The Effect of Ischaemic-Reperfusion and Remote Ischaemic Preconditioning in Man - A Bradykinin Dependent Pathway

This study has been completed.
Sponsor:
Collaborators:
University of Aarhus
University of Oxford
Information provided by:
University of Edinburgh
ClinicalTrials.gov Identifier:
NCT00965393
First received: August 19, 2009
Last updated: October 22, 2010
Last verified: October 2010
  Purpose

Heart attacks are usually caused by a blood clot blocking an artery supplying blood to the heart. Current treatments are designed at relieving this blockage as quickly as possible to minimize damage to the heart muscle. However in restoring the supply of blood local damage known as "ischaemia-reperfusion injury" may occur. The aim of this study is to assess how clot forming and clot dissolving pathways are affected during this process, and examine the role of a natural inflammatory hormone, bradykinin. This will help the investigators to understand the mechanism by which ischaemia-reperfusion injury may occur and to devise new treatments for heart attacks.


Condition Intervention
Ischaemic Heart Diseases
Procedure: Forearm vascular study
Drug: Placebo
Drug: bradykinin receptor antagonist (HOE-140)

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: The Effect of Ischaemic-Reperfusion and Remote Ischaemic Preconditioning in Man - A Bradykinin Dependent Pathway

Resource links provided by NLM:


Further study details as provided by University of Edinburgh:

Primary Outcome Measures:
  • Change in forearm blood flow in response to vasodilators (ACh(, ischaemia reperfusion and ischaemic preconditioning [ Time Frame: 20 fixed timepoints during each study visit (3hrs) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in platelet-monocyte-binding after ischaemia reperfusion and ischaemic preconditioning [ Time Frame: 4 fixed timepoints during each study visit (3hrs) ] [ Designated as safety issue: No ]

Estimated Enrollment: 12
Study Start Date: August 2009
Study Completion Date: October 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 1
Prior to 20 mins of ischaemia induced by a blood pressure cuff inflated to 200 mmHg around the upper non-dominant arm, remote ischaemic preconditioning will be induced by inflating a cuff around the dominant arm to 200 mmHg for 5 mins followed by 5 mins of reperfusion. This cycle will be repeated 3 times. Systemic infusion of placebo (saline).
Procedure: Forearm vascular study
Forearm blood flow measured by venous occlusion plethysmography during interarterial infusion of vasodilators (Ach). Venous blood sampling via cannula in antecubital fossa.
Drug: Placebo
Systemic infusion of placebo (saline)
Active Comparator: 2
Prior to 20 mins of ischaemia induced by a blood pressure cuff inflated to 200 mmHg around the upper non-dominant arm, remote ischaemic preconditioning will be induced by inflating a cuff around the dominant arm to 200 mmHg for 5 mins followed by 5 mins of reperfusion. This cycle will be repeated 3 times. Systemic infusion of bradykinin receptor antagonist (HOE-140).
Procedure: Forearm vascular study
Forearm blood flow measured by venous occlusion plethysmography during interarterial infusion of vasodilators (Ach). Venous blood sampling via cannula in antecubital fossa.
Drug: bradykinin receptor antagonist (HOE-140)
Systemic infusion of bradykinin receptor antagonist (HOE-140)

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy males between 18-65 years of ages.
  • Non-smokers.

Exclusion Criteria:

  • Any concurrent illness or chronic medical condition.
  • Concurrent use of vasoactive medication.
  • Smoking history.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00965393

Locations
United Kingdom
University of Edinburgh, 49 Little France Crescent
Edinburgh, United Kingdom, EH16 4SB
Sponsors and Collaborators
University of Edinburgh
University of Aarhus
University of Oxford
Investigators
Study Director: David E Newby, PhD, FRCP University of Edinburgh
Study Director: Rajesh K Kharbanda, PhD, FRCP University of Oxford
  More Information

No publications provided

Responsible Party: Christian M Pedersen, clinical research fellow, University of Edinburgh
ClinicalTrials.gov Identifier: NCT00965393     History of Changes
Other Study ID Numbers: CMP 5
Study First Received: August 19, 2009
Last Updated: October 22, 2010
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by University of Edinburgh:
Ischaemia reperfusion
Platelet activation
Endothelial function
Remote ischaemic preconditioning
Bradykinin

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Heart Diseases
Ischemia
Coronary Disease
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Pathologic Processes
Bradykinin
Kininogens
Icatibant
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Cysteine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Adrenergic beta-Antagonists

ClinicalTrials.gov processed this record on April 22, 2014