Surface Stimulation for Female Sexual Dysfunction
Phase: NA
Conditions: Female Sexual Dysfunction
Sponsor: Timothy Bruns

 
 
Surface Stimulation for Female Sexual Dysfunction 
NCT02692417 
Study Protocol 
October 15, 2016 
 
 

Research Design and Methodology 
Design overview 
We have planned a randomized pilot study to evaluate the use of two skin-surface electrical 
stimulation approaches for improving sexual arousal. Subjects will be assigned one of two stimulation 
approaches and will receive the experimental treatment during a twelve-week test period. Standard 
sexual function and quality of life surveys will be completed at key time points to evaluate the effects 
of the experimental stimulation as compared to before study initiation and to look for any long-term 
residual effect. Participants will also be given a demographics questionnaire once during the study, so 
that we can evaluate possible stratification among participants and stimulation responders. 
 
Description of methods and analysis 
Patients will be randomly assigned to one of two study groups: receiving DGNS or PTNS. In this 
pilot study, as has been standard for prior pilot evaluations of DGNS and PTNS [1-5], we will not have 
a control stimulation paradigm that does not activate the nerves of interest. While this control 
stimulation is desired for an ultimate demonstration of this approach, its design will be outside the 
scope of what is feasible with these pilot funds. To date there has only been a single controlled 
evaluation of PTNS which also included a control stimulation paradigm [6]. We plan to emulate that 
approach after demonstrating feasibility here. See Figure 1 for the study paradigm.  
For subjects assigned to the dorsal genital nerve stimulation test group, electrodes will be placed 
as in Figure 2. Electrodes will be standard TENS skin-surface electrodes that are 2 cm in diameter. 
Test electrodes will be placed on either lateral side of the clitoris, with not more than 5 mm to each 
electrode edge, with cathode indifferent. At the first stimulation session, the pudenda-anal threshold 
(PAT) for driving reflex closure of the anal sphincter will be determined by starting with a 5 mA, 1 Hz 
stimuli through the test electrodes and increasing in 5 mA steps until sphincter closure is observed. 
Thereafter, test stimulation will be applied at 20 Hz and 2 x PAT or below a level at which the subject 
notes discomfort, whichever is lower. The anticipated test amplitude is within 30 – 60 mA [7-9]. After 
placement of electrodes and draping of the region, stimulation will be applied for 30 minutes in each 
session. 
For subjects assigned to the posterior tibial nerve stimulation test group, the same electrodes as 
for DGNS will be placed as in Figure 3. The test electrodes will be placed just above the medial 
malleolus (cathode) and the ipsilateral calcaneus (anode). At the first stimulation session, the test 
electrode stimulation level will be determined with 1 Hz stimulation at 5 mA and increased in 5 mA 
levels until a rhythmic flexion of the toes is observed or the patient notes discomfort. Thereafter the 
test stimulation will be a level just below that at which the motor or discomfort responses occurred [2]. 
After placement of electrodes and draping of the region, the appropriate stimulation will be applied for 
30 minutes in each session. Dr. Berger will place the electrodes on subjects at each appointment. 
Stimulation effects on sexual arousal are unlikely to be observed in the clinic. If this study is 
successful, future proposals to investigate underlying mechanisms may evaluate in vivo effects with 
animal models. We will have subjects complete four standard surveys as has been done for other 
 
Figure 1. Study paradigm. Subjects will be randomized into one of two test groups 
(DGNS/PTNS). Sexual Function and Quality of Life surveys will be taken at study initiation 
and at 6-week intervals afterwards. The final 6-week period of no stimulation will look for 
long-term carry over. 
DGNS:
DGNS Active
DGNS Active
No Stim
PTNS:
PTNS Active
PTNS Active
No Stim
- Survey
Group
6 weeks
6 weeks
6 weeks
N
10
10

neuromodulation studies [1], [6], [10-12]. The Female Sexual Function Index (FSFI) is a standardized 
survey with 19 questions on sexual health that provides a maximum score of 36 [13] (See Appendix 1 
for survey). The short form 36-question (SF-36) quality of life survey was designed for general use in 
clinical practice [14] and will be used here to assess overall impact (See Appendix 2 for survey). The 
Measure of Symptoms - American Urological Association Symptom Index is a standardized 8-
question survey assessing urologic concerns. The Patients’ Global Impression of Change (PGIC) 
Scale is a 1-question survey designed to assess patients’ feelings of improvement after intervention. 
Subjects will take the four surveys before study initiation (baseline), after each of concurrent 6-week 
stimulation sessions in the clinic (6weeks; 12weeks), and six weeks after study completion (long-
term).  
Due to the relatively small sample sizes planned for this study, we will use non-parametric 
statistical testing. We will use a two-sided Wilcoxon rank sum test to make comparisons of the survey 
scores among the different subject groups [1], [6], [8], [15], with a significance level of 0.05. FSFI and 
SF-36 scores will be compared for each of the potential comparisons among the baseline, 6-week 
and 12-week study time points and at long-term time point, for DGNS and PTNS groups separately.  
We plan for a total study size of 30 subjects. 15 
subjects will be assigned to each stimulation group – 
DGNS and PTNS. As this is a pilot study that has not 
been performed before, we do not have an effect size 
from which to calculate a target sample size. This study 
size of 15 subjects for each stimulation approach was 
selected for two reasons. Our primary factor was that prior 
pilot studies using these stimulation approaches for other 
patient groups used similar study sizes of 9-10 subjects 
[3-4], [8-9]. Our secondary factor was that given the one-
year time frame of our planned study, larger sample sizes 
may not be feasible. If one or both stimulation approaches 
are successful, larger sample sizes will be performed in 
subsequent studies. 
 
Potential difficulties 
We anticipate several potential difficulties with these 
planned studies. Patient compliance may be an issue, as 
the need to visit the clinic for 12 consecutive weeks may 
be a burden. We may adjust the study budget (or draw 
from Dr. Bruns’ startup funds) to allocate funds to pay for 
daily parking (~$7) and to give a lump 
sum upon completion of the study ($50) to 
each subject. As other PTNS studies use 
weekly study durations, sometimes with 
much larger sample sizes, we expect that 
a similar willingness will occur here. 
It is possible that patients find the 
planned stimulation amplitudes (e.g. PAT 
or 2 x PAT) to be uncomfortable. As it is 
not our goal to explore optimal stimulation 
parameters here, we will keep current 
levels as low as necessary to maintain 
subject comfort.  
It is possible that transient genital 
arousal or pain may occur in the clinic 
directly as a result of the applied electrical 
 
Figure 3. Electrode setup for PTNS. For experimental 
PTNS, the TENS unit will be connected to electrodes, 
on either side of the ankle. Figure modified from [6]. 
 
Figure 2. DGNS electrode locations. 
For experimental DGNS, the TENS 
unit will be connected to electrodes 
placed on either side of the clitoris. 

stimulation. To protect subject privacy and modesty, we will ensure that subjects are located in 
private rooms and left alone for the duration of applied stimulation. Subjects will be given a method to 
report uncomfortable side effects if they should occur. At the conclusion of each session, we will 
survey subjects as to any transient pain or arousal to compare effects over time. 
It is possible that patients attending Dr. Berger’s clinic do not have intercourse frequently enough 
to be eligible for the study ( 1 time per month). If we observe that occurrence through the first month 
of recruitment (3 clinics) then we will relax the criteria to be a desire to have intercourse several times 
per month. Conversely, it is possible that subjects who have intercourse 1-2 times a month may not 
provide sufficient perspective on the efficacy of the stimulation for improving arousal. We will observe 
for this potential trend during the first 5-10 patients and will adjust the inclusion criteria threshold 
upwards as necessary. 
It is possible that patients may develop psychological discomfort during the research intervention. 
To reduce this risk, patients will be fully informed about the treatment regimen, such as the fact that 
they may have a doctor placing leads on their genitals every week. They will also be reminded that 
their continued participation is voluntary. If psychological trauma is raised, patients will be referred to 
our sexual health therapists for treatment.  Casey O'Gara is a registered nurse and sexual health 
therapist who does such therapy and is part of the study team. 
 
Collection, analysis and interpretation of results 
Each study subject will be assigned an identification number. Only this number will be used to 
identify subjects in any individual tabulation. It is expected that only group data will be published. If 
individual subject data is to be published, no identifying information will be included. The study files 
will be maintained in a secure location. Access to computerized data will be restricted to IRB-
approved study personnel. Password authorization will be enforced. 
The study coordinator or other research team staff will provide both the FSFI and the SF-36 
surveys to each subject, in paper form, upon their initiation into the study. Subjects will be given up to 
an hour to complete the survey by circling their responses on the paper form. The form for each 
subject will have the identification number as the only identifying piece of information on it. This same 
sequence will be performed at the other data collection points – after 6 weeks of testing (in the clinic 
before the 7th stimulation session) and after the 12th session. For the 6-week post-trial follow-up, a 
research staff will contact each subject to complete the survey over the phone, or will allow the 
subject to complete the survey and mail back in if they will not be visiting the clinic during that time. 
As described in the appendices, each survey has a scoring method that yields a total quality of life 
score and a total sexual satisfaction score. These scores will be compared across the different time 
points as discussed above. The study team will meet with a statistical consultant (UM Center for 
Statistical Consulting and Research) to confirm correct approaches and conclusions. The study team 
will also compare the results found to other reported studies in the literature that used similar 
methods and analysis approaches for consistency. As described in the appendices, each survey has 
sub-sections that we may compare individually, if the data suggests any sub-section trends. 
Data collection will be limited to the investigators and the research staff. All study personnel who 
have access to the data will be educated regarding the need to protect confidentiality and the 
procedure to be followed to ensure such protection. All staff will also be required to sign a standard 
medical record confidentiality agreement. 
 
Description of any new methods and why an improvement 
Currently there are no neuromodulation therapies available to address sexual arousal. Our 
approach of translating an approach validated for other pelvic organs represents a new direction in 
this field. Furthermore, these periodic clinic stimulation sessions, if efficacious, may lead to novel non-
regular sessions that reduce the load on patients or potentially to small minimalist implants that 
provide more user control. Either of these approaches would represent a novel approach in the field. 

Recruitment & Retention Plan 
Population characteristics  
The proposal involves a 30-subject prospective study of surface electrode stimulation (dorsal 
genital nerve or posterior tibial nerve) weekly sessions for improving sexual arousal. As described 
below, adult women over the age of 18 who are neurologically stable and have intercourse at least 
once a month will be candidates. Typical patients will likely be in excess of 40 years of age. During 
each stimulation session, subjects will be reclined in a chair or examination table and will have 
electrodes placed at the appropriate location. After setting of parameters, stimulation will be applied 
for 30 minutes in duration. 
We will be recruiting patients primarily from Dr. Berger’s pelvic pain clinic as described below. The 
characteristics of the patients include dyspareunia (pain with intercourse), and/or pelvic or bladder 
pain. The bulk of Dr. Berger’s pain in this clinic (~5 new patients each session, plus similar numbers 
of return visits) have pain with intercourse and pelvic pain as major components of their complaints. 
There is a sexual health therapist present in the clinic who sees most of the new patients, so we will 
have a psychosocial evaluation for many of them. 
Patients will also be recruited from the OB/GYN clinic, other sex therapists’ clinics, and UHS. 
 
Sampling plan  
We will seek patients who meet the study inclusion and exclusion criteria. Due to the relative short 
timeframe of this study length, we will not perform any random sampling of potentially eligible patients 
and will approach each candidate on a first come first serve system. There are no ethnic distributions 
of targeted/planned enrollment.  
 
Inclusion criteria 
 Adult women  18 years of age 
 Sexually active  1 time per month ( 2 times per month preferred) 
 Having sexual dysfunction as identified by a score of 19 or less on the FSFI-6 [16]. 
For each question: Over the past four weeks… 
How would you rate your level 
(degree) of sexual desire? 
Very 
high (5) 
High 
(4) 
Mod-
erate 
(3) 
Low (2) 
Very 
low or 
none at 
all (1) 
How would you rate 
your level of sexual 
arousal (“turn on”) 
during sexual activity or 
intercourse? 
No 
sexual 
activity 
(0) 
Very 
high (5) 
High 
(4) 
Mod-
erate 
(3) 
Low (2) 
Very 
low or 
none at 
all (1) 
How often did you 
become lubricated 
(“wet”) during sexual 
activity or intercourse? 
No 
sexual 
activity 
(0) 
Almost 
always 
or 
always 
(5) 
Most 
times 
(4) 
Some-
times 
(3) 
A few 
times 
(2) 
Almost 
never or 
never 
(1) 
When you had sexual 
stimulation or 
intercourse, how often 
did you reach orgasm? 
No 
sexual 
activity 
(0) 
Almost 
always 
or 
always 
(5) 
Most 
times 
(4) 
Some-
times 
(3) 
A few 
times 
(2) 
Almost 
never or 
never 
(1) 

How satisfied have you been with 
your overall sexual life? 
Very 
satisfie
d (5) 
Mod-
eratel
y 
satis-
fied 
(4) 
About 
equally 
satisfie
d and 
dissatis
-fied (3) 
Mod-
erately 
dissatis
-fied (2) 
Very 
dissatis-
fied (1) 
How often did you 
experience discomfort 
or pain during vaginal 
penetration? 
Did not 
attempt 
inter-
course 
(0) 
Almost 
never 
or 
never 
(5) 
A few 
times 
(4) 
Some-
times 
(3) 
Most 
times 
(2) 
Almost 
always 
or 
always 
(1) 
 Neurologically stable 
 Ambulatory 
 Capable of giving informed consent 
 English speaking 
 Capable and willing to follow study procedures 
 
Exclusion criteria 
 Pregnant or planning to get pregnant during the study period 
 Clinically diagnosed neurological bladder dysfunction 
 Prior experience with PTNS or DGNS 
 Use of TENS on pelvis, back or legs 
 Implanted pacemaker, defibrillator, spinal cord stimulator, or sacral root stimulator 
 Vaginal infection 
 Coagulation disorders 
 Taking any investigational drug 
 
Recruitment and retention  
Potential subjects will be recruited from an investigator’s clinic or related clinics. Only 
inclusion/exclusion criteria that are provided by the patient as part of their check-in procedures or 
prior visits will be used to make a decision to approach a potential study subject. If a patient 
expresses interest in the study, then eligibility based on the full inclusion/exclusion criteria list will be 
verified.  
The study coordinator/nurse will follow up with the patient to schedule the stimulation sessions 
and will administer the baseline surveys (American Urological Association Symptom Index - AUA, 
Female Sexual Function Index – FSFI, Short Form Health Survey – SF-36) via mail or email. 
Informed consent will be obtained in person at the first stimulation session, prior to any intervention. 
After each session, the coordinator will remind subjects of subsequent meetings. 
Patient personal information will be protected per HIPAA guidelines. 
 
Plan for recruitment, informed consent process 
Eligible subjects will be identified through the treating physicians, and will be recruited in clinic by 
a study coordinator or team member. Dr. Berger has a pain clinic on the 1st, 3rd, and 5th Tuesday 
afternoon of each month at the Von Voigtlander clinic that is called the Female Pelvic and Urinary 
Pain clinic. Dr. Berger runs this clinic with Dr. Ann Oldendorf from Urology. In addition, Dr. Berger and 
his partners have general urogynecology clinics at which subjects could be recruited. 
Prior to the initiation of the study, an IRB approval for the study of human subjects will be 
obtained. The consent form will include all of the elements required by the FDA and state, local, and 
institutional regulations. Comprehensive written consent will be obtained from subjects prior to 
participation. A study coordinator or investigator will approach subjects to obtain informed consent. 

Open, witnessed and non-coercive discussion will be undertaken prior to signing of the consent 
document. 
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