The purpose of this study is to determine the clinical effectiveness of a low-power PEMF
device, a medium-power PEMF device and a high-power PEMF device as compared to a sham
device to treat leg ulcers resulting from venous stasis ("VSLU").

The Effects of Pulsed Elelectro-Magnetic Fields ("PEMF") in the Treatment of Venous Stasis Leg Ulcers

Venous Stasis Ulcers

This study will demonstrate whether PEMF therapy is an effective adjunct treatment to the
traditional treatment protocol used for the resolution of VSLU and of the pain associated
with them. This is a 4 arm study done by comparing the outcomes of treatment with a
low-power PEMF device, a medium-power PEMF device and a high-power PEMF device against
those obtained from the control group treated with a sham PEMF device.

A device usability study is included in the study protocol to evaluate the participants'
understanding of the device packaging, the User Manual, the device labeling, the controls
and the directions for use. An un-blinded assistant ("UA") will manage the device
usability study and hand out all informational literature and instructions to each
participant, in accordance with the randomization protocol. Participants' success will be
rated and their perception on the ease of use and how to make the device easier to use
will be solicited.

Safety precautions and contraindications are specifically defined, and adverse/
unexpected events and reactions, if any, will be documented as they arise.

The primary aims of the study are to assess the effects of 16 weeks of PEMF treatment on
the VSLU with one of three PEMF devices of different power levels against a sham PEMF
device. The study has 3 specific aims:

Aim 1 (Primary) Determine if the use of specific PEMFs affect the time for healing
trajectory of VSLU. Healing trajectory over the 16 week of the study protocol will be
measured as the area under the curve for total lesion area expressed as a percentage of
the baseline area.

Aim 2 (Secondary) Determine if VSLU and serum levels of three inflammatory cytokines:
IL-1, IL-6 and TNF-alpha are affected by the use of specific PEMFs.

Aim 3 (Secondary) Determine if VSLU pain is improved by the use of specific PEMFs. Pain
levels will be assessed with the use of allowed pain medication use by each participant.
Pain will also be assessed with the five (5) pain scales from the National Initiative on
Pain Control pain assessment scales ("NIPC scales") that will help each participant
describe his/her pain levels and characteristics both quantitatively and qualitatively.

Eighty participants will be enrolled on the basis of leg ulcers due to venous
insufficiency (VSLU) alone unless there are exclusions factors. The 80 participants will
be divided in four groups of 20 participants: three treatment groups and a control group.
Of the initial 80 participants at the investigation site approved to participate in this
study, the outcome data of a net total of 72 participants, 18 per group, will be
considered for analysis. The randomization protocol used for this study will occur in two
stages: first with the blinding of the participants and the random assignment of a unique
record number ("URN") to each of them and, second, with the random allocation of one of
the PEMF or sham devices to each participant. Device allocation will be done according to
a computer-generated table of random permutations designed to balance the number of
participants in each group. All the data from the follow-ups, various assessments and
testing procedures will be collected under the study URN for each participant. The URNs
will be kept in a URN Record Log and kept in a locked cabinet in the principal
investigator ("PI") 's office. Aside from the UA who will not be involved in data
collection, monitoring or analysis, the investigators will be blinded to the URN
assignment and to the PEMF or sham treatment protocol followed by each participant during
the study. The randomization will not be broken until all eighty participants have
completed the study.

The required effect sizes are all large; however, the PEMF effects are expected to be
very large. The sample size of 80 participants provides required large effect sizes.
Twenty patients will be enrolled per group and 18 are expected to have enough data to be
included in the analysis.

Aim 1 With 20 participants enrolled in each of four arms, and a net sample size of 18 per
group (accounting for 10% with incomplete data) and a p-value of 0.017 required for
significance, there will be 80% power for a t-test to detect an effect size of 1.1 (i.e.
a difference in mean area under the curve equal to 1.1 standard deviations). The
secondary analysis for time to complete healing will have 80% power to detect a hazard
ratio of 3.0.

Aim 2 and 3 The power for the multivariate test will be approximated by that available
for a two sample t-test. With a net sample size of 18 per group and a p-value of 0.017
required for significance, the effect size will need to be 1.1 in order to have 80% power
for a t-test. For the Wilcoxon rank sum test, the effect size may be expressed by the
quantity Prob(X < Y) where X and Y are drug usage values from a random control group
patient and a random patient from one of the PEMF groups. Under the null hypothesis,
Prob(X < Y) = 0.5. With a sample size of 18 per group and alpha = 0.017, there will be
80% power to detect Prob(X < Y) = 0.81.

The Project Director, a direct agent of the company sponsoring the study, will
periodically visit the research site to ensure the study is conducted in compliance with
the approved Clinical Investigation Protocol and that the PI, the research assistant
("RA") and the UA adhere to the Protocol.

A record of the number of all screened participants, participants who refuse entry, and
those entered in the study will be kept by the UA to follow CONSORT guidelines. He or she
will also be informed and keep a record of any dropouts and the reason the participant
was dropped from the study.

Statistical data will include 2 series of survey questionnaires at baseline and at the
end of the study. The questionnaires include: Your Health in General (SF-36) and pain
assessment using the National Initiative on Pain Control pain ("NIPC") assessment scales.
A count, measurement and imaging of the VSLU using Silhouette High Tech cameras. Pain
levels and pain medication intake will also be obtained weekly using a Caregiver Diary. A
fluid and a small blood sample will be collected weekly from the VSLU area and tested for
various inflammation biomarkers and growth factors. The data will be noted using a series
of case report forms.

The primary tests for a PEMF benefit will be made using a Hochberg adjustment to take
into account testing a single primary outcome measure (healing trajectory) measured three
times, once for each of three different PEMF variations versus control. Under the
Hochberg method, if all three primary test p-values are under 0.05, then all three will
be considered significant. However, if only one is under 0.05, it will need to be under
0.05/3 = 0.017 in order to be considered significant. Assuming at least one of the PEMF
variations is superior to control for at least one of the outcomes, a secondary analysis
will compare each of the PEMF variations to the other two. A Hochberg adjustment will
also be made for each of the two sets of secondary comparisons (pain and cytokines).

Aim 1 (Primary) The healing trajectory over 16 weeks will be compared for each PEMF
variation versus the control group by t-test. Healing trajectory will be measured as the
area under the curve for total lesion area expressed as a percentage of the baseline
area.

Secondary analysis will use a log rank test to compare the times to complete healing.
Descriptive analysis will plot the number of ulcers and their combined area over time for
each subject. Kaplan-Meier survival curves for the time to complete healing will also be
produced.

Aim 2 (Secondary) A multivariate test will be made comparing each PEMF group versus
control, for a vector made up of the three cytokines: IL-1, IL-6 and TNF-alpha.

Aim 3 (Secondary) A multivariate test will be made comparing each PEMF group versus
control, for a vector made up of the five pain scales. Pain medication usage will also be
summarized using two quantities: a morphine equivalent dose to summarize all opioid drugs
used, and a maximum dose equivalent for NSAIDs. Averages for these two medication use
measures will be computed for the 16 weeks of observations and each will be analyzed
separately using a Wilcoxon rank sum test.

The blinding assessment will occur at the end of the treatment protocol. Participants and
investigators will be probed as to the device and treatment protocol each received.

All data, resulting analyses, and reports will remain proprietary to the sponsor. All
case report forms and final data reports will be submitted to the sponsor for review and
approval prior to any publication being made.

The data obtained from this study will demonstrate whether treatment with specific PEMFs
affect the time for healing trajectory of VSLU; affect VSLU and serum levels of
inflammatory cytokines; and if VSLU pain is improved.

A successful resolution of leg ulcers from venous stasis and the associated pain using
therapeutic means, such as PEMF therapy, that are conservative, non-invasive,
non-pharmacological and with no known undesirable side effects may prove to be quite
significant.

PEMF therapy with a high-power PEMF device

PEMF therapy with a medium PEMF power device

PEMF therapy with a low-power PEMF device

PEMF therapy with the sham PEMF device

A Sham Controlled Study to Compare the Effectiveness of Three Different Power Levels of PEMF Devices in the Treatment and Resolution of Venous Stasis Leg Ulcers

The healing trajectory will be evaluated after 16 weeks of PEMF treatment with one of
three PEMF devices of different power level or a sham device. Leg ulcer area will be
documented and a healing timeline will be defined. If healing is complete prior to the
end of the 16-week treatment protocol, the RA will compile the length of time required
for healing.

The assessments will be evaluated after 16 weeks of PEMF treatment with one of three PEMF
devices of different power level or a sham device. A fluid sample will be taken from the
ulcer and a blood sample will be obtained from the participant. Both samples will be spun
and placed at -70 degrees C. Serum and blood analyses will include a cytokine panel with
IL-1, IL-6 and TNF-α. The following biomarkers: Transforming Growth Factor ("TGF") ,
Vascular Endothelial Growth Factor ("VEGF"), pro-inflammatory cytokines including IL-1
and IL-6, and Matrix Metalloroteinase ("MMP"), MMP-9 and MMP-13 will also be compared.

The study will be terminated for each participant upon the healing of the venous leg
ulcer(s) or at 16 weeks upon completion of the study, whichever comes first.

Pain levels will be recorded weekly and evaluated after 16 weeks of PEMF treatment within
one of three PEMF devices of different power level or a sham device. Pain medication
intake records from a Caregiver Diary and weekly follow-up medical examinations that will
include an evaluation of pain using the National Initiative on Pain Control pain
assessment scales (NIPC scales) will be collected and analyzed.

20 participants with VSLU will receive PEMF therapy with a high-power PEMF device for 10
minutes twice a day for each VSLU area.

20 participants with VSLU will receive PEMF therapy with a medium-power PEMF device for
15 minutes twice a day per VSLU area.

20 participants with VSLU will receive PEMF therapy with a low-power PEMF device for 30
minutes twice a day per VSLU area..

20 participants with VSLU will receive PEMF therapy with a sham PEMF device identical to
the low-power PEMF device and will treat each VSLU area for 15 minutes twice a day.

The Effects of Pulsed Elelectro-Magnetic Fields ("PEMF") in the Treatment of Venous Stasis Leg Ulcers

About this trial

Study ID

Status

Type

Placebo

Accepting

Not accepting

Trial Timing

What is this trial about?

What are the participation requirements?

Locations

Location

Status