Jonto01: The Effects of Iontophoresed Vasoactive Drugs on Cutaneus Blood Flow

Sponsor

University Hospital, Linkoeping (Other)

Overall Status

Recruiting

CT.gov ID

NCT04777383

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

2.7

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Cardiovascular Diseases Vascular Diseases	Drug: Acetylcholine Drug: Norepinephrine Drug: Phenylephrine Drug: Atropine Drug: Neostigmine Drug: Sterile water	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

90 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Iontophoresis of vasoactive substances in 5 different concentrations. Each concentration is administrated 3 times to the same localisation.Iontophoresis of vasoactive substances in 5 different concentrations. Each concentration is administrated 3 times to the same localisation.

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

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

Actual Study Start Date :

Apr 1, 2019

Anticipated Primary Completion Date :

Dec 31, 2021

Anticipated Study Completion Date :

Dec 31, 2021

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Locally induced changes in red blood cell concentration and movement due to iontophoresis of vasoactive substances. [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.