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| Sponsor: | University of Edinburgh |
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| Collaborators: |
Chief Scientist Office of the Scottish Government NHS Lothian |
| Information provided by: | University of Edinburgh |
| ClinicalTrials.gov Identifier: | NCT00901563 |
Purpose
Hypothesis - Rotigaptide will improve endothelial function in the context of endothelial dysfunction.
The lining of blood vessels (endothelium) can react to hormones in the blood stream causing the blood vessel muscle to relax (vasodilatation) and allow more blood to flow. The nitric oxide and prostacyclin pathways are well documented in this process. However, evidence points to the existence of a third powerful relaxant called endothelium derived hyperpolarising factor (EDHF) but its identity and mechanism of action have proved elusive. As well as causing blood vessels to relax and more blood to flow, EDHF may be involved in the endothelium signaling, triggering release of a specialised clot dissolving factor called tissue plasminogen activator (t PA). t PA is important to ensure small clots, which are constantly being formed in the circulation, are rapidly dissolved and do not grow large enough to cause heart attacks and strokes.
Evidence points towards the requirement for 'gap junctions' in the mediation of EDHF responses. Gap junctions are specialised pores which allow small molecules and charge to pass between cells. They are found between endothelial cells and the underlying muscle of the blood vessel. A drug called Rotigaptide has been developed to cause gap junctions to open. It has been safely administered in healthy volunteers and is now in a Phase II drug trial. By opening gap junctions the investigators hypothesise that it could increase EDHF mediated activity and vasodilatation. It represents a useful tool with which to examine the role of gap junctions in EDHF activity in vivo.
Previously the investigators have demonstrated that rotigaptide does not contribute to endothelial function in healthy volunteers. The investigators now wish to examine the effect of rotigaptide in conditions of endothelial dysfunction. By limiting the blood flow to the arm for 20mins the ability of the blood vessel to vasodilate is impaired. By administering an intra−arterial rotigaptide infusion the investigators want to assess any functional preservation.
| Condition | Intervention |
|---|---|
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Vascular Disease Heart Disease |
Drug: Rotigaptide Other: Forearm vascular study |
| Study Type: | Interventional |
| Study Design: | Basic Science, Randomized, Double Blind (Subject, Investigator), Placebo Control, Crossover Assignment, Safety/Efficacy Study |
| Official Title: | Gap Junction Potentiation of Endothelial Function With Rotigaptide in the Human Forearm Arterial Circulation - Effects of Ischaemia Induced Endothelial Dysfunction |
| Estimated Enrollment: | 24 |
| Study Start Date: | March 2009 |
| Estimated Primary Completion Date: | March 2010 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
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Rotigaptide: Active Comparator
Prior to 20 mins of ischaemia induced by a blood pressure cuff inflated to 200 mmHg around the upper non-dominant arm, rotigaptide will be infused for 30mins. During the ischaemic period no drug will be infused but the infusion will be restarted once the blood pressure cuff has been deflated and blood flow returns to the limb.
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Drug: Rotigaptide
Prior to 20 mins of ischaemia induced by a blood pressure cuff inflated to 200 mmHg around the upper non-dominant arm, rotigaptide will be infused for 30mins. During the ischaemic period no drug will be infused but the infusion will be restarted once the blood pressure cuff has been deflated and blood flow returns to the limb.
Other: Forearm vascular study
Forearm blood flow measured by venous occlusion plethysmography during interarterial infusion of substance P (2,4,8 pmol/min) or Acetylcholine (5, 10 , 20 micromol/min) . Venous blood sampling via cannula in antecubital fossa.
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Saline: Placebo Comparator
Saline will be infused through-out the study.
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Other: Forearm vascular study
Forearm blood flow measured by venous occlusion plethysmography during interarterial infusion of substance P (2,4,8 pmol/min) or Acetylcholine (5, 10 , 20 micromol/min) . Venous blood sampling via cannula in antecubital fossa.
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Show Detailed Description Eligibility| Ages Eligible for Study: | 18 Years to 64 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
Exclusion Criteria:
Contacts and Locations| Contact: Gareth D Barnes, MBChB | 0044 7967 621 980 | gareth.barnes@ed.ac.uk |
| United Kingdom | |
| Clincial Research Facility, Royal Infirmary of Edinburgh, 51 Little France Cresc | Recruiting |
| Edinburgh, United Kingdom, EH16 4SA | |
| Contact: Gareth D Barnes, MBChB 0044 7967 621 980 gareth.barnes@ed.ac.uk | |
| Principal Investigator: Gareth D Barnes, MBChB | |
| Sub-Investigator: Ninian N Lang, MBChB | |
| Sub-Investigator: Christian M Pederesen, MD | |
| Sub-Investigator: N L Cruden, MBChB | |
| Study Director: | David E Newby, MD | University of Edinburgh |
More Information
| Responsible Party: | University of Edinburgh ( Dr Gareth Barnes, Research Fellow ) |
| Study ID Numbers: | CZB/4/520/b |
| Study First Received: | May 13, 2009 |
| Last Updated: | May 13, 2009 |
| ClinicalTrials.gov Identifier: | NCT00901563 History of Changes |
| Health Authority: | United Kingdom: Research Ethics Committee |
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Gap Junctions Rotigaptide Ischaemia reperfusion t-PA |
Fibrinolysis Endothelial function Venous occlusion plethysmography |
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Heart Diseases Vascular Diseases Cardiovascular Diseases |
