroxy-nor-L-arginine, 0.1 mg/min) or saline.
Results: The forearm ischemia-reperfusion was well tolerated. Endothelium-independent vasodilatation was assessed by sublingual nitroglycerin. Ischemia-reperfusion decreased FMD in patients with CAD from 12.7±5.2% to 7.9±4.0% during saline administration (P<0.05). N-hydroxy-nor-L-arginine administration prevented the decrease in FMD in the CAD group (10.3±4.3% at baseline vs. 11.5±3.6% at reperfusion). Ischemia-reperfusion did not significantly reduce FMD in patients with CAD + type 2 diabetes. However, FMD at reperfusion was higher following nor-NOHA than following saline administration in both groups (P<0.01). Endothelium-independent vasodilatation did not differ between the occasions.
Conclusions: Inhibition of arginase protects against endothelial dysfunction caused by ischemia-reperfusion in patients with CAD. Arginase inhibition may thereby be a promising therapeutic strategy in the treatment of ischemia-reperfusion injury.
- Conditions
- Coronary Artery Disease, Type 2 Diabetes Mellitus
- Being tested
- N-hydroxy-nor-arginine, NaCl
- Medical subject headings
- Coronary Artery Disease, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-hydroxy-nor-arginineDrug
NaClDrug
| Study group | Role | What they receive |
|---|---|---|
| N-hydroxy-nor-arginine | Experimental | N-hydroxy-nor-arginine 0.1 mg/ min i.a. for 20 min Receives: Drug: N-hydroxy-nor-arginine |
| NaCl | Placebo comparator | NaCl 0.9%, 6 ml/min i.a. for 20 min Receives: Drug: NaCl |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in endothelial function
Flow-mediated dilatation of the radial artery
Measured: 20 min of reperfusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2013 (estimated)
- Study startJan 2012
- Primary completionApr 2013
- Study completionSep 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 Coronary Artery DiseaseStudies of the same condition, open and under way.
- More trials run by Karolinska InstitutetThe 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 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Karolinska Institutet
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, John Pernow, Karolinska Institutet
- Investigators
- John Pernow, MD, PhD, Principal investigator, Karolinska Institutet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02009527
- Sponsor's protocol ID
- AIR
- Status last verified
- Apr 2015
- First submitted
- 8 Dec 2013
- Last updated
- 20 Apr 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Kovamees O, Shemyakin A, Pernow J. Effect of arginase inhibition on ischemia-reperfusion injury in patients with coronary artery disease with and without diabetes mellitus. PLoS One. 2014 Jul 29;9(7):e103260. doi: 10.1371/journal.pone.0103260. eCollection 2014.
PubMed 25072937
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Arginase Inhibition on Endothelial Function Induced by Ischemia-reperfusion in Patients With Coronary Artery Disease
- ClinicalTrials.gov ID
- NCT02009527
- Acronym / sponsor ID
- AIR
- Conditions
- Coronary Artery Disease, Type 2 Diabetes Mellitus
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Karolinska InstitutetUniversity, hospital or other
- Study start
- Jan 2012
- Primary completion
- Apr 2013 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 12 Dec 2013 (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.
The present project is designed to test the hypothesis that arginase contributes to endothelial dysfunction induced by ischemia-reperfusion in patients with coronary artery disease.
Detailed description
Background: Arginase competes with nitric oxide synthase for their common substrate L-arginine. Up-regulation of arginase in coronary artery disease (CAD) and diabetes mellitus may reduce nitric oxide bioavailability contributing to endothelial dysfunction and ischemia-reperfusion injury. Arginase inhibition reduces infarct size in animal models. Therefore the aim of the current study was to investigate if arginase inhibition protects from endothelial dysfunction induced by ischemia-reperfusion in patients with CAD with or without type 2 diabetes.
Methods: Male patients with CAD (n=12) or CAD + type 2 diabetes (n=12), were included in this cross-over study with blinded evaluation. Endothelium-dependent vasodilatation was assessed by flow-mediated dilatation (FMD) of the radial artery before and after 20 min ischemia-reperfusion during intra-arterial infusion of the arginase inhibitor (N-hydroxy-nor-L-arginine, 0.1 mg/min) or saline.
Results: The forearm ischemia-reperfusion was well tolerated. Endothelium-independent vasodilatation was assessed by sublingual nitroglycerin. Ischemia-reperfusion decreased FMD in patients with CAD from 12.7±5.2% to 7.9±4.0% during saline administration (P<0.05). N-hydroxy-nor-L-arginine administration prevented the decrease in FMD in the CAD group (10.3±4.3% at baseline vs. 11.5±3.6% at reperfusion). Ischemia-reperfusion did not significantly reduce FMD in patients with CAD + type 2 diabetes. However, FMD at reperfusion was higher following nor-NOHA than following saline administration in both groups (P<0.01). Endothelium-independent vasodilatation did not differ between the occasions.
Conclusions: Inhibition of arginase protects against endothelial dysfunction caused by ischemia-reperfusion in patients with CAD. Arginase inhibition may thereby be a promising therapeutic strategy in the treatment of ischemia-reperfusion injury.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| N-hydroxy-nor-arginine | Experimental | Drug: N-hydroxy-nor-arginineN-hydroxy-nor-arginine 0.1 mg/ min i.a. for 20 min |
| NaCl | Placebo comparator | Drug: NaClNaCl 0.9%, 6 ml/min i.a. for 20 min |
Who may qualify
- Ages
- Up to 80 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- Coronary artery disease
Key exclusion criteria (1 listed)
- Age >80 years, Myocardial infarction/unstable angina within 6 weeks prior to the study, Raynaud's phenomenon, peripheral vasculopathies, arterial shunting or other vascular surgery of the study arm, Any concomitant disease or condition that may interfere with the possibility for the patient to comply with or complete the study protocol, Participant in an ongoing study, Unwillingness to participate following oral and written information.
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 |
|---|---|---|
| N-hydroxy-nor-arginine | Drug | N-hydroxy-nor-arginine |
| NaCl | Drug | NaCl |
Primary outcome
Change in endothelial function
Time frame: 20 min of reperfusion
Flow-mediated dilatation of the radial artery
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 Apr 2015.
- Derived from this study: PubMed 25072937Kovamees O, Shemyakin A, Pernow J. Effect of arginase inhibition on ischemia-reperfusion injury in patients with coronary artery disease with and without diabetes mellitus. PLoS One. 2014 Jul 29;9(7):e103260. doi: 10.1371/journal.pone.0103260. 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.
John Pernow, MD, PhD principal investigator
Karolinska Institutet
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing N-hydroxy-nor-arginine and NaCl in people with Coronary Artery Disease and Type 2 Diabetes Mellitus, run by Karolinska Institutet at 1 site in Sweden.
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 1 inclusion and 1 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 Apr 2015. 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 Sweden. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Change in endothelial function (time frame: 20 min of reperfusion). 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 NCT02009527, 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 Apr 2015.