Influence of Nitric Oxide on Flow Mediated Dilation

February 17, 2020 updated by: Roland E. Schmieder, University of Erlangen-Nürnberg Medical School

Single-centre, Single-blind, Randomized, Controlled, Cross-over Study to Analyze the Influence of Nitric Oxide on Flow Mediated Dilation

Flow-mediated vasodilation (FMD) has become one of the most widely assessed parameter to analyze endothelial function. The peripheral endothelial function as assessed by FMD correlates with coronary artery endothelial function and moreover, impaired FMD has been revealed to be good predictor for cardiovascular events in patients beyond cardiovascular risk factors and in patients with coronary artery disease.

This non-invasive technique measures the ability of the arteries to respond with endothelial release of vasoactive factors during reactive hyperemia. In this study the goal is to analyze in a clinical trial to what extend nitric oxide contribute to FMD by measuring FMD before and after blocking the release of nitric oxide. FMD is measured using a semi-automatic device named UNEX, recently developed in Japan. This semi-automatic ultrasound system represents a new development that overcomes the limitation of classic systems.

The hypothesis of this study is that FMD response is mostly nitric oxide dependent. To prove this hypothesis, overall 20 healthy male volunteers are included in this study. Total duration of this study for each volunteer is 2-4 weeks with total 3 visits at the Clinical Research Unit (CRC) of the Department of Nephrology, University of Erlangen-Nuremberg.

This study is important to better understand the mechanism of any kind of impaired FMD by cardiovascular risk factors and diseases and to better interpret impaired FMD assessed by UNEX.

Study Overview

Status

Completed

Conditions

Detailed Description

The assessment of endothelial function is crucial, as its dysfunction is described as a key pathological condition associated with many diseases leading to arteriosclerosis. Flow-mediated vasodilation (FMD) has become one of the most widely assessed parameter to analyze endothelial function. Celermajer et al. was the first to measure the FMD-response in vivo by ultrasound. This non-invasive technique measures the ability of the arteries to respond with endothelial release of vasoactive factors during reactive hyperemia.

The peripheral endothelial function as assessed by FMD correlates with coronary artery endothelial function. Impaired FMD has been revealed to be good predictor for cardiovascular events in patients beyond cardiovascular risk factors and in patients with coronary artery disease. It is also predictive for the extent and severity of coronary atherosclerosis.

Beyond the predictive nature of FMD, several studies have been reported on the effect of pharmacologic or physiologic interventions on FMD. For example weight loss and exercise increased FMD in overweight and obese patients with coronary heart disease.

Impaired FMD is mainly characterized by reduced bioavailability of different vasodilators due to oxidative stress. Of these vasodilators nitric oxide plays the major role, but its contribution to FMD is inconclusive. Studies to clarify the role of nitric oxide on FMD have been done with various methods, which require extensive training and standardization. Operator, study preparation, image acquisition and site selection, sphygmomanometer probe position, cuff occlusion time, the accurate use of edge-detection software as well as the correct characterization of the FMD response are all factors, which influence FMD measurement.

In this study the goal is to analyze in a clinical trial to what extent nitric oxide contribute to FMD by measuring FMD before and after blocking the release of nitric oxide. FMD is measured using a semi-automatic device named UNEX, recently developed in Japan. FMD measurements using UNEX implement the standards described in guidelines. This semi-automatic ultrasound system using an H-type ultrasound probe represents a new development that overcomes the limitation of classic systems (in particular the investigator-dependency of conventional, "hand-held" FMD measurements). This system comprised a 7.5-megahertz linear array transducer and a novel stereotactic probe-holding device (UNEX Co., Nagoya, Japan). Another advantage of this device is the continuous recording of B-mode images and A-mode waves of the artery in the longitudinal plane, so that continuous measurement of arterial diameter in the 4.5 min following cuff deflation occurs. A meta-analysis described that the nitric oxide dependency of the FMD response was the most in studies with FMD measurements at brachial artery with distal placement of the cuff and 5-minute occlusion. These criteria are fulfilled by UNEX. However, no data on nitric oxide dependency are available in the literature. Finally, this semi-automatic assessment of FMD has been shown to improve the precision and repeatability of the measurements.

The hypothesis of this study is that FMD response is mostly nitric oxide dependent and this could not be proven so far due to less sensitive conventional tool of FMD measurement.

Study Type

Observational

Enrollment (Actual)

20

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Erlangen, Germany, 91054
        • Clinical Research Center, Department of Nephrology and Hypertension, University of Erlangen-Nuremberg

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Sampling Method

Non-Probability Sample

Study Population

  • Young, male and healthy volunteers without any significant disease
  • Age of 18 and 45 years old

Description

Inclusion Criteria:

  • Young, male and healthy volunteers without any significant disease
  • Age of 18 and 45 years old
  • Informed consent has to be given in written form

Exclusion Criteria:

  • Uncontrolled hypertension or blood pressure >160/100 mmHg
  • Known Diabetes mellitus or fasting plasma glucose >126mg/dl
  • Subjects having any chronic treatment
  • Drug or alcohol abuse
  • Allergies or intolerance against the substances used in the study
  • Smokers or subjects had stopped smoking <1 year
  • Participation in another clinical study within 30 days prior to V1
  • Subject who do not give written consent, that pseudonymous data will be transferred in line with the duty of documentation and the duty of notification according to § 12 and § 13 Good Clinical Practice-V

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Only
  • Time Perspectives: Cross-Sectional

Cohorts and Interventions

Group / Cohort
Healthy individuals
Young, male and healthy volunteers without any significant disease

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent change of flow mediated dilation
Time Frame: 1 week after study inclusion
Percent change of flow mediated dilation (UNEX EF) in Response to L-NMMA/Saline infusion
1 week after study inclusion
Percent change of flow mediated dilation
Time Frame: 2 weeks after study inclusion
Percent change of flow mediated dilation (UNEX EF) in Response to L-NMMA/Saline infusion
2 weeks after study inclusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Erlangen-Nürnberg Medical School

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 14, 2018

Primary Completion (Actual)

March 1, 2019

Study Completion (Actual)

March 31, 2019

Study Registration Dates

First Submitted

October 11, 2018

First Submitted That Met QC Criteria

October 26, 2018

First Posted (Actual)

October 29, 2018

Study Record Updates

Last Update Posted (Actual)

February 18, 2020

Last Update Submitted That Met QC Criteria

February 17, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CRC2018UNEX

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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