Gap Junction Potentiation of Endothelial Function With Rotigaptide

The recruitment status of this study is unknown because the information has not been verified recently.
Verified May 2009 by University of Edinburgh.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
Chief Scientist Office of the Scottish Government
NHS Lothian
Information provided by:
University of Edinburgh
ClinicalTrials.gov Identifier:
NCT00901563
First received: May 13, 2009
Last updated: NA
Last verified: May 2009
History: No changes posted
  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
Vascular Disease
Heart Disease
Drug: Rotigaptide
Other: Forearm vascular study

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: Gap Junction Potentiation of Endothelial Function With Rotigaptide in the Human Forearm Arterial Circulation - Effects of Ischaemia Induced Endothelial Dysfunction

Resource links provided by NLM:


Further study details as provided by University of Edinburgh:

Primary Outcome Measures:
  • Change in Substance P and ACh vasodilatation caused by potentiation of gap junction communication with Rotigaptide in the context of endothelial dysfunction [ Time Frame: Vasodilatation will be assesed before and after ischaemic periods ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in Substance P induced t PA release caused by potentiation of gap junction communication with Rotigaptide in the context of endothelial dysfunction [ Time Frame: Venous blood samles will be taken at regular time points throught the protocol ] [ Designated as safety issue: No ]

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
Active Comparator: 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.
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.
Placebo Comparator: Saline
Saline will be infused through-out the study.
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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  Eligibility

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy volunteers aged between 18-64 years.

Exclusion Criteria:

  • Lack of informed consent
  • Age <18 or >64 years
  • Current involvement in a clinical trial
  • Clinically significant comorbidity: heart failure, hypertension, known hyperlipidaemia, diabetes mellitus, asthma, coagulopathy or bleeding disorders*
  • Smoker*
  • Current intake of aspirin, other non steroid anti inflammatory medications or vasodilators*
  • Recent infective/inflammatory condition*
  • Women of child bearing age
  • Recent blood donation (preceding three months) *All cause confounding effects on vascular/endothelial function.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00901563

Contacts
Contact: Gareth D Barnes, MBChB 0044 7967 621 980 gareth.barnes@ed.ac.uk

Locations
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         
Sponsors and Collaborators
University of Edinburgh
Chief Scientist Office of the Scottish Government
NHS Lothian
Investigators
Study Director: David E Newby, MD University of Edinburgh
  More Information

No publications provided

Responsible Party: Dr Gareth Barnes, Research Fellow, University of Edinburgh
ClinicalTrials.gov Identifier: NCT00901563     History of Changes
Other Study ID Numbers: CZB/4/520/b
Study First Received: May 13, 2009
Last Updated: May 13, 2009
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by University of Edinburgh:
Gap Junctions
Rotigaptide
Ischaemia reperfusion
t-PA
Fibrinolysis
Endothelial function
Venous occlusion plethysmography

Additional relevant MeSH terms:
Heart Diseases
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on August 28, 2014