A Non-randomized Experimental Study of Optically Registered Pharmacodynamic Responses During Iontophoresis of Vasoactive Substances to the Skin of Healthy Volunteers
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 发起方
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Locally induced changes in red blood cell concentration and movement due to iontophoresis of vasoactive substances.
研究概览
简要总结
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.
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •No ongoing medication
- •No skin disease or other skin afflictions
- •Informed, voluntary participation
排除标准
- •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
研究组 & 干预措施
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
干预措施: Atropine (Drug)
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
干预措施: Norepinephrine (Drug)
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
干预措施: Acetylcholine (Drug)
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
干预措施: Phenylephrine (Drug)
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
干预措施: Neostigmine (Drug)
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
干预措施: Sterile water (Drug)
结局指标
主要结局
Locally induced changes in red blood cell concentration and movement due to iontophoresis of vasoactive substances.
时间窗: 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.
次要结局
未报告次要终点
研究者
Daniel Wilhelms
Principal investigator
University Hospital, Linkoeping