The Effects of Iontophoresed Vasoactive Drugs on Cutaneus Blood Flow (Jonto01)

May 8, 2026 updated by: Daniel Wilhelms, University Hospital, Linkoeping

A Non-randomized Experimental Study of Optically Registered Pharmacodynamic Responses During Iontophoresis of Vasoactive Substances to the Skin of Healthy Volunteers

Many acute and chronical medical conditions, such as, shock, sepsis, diabetes, hypertonia, and cardiovascular disease are associated with a perturbated or lost ability of regulating the diameter of the blood vessels. These changes in regulatory function can be seen especially in the smaller vessels in the body. It is therefore clinically relevant to develop investigation models that can detect and quantify such changes at an early stage.

Historically, basic vascular function was investigated by mounting a section of a blood vessel on a tension sensor, submerging it in a temperature controlled and buffered solution to which vasoactive substances were added. This in vitro model has contributed substantially to our current knowledge of vascular pharmacology and function. However, using this method means that the vessel is removed from its natural environment and, hence no longer influenced by systemic or local mediators for controlling vessel diameter.

The present study aims to investigate the local changes in blood flow and concentration of red blood cells of the superficial vessels in the skin of the forearm of healthy volunteers in response to various vasoactive substances. The purpose is to better understand how the regulation of diameter works in and to find a model that can give an early warning to when it does not function optimally.

The vasoactive substances will be delivered through the skin to the vascular bed by a non-invasive method called iontophoresis. An electrode chamber containing a solution of the substance to be studied is placed on the subject's skin by double adhesive tape. The chamber comes with a transparent lid that prevents leakage and enables supervision of the effect on the underlying vasculature. When a voltage is applied the charged drug molecules begin to move through the skin and interact with the vessels. In the present study, a total electrical dose of 12 millicoulomb (mC) is going to be used (600 seconds x 0.02 milliampere).

The effect of the applied drug is measured using two non-contact, optical measurement techniques.

A better understanding of the pharmacology and regulation of blood vessels may lead to the developement of techniques that allow earlier detection of perturbations in vessel regulation and the onset of preventive medical treatment.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

A non-randomised study to investigate how 6 different vasoactive substances administrated in 5 different concentrations, and with repeated administration affect the cutaneous superficial vessels. The primary aim is to investigate dose-response mechanisms by use of two non-invasive optical measurement technologies.

The substances are administrated by iontophoresis using a protocol with a current of 0.02 mA for 600 seconds, at a total electrical charge of 12 mC. Each drug is diluted using sterile water into five concentration (1%, 0.1%, 0.01%, 0.001% and 0.0001%). In the sixth chamber only sterile water will be administrated.

An electrode chamber per concentration is attached to the skin of each subject's forearm and each concentration is administrated three times.

Only one substance at a time will be administrated.

The substances used are:

  • Acetylcholine - vasodilator (Miochol-E, 10mg/ml, Bausch and Lomb)
  • Noradrenaline - vasoconstrictor (Noradrenaline, 10mg/ml, Pfizer)
  • Phenylephrine - vasoconstrictor (Phenylephrine, 10mg/ml, Unimedic)
  • Atropine - anticholinergic (Atropine, 10mg/ml, Bausch and Lomb)
  • Neostigmine - acetylcholineesterase inhibitor (Neostigmine, 10mg/ml, Unimedic Pharma)
  • Dilutor: sterile water (Sterile water, 100 ml, Braun)

Iontophoresis protocol: 0.02 mA x 600 seconds x 3 repetitions per drug concentration and localization. Each iontophoretic pulse is preceded by a baseline registration and followed by a 30 minutes wash-out/recovery period.

Vascular effects are continuously, non-invasively and indirectly measured using tissue viability imaging (TiVi, cross-polarized diffuse reflectance spectroscopy) and multi-exposure laser speckle contrast imaging (MELSCI). The optical measurement modalities are placed at a distance of approximately 30 cm above the skin surface so that the vascular responses can be measured in three electrode chambers simultaneously for the duration of the test (120 minutes).

TiVi settings - 1 image/minute at 6000 x 4000 pixels MELSCI settings - 15.6 frames/second at 1024 x 1000 pixels

Study Type

Interventional

Enrollment (Actual)

31

Phase

  • Not Applicable

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

  • Sweden
    • Östergötland County
      • Linköping, Östergötland County, Sweden, 58185
        • University Hospital Linköping

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

Yes

Description

Inclusion Criteria:

  • Healthy
  • No ongoing medication
  • No skin disease or other skin afflictions
  • Informed, voluntary participation

Exclusion Criteria:

  • Ongoing medication (contraceptives excluded)
  • Hypertonia, skin disease or skin afflictions, cardiovascular disease, pregnancy
  • Damaged skin, bruises, scar tissue or tattoos on the skin of the forearms
  • Smoking (6 months prior to study onset, or more than 100 cigarettes in life)
  • Snus (6 months prior to study onset)
  • Use of nicotine products (gum, patch, et cetera) 6 months prior to study onset
  • Blood pressure above 140/90
  • Coffee, tea, alcohol or strenuous physical activity on the day of the study
  • Not fasting for 2 hours prior onset of the study

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

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Vascular effects of iontophoresed vasoactive substances

Iontophoretically administered vasoactive substances in five concentrations (1%,0.1%,0.01%,0.001%, 0.0001%) dissolved in sterile water. Each concentration of the drug is separately administered using a electrical charge of 12 millicoulomb (mC) (600 seconds x 0.02 milliampere) for 3 repeated pulses (total electrical charge 36 mC). Each iontophoresis pulse is separated by a 30 minute wash-out period.

Vasoactive substances:

  • Miochol-E (Acetylcholine),10 mg/ml, Bausch & Lomb
  • Methacholine chloride, 100 mg/ml, APL
  • Norepinephrine, 1 mg/ml, Pfizer
  • Phenylephrine, 10 mg/ml, Unimedic
  • Atropine, 10 mg/ml, Bausch & Lomb
  • Neostigmine, 2.5 mg/ml, Unimedic Pharma
  • Sterile water, 100 ml, Braun
Drug: Acetylcholine
Iontophoretic administration of 5 different concentrations of acetylcholine
Other Names:
  • Miochol-E, 10mg/ml, Bausch and Lomb
Drug: Norepinephrine
Iontophoretic administration of 5 different concentrations of norepinephrine
Other Names:
  • Norepinephrine, 1 mg/ml, Pfizer
Drug: Phenylephrine
Iontophoretic administration of 5 different concentrations of phenylephrine
Other Names:
  • Phenylephrine, 10 mg/ml, Unimedic
Drug: Atropine
Iontophoretic administration of 5 different concentrations of atropine
Other Names:
  • Atropine, 10 mg/ml, Bausch & Lomb
Drug: Neostigmine
Iontophoretic administration of 5 different concentrations of neostigmine
Other Names:
  • Neostigmine, 2.5 mg/ml, Unimedic Pharma
Drug: Sterile water
Iontophoretic administration of sterile water
Other Names:
  • Sterile water, 100 ml, Braun

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Locally induced changes in red blood cell concentration and movement due to iontophoresis of vasoactive substances.
Time Frame: Measured prior the onset of iontophoresis (baseline), then continuously for the duration of the iontophoretic pulse (10 minutes) and for the 30 minute wash-out period following each iontophoretic pulse.
Optically derived arbitrary values that correlate to the concentration and movement of red blood cells in the vessels.
Measured prior the onset of iontophoresis (baseline), then continuously for the duration of the iontophoretic pulse (10 minutes) and for the 30 minute wash-out period following each iontophoretic pulse.

Collaborators and Investigators

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

Sponsor

University Hospital, Linkoeping

Investigators

  • Principal Investigator: Daniel Wilhelms, Phd, Linkoeping University

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)

April 1, 2019

Primary Completion (Actual)

October 15, 2021

Study Completion (Actual)

October 31, 2021

Study Registration Dates

First Submitted

February 22, 2021

First Submitted That Met QC Criteria

February 25, 2021

First Posted (Actual)

March 2, 2021

Study Record Updates

Last Update Posted (Actual)

May 13, 2026

Last Update Submitted That Met QC Criteria

May 8, 2026

Last Verified

February 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2018-004624-11

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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