Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04027959 |
| Other study ID # |
KOR-17-34 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
October 5, 2017 |
| Est. completion date |
November 1, 2018 |
Study information
| Verified date |
December 2020 |
| Source |
James J. Peters Veterans Affairs Medical Center |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
STUDY DESIGN: Phase I Clinical Trial The researchers set out to assess the effectiveness of
transdermal iontophoretic administration of Vitamin B12 (V.B12) under three different skin
preparatory conditions.
SETTING: James J. Peters Veterans Affairs Medical Center (Bronx, NY) BACKGROUND: Poor skin
permeability precludes the use of transdermal route from being used in common clinical
practice for rapid and precise administration of medications through intact skin that are
expected to have a systemic effect. The researchers determined the relative effectiveness of
an unconventional transdermal iontophoresis technique for the administration of Vitamin B12
(V.B12) under three different skin preparatory conditions.
METHODS: During this study, Vitamin B12 (V.B12) was administered through the skin of
volunteer human research subjects. Iontophoresis was used as transdermal medication delivery
modality after pre-treatment of the skin in 3 different ways. The sequence of skin
preparations was arranged in a random order for each subject. Method 1 was called "No Prep",
serving as the control approach; method 2 was called "Oleic Acid" application to the skin for
40 minutes; and method 3 was hair "Epilation" (e.g. hair removal by plucking). Fifteen
milligrams of aqueous solution of V.B12 was administered through intact, previously unused
skin of an anterior thigh during all 3 tests. Chemoluminescence, on an automated laboratory
reader Advia Centaur-XP, was used to determine the serum concentration of V.B12 prior to and
after transdermal iontophoretic delivery. All 3 experiments were performed on the same day
within an hour of each other. The subject's blood was drawn prior and 10 minutes after the
20-minute long sessions of transdermal V.B12 iontophoresis. We were able to calculate the
increase in serum V.B12 concentration and based on estimated blood volume, the total quantity
and percent dose delivered systemically.
Description:
In order to quantify the changes in skin permeability to drugs delivered by ION under three
different preparatory conditions, we used V.B12 as a model substance. Its choice was dictated
by its inherent safety, positive charge and quantification of serum concentration readily
available through our clinical laboratory. We compared the effects of unprepared skin (No
Prep), oil-soaked skin [ref. 9-12] (Oleic Acid) and skin from which hair have been plucked
out of (Epilation), on the serum concentrations of V.B12 before and after administration via
ION.
Veterans and non-Veterans without SCI were recruited for the study comparing the three skin
preparation methods. This prospective, skin preparatory method sequence-randomized study was
approved by the Institutional Review Board of the James J. Peters VA Medical Center
(JJPVAMC). The ION equipment used was a standard FDA-approved wired ION controller unit (IBOX
by Dynatronics) and 4mL ION electrodes by (ionto+ by Richmar). The skin was prepared using 1
of the 3 techniques, performed in a random order. Each subject was assigned a 2-digit
sequential number. A random-numbers table was used to assign the sequence of methods to each
subject. A single positive electrode patch containing 4mL of a water-based solution with 15mg
of V.B12 was used per experiment. One negative electrode patch was also used to complete the
circuit. Blood was drawn prior to the first administration. Thirty minutes after the start of
the ION delivery of the V.B12 through the skin of anterior thigh, the blood was drawn again.
The blood was centrifuged for 5 minutes and delivered to the clinical laboratory for testing
without delay. Serum concentration of V.B12 was measured using chemoluminescence on an
automated laboratory reader Advia Centaur-XP. The experiments were conducted sequentially in
a timely fashion, performed on the same day and within a span of 3 hours. Blood was drawn for
a total of 4 times per subject.
The "No Prep" technique was performed by simply wiping the two skin surfaces on an anterior
thigh, where the electrodes were later attached, with two-70% isopropyl alcohol prep. pads.
The skin surface destined for positive electrode application was sprayed with a thin layer of
20% Benzocaine (Americaine aerosol spray can) and covered with an occlusive plastic film for
10 minutes. The film was then removed and the skin was cleansed with water-moistened paper
towel, followed by one alcohol prep. pad.
The "Oleic Acid" technique involved first wiping the two skin patches and later soaking the
skin patch, where the positive electrode was going to be placed, with oil called oleic acid
for 40 minutes. The oil was then wiped off with a paper napkin and an alcohol pad. That same
skin area was sprayed with a thin layer of 20% Benzocaine (Americaine aerosol spray
container) and covered with an occlusive plastic film for 10 minutes. The film was then
removed and the skin was cleansed with water-moistened paper towel, followed by one alcohol
prep.
The "Hair Epilation" technique involved first wiping the two skin patches with 2-70%
isopropyl alcohol skin preps and sprayed with a thin layer of 20% Benzocaine (Americaine
aerosol spray container) and covered with an occlusive plastic film for 10 minutes. The film
was removed and the skin was cleansed with de-ionized water followed by alcohol prep. Hair
removal, using an epilator machine (Remington EP 7030), was performed by clearing an area of
5x5cm or 2x2 inch square. The epilated area was then covered with a thin layer of 0.2% Sodium
Lauryl Sulfate (SLS) in de-ionized water.
After each of the skin preparations and without delay, 15mg of methylcobalamin dissolved in
4mL of de-ionized water soaked into the anode patch reservoir was applied to the designated
skin of the proximal anterior thighs. The 7x7cm skin area under the negative electrode was
wiped with an alcohol pad and 0.5mL of 1% citric acid dissolved in 0.9% normal saline
solution was applied to the negative electrode's skin contact surface. The return (negative)
electrode was then attached to the skin 10cm from the positive electrode.
An elevated room temperature of 73-78 degrees Fahrenheit (25 degrees Celsius) was maintained
in the room for the purposes of maintaining adequate blood flow in the peripheral dermal
capillaries. No exclusion criteria for diseases that decrease capillary perfusion such as
diabetes have been utilized. As a result, 2 of the 10 subjects who participated in this study
had a diagnosis of Diabetes Mellitus type 2.
IBOX ION device was attached to the electrodes by way of wire leads and a multimeter was
attached to the electrodes in parallel in order to record the skin's electrical resistivity
prior to and after ION. Throughout the 20-minute ION session, voltage exerted by the IBOX was
recorded at regular intervals. The voltage was automatically adjusted by the IBOX to deliver
a pre-set constant electrical current of 4mA/minute. Throughout the procedure subjects were
asked about the presence of any sensations associated with the ION including effects of the
medication being administered.
