Cardiovascular DiseasesJonto01NCT04777383
The Effects of Iontophoresed Vasoactive Drugs on Cutaneus Blood Flow
A study testing Acetylcholine, Norepinephrine and Phenylephrine in people with Cardiovascular Diseases and Vascular Diseases, run by University Hospital, Linkoeping at 1 site in Sweden.
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. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Cardiovascular Diseases, Vascular Diseases
- What is being tested?
- Acetylcholine, Norepinephrine and Phenylephrine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteSweden
- Study dates
- 1 Apr 2019to 31 Oct 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy
- No ongoing medication
- No skin disease or other skin afflictions
- Informed, voluntary participation
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Sweden1 site
University Hospital Linköping
Linköping, Östergötland County, 58185
About this study
Official title: 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.
Read more
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.
Read the 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
- Conditions
- Cardiovascular Diseases, Vascular Diseases
- Being tested
- Acetylcholine, Norepinephrine, Phenylephrine, Atropine, Neostigmine
- Keywords
- iontophoresis, pharmacology, tissue viability imaging, multi-exposure laser speckle contrast imaging
- Medical subject headings
- Cardiovascular Diseases, Vascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcetylcholineDrug
Also called Miochol-E, 10mg/ml, Bausch and Lomb
Iontophoretic administration of 5 different concentrations of acetylcholine
NorepinephrineDrug
Also called Norepinephrine, 1 mg/ml, Pfizer
Iontophoretic administration of 5 different concentrations of norepinephrine
PhenylephrineDrug
Also called Phenylephrine, 10 mg/ml, Unimedic
Iontophoretic administration of 5 different concentrations of phenylephrine
AtropineDrug
Also called Atropine, 10 mg/ml, Bausch & Lomb
Iontophoretic administration of 5 different concentrations of atropine
NeostigmineDrug
Also called Neostigmine, 2.5 mg/ml, Unimedic Pharma
Iontophoretic administration of 5 different concentrations of neostigmine
Sterile waterDrug
Also called Sterile water, 100 ml, Braun
Iontophoretic administration of sterile water
| Study group | Role | What they receive |
|---|---|---|
| Vascular effects of iontophoresed vasoactive substances | Experimental | 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 Receives: Drug: Acetylcholine; Drug: Norepinephrine; Drug: Phenylephrine; Drug: Atropine; Drug: Neostigmine; Drug: Sterile water |
What is being measured
The primary outcome is the main question the study is designed to answer.
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: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2021
- Study start1 Apr 2019
- Primary completion15 Oct 2021
- Study completion31 Oct 2021
Why it stopped: The study was terminated prematurely due to insufficient operational resources to continue trial conduct and completion. The decision was unrelated to safety concerns or study outcomes.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cardiovascular DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Iontophoresis of vasoactive substances in 5 different concentrations. Each concentration is administrated 3 times to the same localisation.
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Linkoeping
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Daniel Wilhelms, University Hospital, Linkoeping
- Investigators
- Daniel Wilhelms, Phd, Principal investigator, Linkoeping University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04777383
- Sponsor's protocol ID
- 2018-004624-11
- Other IDs
- 2018
- Acronym
- Jonto01
- Status last verified
- Feb 2021
- First submitted
- 22 Feb 2021
- Last updated
- 13 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Henricson J, Sjoberg F, Iredahl F, Stromberg T, Wilhelms D. In vivo dose-response analysis to acetylcholine: pharmacodynamic assessment by polarized reflectance spectroscopy. Sci Rep. 2022 Apr 21;12(1):6594. doi: 10.1038/s41598-022-10617-x.
PubMed 35449189
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Non-randomized Experimental Study of Optically Registered Pharmacodynamic Responses During Iontophoresis of Vasoactive Substances to the Skin of Healthy Volunteers
- ClinicalTrials.gov ID
- NCT04777383
- Acronym / sponsor ID
- Jonto01 / 2018-004624-11
- Conditions
- Cardiovascular Diseases, Vascular Diseases
- Keywords
- iontophoresis, pharmacology, tissue viability imaging, multi-exposure laser speckle contrast imaging
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated prematurely due to insufficient operational resources to continue trial conduct and completion. The decision was unrelated to safety concerns or study outcomes.
- Enrolment
- 31 participants (actual)
- Lead sponsor
- University Hospital, LinkoepingUniversity, hospital or other
- Study start
- 1 Apr 2019 (actual)
- Primary completion
- 15 Oct 2021 (actual)
- Study completion
- 31 Oct 2021 (actual)
- First posted
- 2 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Iontophoresis of vasoactive substances in 5 different concentrations. Each concentration is administrated 3 times to the same localisation.
| Arm | Type | Receives |
|---|---|---|
| Vascular effects of iontophoresed vasoactive substances | Experimental | Drug: Acetylcholine, Drug: Norepinephrine, Drug: Phenylephrine, Drug: Atropine, Drug: Neostigmine, Drug: Sterile waterIontophoretically 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 |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Healthy
- No ongoing medication
- No skin disease or other skin afflictions
- Informed, voluntary participation
Key exclusion criteria (9 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AcetylcholineAlso: Miochol-E, 10mg/ml, Bausch and LombIontophoretic administration of 5 different concentrations of acetylcholine | Drug | Vascular effects of iontophoresed vasoactive substances |
| NorepinephrineAlso: Norepinephrine, 1 mg/ml, PfizerIontophoretic administration of 5 different concentrations of norepinephrine | Drug | Vascular effects of iontophoresed vasoactive substances |
| PhenylephrineAlso: Phenylephrine, 10 mg/ml, UnimedicIontophoretic administration of 5 different concentrations of phenylephrine | Drug | Vascular effects of iontophoresed vasoactive substances |
| AtropineAlso: Atropine, 10 mg/ml, Bausch & LombIontophoretic administration of 5 different concentrations of atropine | Drug | Vascular effects of iontophoresed vasoactive substances |
| NeostigmineAlso: Neostigmine, 2.5 mg/ml, Unimedic PharmaIontophoretic administration of 5 different concentrations of neostigmine | Drug | Vascular effects of iontophoresed vasoactive substances |
| Sterile waterAlso: Sterile water, 100 ml, BraunIontophoretic administration of sterile water | Drug | Vascular effects of iontophoresed vasoactive substances |
Primary outcome
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.
Results and safety
The study was stopped early (reason given: The study was terminated prematurely due to insufficient operational resources to continue trial conduct and completion. The decision was unrelated to safety concerns or study outcomes.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2026.
- Derived from this study: PubMed 35449189Henricson J, Sjoberg F, Iredahl F, Stromberg T, Wilhelms D. In vivo dose-response analysis to acetylcholine: pharmacodynamic assessment by polarized reflectance spectroscopy. Sci Rep. 2022 Apr 21;12(1):6594. doi: 10.1038/s41598-022-10617-x.
Related trials for Cardiovascular Diseases
Active, not recruitingPhase 3
ENDOTHELION Study Group: Effect of Bosentan in NAION Patients
Ischemic Optic Neuropathy
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Not yet recruitingPhase 2
Study of YKST02 in Adults With Relapsed or Refractory Multiple Myeloma
Relapsed or Refractory Multiple Myeloma (RRMM)
RecruitingPhase 2
Engaging T-cells to Eliminate MRD in Newly Diagnosed Myeloma Optimizing Response With Talquetmab and Teclistamab (ROTATE)
Multiple Myeloma
Recruiting
PAW-Hydrogel for Chronic Wound Healing
Diabetic Foot Ulcer (DFU), Pressure Ulcer (PU)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniel Wilhelms, Phd principal investigator
Linkoeping University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Acetylcholine, Norepinephrine and Phenylephrine in people with Cardiovascular Diseases and Vascular Diseases, run by University Hospital, Linkoeping at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: The study was terminated prematurely due to insufficient operational resources to continue trial conduct and completion. The decision was unrelated to safety concerns or study outcomes.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04777383, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2026.