A Randomized Controlled Crossover Study to Determine the Effectiveness of Peri-Neural Electrical Dry Needling (PNED) vs. Standard Care for the Treatment of Patients With Migraine Headaches
Phase: NA
Conditions: Migraine Headache
Sponsor: Wheaton Franciscan Healthcare

Protocol 
 
Perineural Electrical Dry Needling Migraine Treatment Study 
 
 
 
NCT: number not yet assigned. 
 
 
 
Upload to Clinicaltrials.gov date: January 29, 2020 
 
Last revised date: January 24, 2020 
 
 
 
 
 
 
 
PRINCIPAL INVESTIGATOR:
Dr. Joe Tepp PT Cert DN. 
Rehabilitation 
             ​(414) 389-3023 
                                                                  ​joseph.tepp@ascension.org 
 
 
 
 
 
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Table of Contents 
 
Study Summary
3 
Purpose and Objectives
4 
Background
4 
relevant preliminary data.
4 
Study Endpoints
4 
Study Intervention/Investigational Agent
4 
Procedures Involved
5 
Sharing of Results with Subjects
6 
Study Timelines
6 
Inclusion and Exclusion Criteria
6 
Local Number of Subjects
6 
Recruitment Methods
7 
Withdrawal of Subjects
7 
Risks to Subjects
7 
Potential Benefits to Subjects
8 
Data Analysis
9 
Data Management and Confidentiality
9 
Provisions to Monitor the Data to Ensure the Safety of Subjects
10 
Provisions to Protect the Privacy Interests of Subjects
10 
Economic Burden to Subjects
11 
Consent Process
11 
Process to Document Consent in Writing
11 
Setting
11 
Resources Available
12 
References
12 
 
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1.0
Study Summary 
 
Study Short Title/ Number 
PNED for migraine headaches 
Study Title 
A Randomized Controlled Crossover study to Determine the 
Effectiveness of Peri-Neural Electrical Dry Needling (PNED) vs. 
Standard Care for the Treatment of Patients With Migraine 
Headaches.  
 
Study Design 
Random controlled cross over trial 
Primary Objective 
Determine the validity and treatment effectiveness of PNED for 
patients with migraine headaches 
Secondary Objective(s) 
Determine the affects of PNED for migraine headaches for patients 
who are and are not on a CGRP antagonist drug 
Research Intervention(s)/ 
Investigational Agent(s)  
Perineural electrical dry needling.  
Study Population 
Individuals in the community with migraine headaches. 
Sample Size 
30 individuals 
Study Duration for 
individual participants 
A total of 5 weeks (2 weeks of treatment,  1 week wash out period, 
2 weeks of treatment)  
Study Specific 
Abbreviations/ Definitions  
PNED (perineural electrical dry needling) 
 
 
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2.0
Purpose and Objectives 
2.1
The purpose of this study is to improve care and outcomes for patients with 
migraine headaches. It will help to offer patients non-pharmacological 
management of their migraine headaches and/or offer an option for those 
looking to decrease their current dosage of medication.  
2.2
PNED will result in a decrease of reported pain intensity and frequency of 
patients with migraines.  
3.0
Background 
From current understanding of migraine pathophysiology, we know that it involves 
excitability of the trigeminovascular system.  Intercranial vasculature containing nociceptor 
innervation consists of unmyelinated (c-fibers) and thinly myelinated (a-delta fibers ) axons 
which hold vasoactive neuropeptides including substance P and calcitonin gene related peptide 
(GGRP).    When a migraine occurs, there is a cortical spreading depolarization, which on a 
molecular level involves a release of ATP, glutamate, potassium, hydrogen ions, glia or vascular 
cells, and CGRP and nitric oxide by activated perivascular nerves. These substances, including 
CGRP diffuse to come in contact with nociceptors causing neurogenic inflammation 
(vasodialation), thus propagating a headache.   
 
relevant preliminary data. 
3.1
Electrical perineural dry needling causes the release of substance-P and CGRG 
predominantly from non-neural structures, facilitating a negative feedback loop 
to neural and neuroactive components of the target tissue. This causes a 
lowering of the levels of CGRP which in turn decreases the inflammatory 
component thought to play a role in migraine headaches.   
 
Other studies have looked into other electro-analgesic treatments of both 
transcutaneous and percutaneous methods.  Both types providing promising results in 
regards to decreased headache pain.  This study seeks to investigate a specific protocol of 
PNED and its effects on migraine headaches.  
 
4.0
Study Endpoints 
4.1
This study will conclude once all 30 patients have been treated for 5 weeks.  
4.2
While there is no secondary safety outcome identified, a secondary outcome of 
the study will include an analysis of whether the purposed treatment protocol 
differed from those patients who are and who are not currently taking a CGRP 
antagonist drug.  
5.0
Study Intervention/Investigational Agent 
5.1
This study aims at investigating a treatment protocol. ​The device used is not 
investigational and currently in use as a treatment in physical therapy.​  It involves 
use of an ES-130 by ITO (Japan) using a DC 9V battery producing an asymmetrical 
biphasic waveform. The unit has 6 available leads with alligator clamps, 
connecting to monofilament dry needle shafts of 15 or 30 mm length, 0.25 mm 
diameter. 
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11.0 Recruitment Methods 
11.1 Study subjects will be accessed either via health care provider referral from 
physicians, physician assistants, nurse practitioners, dentists, optometrists, 
physical therapists or from patient to patient referrals.  Potential Participants 
may also be contacted by flyers, information sheets, or over the phone. ​Most 
subjects will be identified from patients the PI will be treating or has treated in 
the past. The PI will present the study to possible subjects in person or possibly 
contact by phone. In addition, colleagues may refer possible subjects by 
presenting the study verbally or using the flyer and the PIs contact information. If 
they agree to be contacted, the PI may contact them to follow up. 
 
           The PI will determine general eligibility before presenting the full study 
            to subjects. Most information will be known to the PI if he is treating the 
           patient, or is available in the EMR. Some questions may be asked (see 
           attached) but responses will not be recorded.  
 
11.2 The source of patients will be patients at the clinical site 
11.3 Potential subjects will be identified via clinician referral or based off of the initial 
           evaluation/appointment as a physical therapy patient, if being seen via direct  
           access and not referral.  
11.4 Recruitment materials attached as part of the IRB application.  
12.0 Withdrawal of Subjects 
12.1 Subjects will be withdrawn from research without their consent if 1.  It is deemed 
medically necessary and in the best interest of the patient and 2. If the subject is 
non-compliant with the study, including but not limited to: no showing to 3 or 
more appointments.  
12.2 There is no procedure for termination.  Participants will have the option to 
remain as patients and continue to receive treatment.  
12.3 If a subject decides to withdraw from the research, all data collected concerning 
that subject will be promptly terminated.  
13.0 Risks to Subjects 
13.1 List the reasonably foreseeable risks, discomforts, hazards, or inconveniences to 
the subjects related the subjects’ participation in the research. Include as may be 
useful for the IRB’s consideration, a description of the probability, magnitude, 
duration, and reversibility of the risks. Consider physical, psychological, social, 
legal, and economic risks. 
Risks may include the following: 1. Pain or discomfort, 2. Needle break, 3.Medulla 
oblongata puncture, 4. Vaso-vagal response “needle shock” or fainting, 5. 
Infection.  
In regard to the risks mentioned above:  
Pain associated with using the ES-130 device will be minimized with slowly  
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ramping the intensity of electric impulse to be within the patients comfort level 
while observing the patient’s verbal and non-verbal response. 
 (moderate-low probability) 
A needle break will be avoided by using high quality needles and not autoclaving  
reusable needles.  The needles used are seirin brand needles which are sterilized  
and individually sheathed.  
(low probability) 
 
Medulla oblongata puncture will be avoided by utilizing proper techniques in the  
procedure of dry needling and proper sized needles per above.  The primary  
investigator who is performing the treatments is certified by the Dry Needling  
Institute and has 5+ years experience with DN.  
(low probability) 
A vaso-vagal response will be minimized with patients placed in a prone  side 
lying  or supine position and not seated when dry needled.  Signs of potential 
fainting following treatment will be observed: turning pale, weak pulse, feelings of 
being unwell, sweating, having a sense of giddiness, weakness, palpitations, 
nausea or vomiting will be monitored.  Precautions will be made to avoid causing 
a fainting response by making sure the patient is not overly anxious, hungry 
(especially if diabetic) or fatigued prior to the procedure.  If signs and symptoms 
appear, needles will be removed and the patient will lye supine with legs 
elevated.  
(low probability) 
Risk of infection will be reduced with the treatment provider utilizing proper  
hand washing prior to performing the procedure, wearing gloves and using an  
alcohol wipe to cleanse the treatment area.   
 
(low probability) 
 
*It should be known, again, that this treatment is currently in use in physical therapy and 
not experimental.  This study is set to identify whether the protocol for 
treatment is valid and effective for patients with migraine headaches.  
 
13.2 Aside from those mentioned above, no unforeseeable risks are identified.  
13.3 Dry needling is contraindicated when pregnant.  Subjects will not be included if 
they are pregnant or trying to become pregnant.  
13.4 There will be no risks to anyone who is not a subject.  
14.0 Potential Benefits to Subjects 
14.1 This crossover study will allow all patients to receive the experimental treatment 
and potentially benefits from reduced migraine pain and reduced frequency and 
intensity of headaches.  Based on the outcome observed from using the 
treatment protocol on current and past non study related patients there is a high 
probability of achieving a favorable result lasting anywhere from 1-6 months. 
 
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15.0 Data Analysis 
Null hypothesis: There will be no difference between treatment groups in regard to 
pain and neck disability rating including frequency and intensity of headaches.  Alpha 
will be set to 0.05 
   This will be a random controlled crossover study.  
We will use two different study periods that will each begin with a baseline 
assessment to compare the two different treatments.    Study subjects will have 
baseline assessments, then receive the treatment they were randomized to:   (the 
standard treatment arm or standard treatment and perineural electrical dry needle 
treatment arm) and then be assessed at the end of the two week treatment period 
to see if there has been a change in neck disability index or pain rating.  After a 1 
week washout period the study subjects will again have a baseline assessment of 
their pain and neck disability index and then crossover into the other study 
treatment arm for two weeks of treatment and again will be assessed at the end of 
the treatment period to see if there has been a change in neck disability index or 
pain rating.  
 
Primary Outcomes 
We will use the Wilcoxon Sign-rank test to determine if perineural electrical dry 
needles significantly improve pain when compared to standard treatment. A paired 
t-test will be done to determine if there is a significant improvement in the disability 
index following perineural electrical dry needle treatment when compared to 
standard treatment.  
Secondary Outcome 
Because this is a small trial it is unlikely that we will be able to determine if migraine 
drugs significantly modify the effect perineural electrical dry needle treatment has 
on pain and the neck disability index.   However we will look for any trends in 
interaction between perineural electrical dry needle treatment and migraine drugs 
using exploratory data analysis and box plot comparisons  
 
Assuming we recruit 30 study subjects, using a one-sided P value (0.025), the study 
will have power over 0.80 to detect a 50 % difference among treatment groups 
effects on the  neck disability index. 
 
16.0 Data Management and Confidentiality 
 
 
 
16.1 Each subject will have a corresponding data collection sheet which will be kept in 
a secure file cabinet.  The P.I will have access to this document.  As subjects will 
also be patients, data will also be made part of their chart using the EPIC 
documentation system.  
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16.2 Quality control of data will be done via the assistance of a data safety individual, 
Sara Kotchi, who will assist in the integrity and interpretation of the data via 
access to Carroll University’s statistical analysis capabilities.  
 
16.3 Describe how data or specimens will be handled study-wide: 
●
Data will include, whether the subject is currently taking a CGRP antagonist 
drug, frequency and intensity of headaches, neck disability index score and 
rating of pain.  
●
Data will be stored via paper collection sheet in a secure cabinet and via 
EPIC 
●
Data will be stored for the duration of the study. 
●
The P.I.  and research associate will have access to study data. Please note 
that once the research associate has the data, she will be blinded to the 
data, there will be no “identifiers” associated with any person.  
●
The P.I. is responsible for data transmission. 
●
Paper copies of data will be transmitted via in-person transfer.  
17.0 Provisions to Monitor the Data to Ensure the Safety of Subjects 
17.1 Describe​: 
Any adverse effect as part of this research will be documented in the patient’s 
chart in EPIC.   Any adverse effects will also be documented on the data 
collection sheets.  The research associate will have access to the data 
collection sheets and will assist in monitoring for adverse effects. Both the 
P.I. and research associate will communicate any adverse effects of this 
research to the IRB.  
●
Safety data and untoward events will be reviewed once per month. 
●
Safety information will be collected during study visits/patient treatment 
encounter. 
●
The data will be collected 2 days per week for 4 weeks with attention to 
safety beginning after the initial treatment.  
●
The P.I and research associate will review the data.  
●
Data will be reviewed 1 time per month.  
●
There is no current statistical test for analyzing potential harm to subjects.  
●
Conditions that trigger an immediate suspension of the research will 
include any noted harmful or adverse event that is a result of performing 
this research​.  
18.0 Provisions to Protect the Privacy Interests of Subjects 
 
18.1 Subjects in this study will be patients, thus privacy interests will be kept strictly to      a 
patient-provider relationship. 
18.2
Subjects will be “at ease” as he/she will be involved in this research as a patient.  There  will be 
no intrusiveness as subjects will be receiving treatment at a location, at a time and by a 
provider of their choosing.  
18.3
As subjects will be patients, the P.I. will have access to patient records via EPIC for any relevant 
data pertaining to their care.  
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19.0 Economic Burden to Subjects 
19.1 As patients, participants will be responsible for the cost of the treatment they 
receive in physical therapy.  
20.0 Consent Process 
20.1 Consent will be obtained.  Please refer to the consent form attached.  
●
Consent will take place in a private treatment room. 
●
As patients, subjects will have the option to “think It over” and discuss 
further any questions concerning consent at their next scheduled 
appointment. 
●
Regarding ongoing consent, Patients will be asked each treatment visit 
regarding whether they have any questions or concerns regarding this 
study.  
●
Whether you will be following “SOP: Informed Consent Process for 
Research (HRP-090).” If not, describe: 
o
Consent will be obtained by the P.I. 
o
The time devoted to a consent discussion may include, prior to a 
patient’s scheduled appointment, during the scheduled 
appointment, after a scheduled appointment.  
o
Steps that will be taken to minimize the possibility of coercion or 
undue influence, include a clear explanation of the voluntary nature 
of this study and the fact that the subject is able to receive the same 
care as the experimental group without being in the study.  
o
Time will be taken to clearly explain this study allowing for subjects 
to ask any questions that they might have as to make sure they 
clearly understand the study.  
Waiver or Alteration of Consent Process (consent will not be obtained, required 
information will not be disclosed, or the research involves deception) 
●
No waiver or alteration of consent will be made.  All patients will sign a 
consent form, attached to the IRB application. 
 
20.0 Process to Document Consent in Writing 
20.1 The consent form/template provided by the Ascension IRB will be used when 
obtaining consent.  
20..2 The consent form is attached to the IRB application 
 
21.0 Setting 
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1.2
Research will be conducted at a clinic located at 2500 West Layton Avenue, 
Milwaukee, WI. 53221 in the rehabilitation department in suite 160. 
●
Any patients who are receiving care, and or friends and family of patients 
in the clinic may be made known of this study.  
●
Research procedures will be provided in a private treatment room.  
●
No advisory board aside from the Ascension IRB will be involved in this 
study.  
22.0 Resources Available 
●
Subjects will be current patients with recruitment depending on clinician 
and or self-referral.  
●
Time devoted to this research will include that of working as a provider, 
approved time (2 hours per week) as this research is part of the Ascension 
Rehabilitation Master Clinician program and my own personal time. It is 
estimated that 4-6 hours per week will be devoted to this research.  
●
The facility is an outpatient clinic. 
●
In the building of which this research will take place, there is primary 
physician services.  The closest hospitals are St. Francis Hospital and 
Franklin Hospital.  
●
Prior to performing the actual research the P.I. and research associate will 
discuss the research procedures, duty and function.  
23.0 References 
 
 
●
Noseda Rodrigo, Burnstein Rami,  “Migraine pathophysiology: anatomy of the 
trigeminovascular pathway and associated neurological symptoms, CSD,sensitization and 
modulation of pain.” Pain. 2013 December ; 154 Suppl 1: . doi:10.1016/j.pain.2013.07.021. 
(published in the NIH). 
 
●
Erin N, Ulusoy O. Differentiation of neuronal from non-neuronal Substance P. Regul Pept. 
2009;152(1-3):108-113. 
 
●
Bullock CM, Kelly S. Calcitonin gene-related peptide receptor antagonists: beyond migraine 
pain–a possible analgesic strategy for osteoarthritis? Curr Pain Headache Rep. 2013;17(11):375.  
 
●
Raud J, Lundeberg T, Brodda-Jansen G, Theodorsson E, Hedqvist P. Potent anti-inflammatory 
action of calcitonin gene-related peptide. Biochem Biophys Res Commun. 
1991;180(3):1429-1435. 
 
●
Ahmed, hasham et al. Use of Percutaneous Electrical Nerve Stimulation (PENS)  
in the Short-term Management of Headache. ​Headache ​2000;40:311-315  
 
●
Russo, Antonio et al. Transcutaneous supraorbital neurostimulation in “de novo” patients 
with migraine without aura: the first Italian experience. The Journal of Headache and Pain 
(2015) 16:69 DOI 10.1186/s10194-015-0551-3  
 
 
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