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Trial record 5 of 232 for:    EDN1

Role of Endothelin-1 in Flow-mediated Dilatation (Endothelin)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02086253
Recruitment Status : Completed
First Posted : March 13, 2014
Last Update Posted : March 24, 2015
Sponsor:
Information provided by (Responsible Party):
University Hospital, Rouen

Tracking Information
First Submitted Date  ICMJE February 18, 2014
First Posted Date  ICMJE March 13, 2014
Last Update Posted Date March 24, 2015
Study Start Date  ICMJE February 2014
Actual Primary Completion Date May 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 11, 2014)
Effect of ETB receptor blockade on flow-mediated dilatation [ Time Frame: One hour after BQ-788 brachial infusion ]
This study will evaluate the effect of the ETB receptor blockade on the magnitude of the flow-mediated dilatation of the radial artery in response to distal skin heating in 8 healthy subjects. Radial artery diameter and blood flow will be measured by high-resolution echotracking coupled to Doppler.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02086253 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 11, 2014)
  • Effect of ETA and ETA/ETB receptor blockade on flow-mediated dilatation [ Time Frame: One hour after BQ-123 alone or with BQ-788 brachial infusion ]
    This study will evaluate the effect of ETA receptor and combined ETA/ETB receptor blockade on the magnitude of the flow-mediated dilatation of the radial artery in response to distal skin heating in 8 healthy subjects. Radial artery diameter and blood flow will be measured by high-resolution echotracking coupled to Doppler.
  • Effect of ETA and/or ETB receptor blockade on ET-1, NO and EET bioavailability [ Time Frame: One hour after BQ-788 and/or BQ-123 brachial infusion ]
    This study will evaluate the effect of ETA and/or ETB blockade on the variations in the local concentrations of ET-1, NO and EETs during sustained flow-mediated dilation in 8 healthy subjects. For this purpose, local blood samples will be drawn before (34°C) and at the end of hand skin heating (44°C). Plasma nitrite, indicator of NO availability will be quantified by chemiluminescence.Plasma EETs will be quantified by LC-MS. Plasma ET-1 will be quantified with an immunoassay.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Role of Endothelin-1 in Flow-mediated Dilatation
Official Title  ICMJE Role of Endothelin-1 in Mediating Flow-mediated Dilatation of Conduit Arteries During Sustained Hyperemic Stimulation
Brief Summary Endothelial dysfunction of conduit arteries contributes to the increased morbidity and cardiovascular mortality in patients with essential hypertension and appears increasingly as an independent therapeutic target. We have shown previously that besides a decrease in the availability of NO and other endothelium-derived vasodilators factors, the epoxyeicosatrienoic acids, an increase in the vasoconstrictor endothelin-1 (ET-1) may play a role in the pathophysiology of this endothelial dysfunction. Indeed, the local concentrations of endothelin-1 during the endothelium-dependent dilation of the radial artery in response to a sustained increase in blood flow decreased significantly in healthy volunteers controls but not in hypertensive patients. This lack of adaptation of the endothelinergic system could be due to a decreased clearance of endothelin-1 by endothelial ETB receptors, potentiating the vasoconstrictor action of endothelin-1 mediated by ETA receptor activation at the muscular level. However, to validate this hypothesis , it is needed to demonstrate the physiological role of ETA receptor and ETB in sustained flow-mediated dilatation of conduit arteries.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Condition  ICMJE Healthy Conditions
Intervention  ICMJE Drug: BQ-788 and/or BQ-123
Study Arms  ICMJE
  • Experimental: BQ-788
    Effect of BQ-788 on the magnitude of sustained flow-mediated dilatation
    Intervention: Drug: BQ-788 and/or BQ-123
  • Experimental: BQ-123
    Effect of BQ-123 on the magnitude of sustained flow-mediated dilatation
    Intervention: Drug: BQ-788 and/or BQ-123
  • Experimental: BQ-788 + BQ-123
    Effect of BQ-788+BQ-123 on the magnitude of sustained flow-mediated dilatation
    Intervention: Drug: BQ-788 and/or BQ-123
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 11, 2014)
8
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE May 2014
Actual Primary Completion Date May 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male, Caucasian, aged 18 to 35 years
  • Non-Smoking
  • Resting heart rate> 50 and <90 bpm
  • SBP <140 mmHg and DBP <90 mm Hg at rest in the supine position for 10 minutes
  • Normal ECG

Exclusion Criteria:

  • Known allergy
  • Intolerance to glyceryl trinitrate
  • Intolerance to lidocaine
  • Family history of hypertension
  • Excessive alcohol consumption ( more than 50 g / day)
  • Addiction or presumption of illicit drug use
  • Subject refusing blood samples for serology of hepatitis B , C and HIV
  • History of illness or psychological or sensory abnormality that may prevent the subject to understand the requirements for participation in the protocol or prevents giving informed consent
  • Metabolic or endocrine disease
  • Immunological diseases
  • Renal or hepatic impairment
  • Ischemic or obstructive heart disease
  • Neoplastic disease
  • Gastrointestinal disease
  • Neurological disease , intracranial hypertension , seizure disorders
  • Compulsive overeating , bulimia, anorexia
  • Severe psychiatric illness
  • Presence of a clinically significant abnormality in laboratory tests carried out at the inclusion visit .
  • HBs Ag , HCV Ab , Ac HIV 1 or HIV 2 positive .
  • The use of any drug in the range of less than 5 half-life time, in particular betablockers, sildenafil, cimetidine, amiodarone .
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 35 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02086253
Other Study ID Numbers  ICMJE 2013/161/HP
2013-004425-87 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University Hospital, Rouen
Study Sponsor  ICMJE University Hospital, Rouen
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Robinson JOANNIDES, Doctor Chu - Hôpitaux de Rouen
PRS Account University Hospital, Rouen
Verification Date March 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP