The Effects of Iontophoresed Vasoactive Drugs on Cutaneus Blood Flow

Cardiovascular Diseases Clinical Trial

— Jonto01  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04777383
• Other study ID #: 2018-004624-11
• Status: Recruiting
• Phase: N/A
• Start date: April 1, 2019
• Est. completion date: December 31, 2021

Study information

• Verified date: February 2021
• Source: University Hospital, Linkoeping
• Contact: Daniel Wilhelms, Phd
• Phone: +46(0)101030000
• Email: daniel.wilhelms[@]liu.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: December 31, 2021
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Vascular Diseases

Intervention

Drug:
• Acetylcholine
Iontophoretic administration of 5 different concentrations of acetylcholine
• Norepinephrine
Iontophoretic administration of 5 different concentrations of norepinephrine
• Phenylephrine
Iontophoretic administration of 5 different concentrations of phenylephrine
• Atropine
Iontophoretic administration of 5 different concentrations of atropine
• Neostigmine
Iontophoretic administration of 5 different concentrations of neostigmine
• Sterile water
Iontophoretic administration of sterile water

Locations

Country	Name	City	State
Sweden	University Hospital Linköping	Linköping	Östergötland

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Linkoeping

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Locally induced changes in red blood cell concentration and movement due to iontophoresis of vasoactive substances.	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.