Double-blind Phase 2 RCT: Effect of Acupuncture on Patient Vulvodynia Outcomes
Phase: NA
Conditions: Vulvodynia, Vulvodynia, Generalized, Vulvar Vestibulitis
Sponsor: University of Illinois at Chicago

Title: DOUBLEͲBLINDPHASE2RCT:EFFECTOFACUPUNCTUREONPATIENTVULVODYNIAOUTCOMES

RESEARCHPROTOCOL
Dated8/15/2017
 
 
1 
 
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
Investigators:

JudithSchlaeger,PhD,CNM,LacͲPrincipalInvestigator,UICCollegeofNursing
DianaJ.Wilkie,PhD,RN,FAAN–CoͲInvestigator,UICCollegeofNursing
AlanaSteffen,PhDͲCoͲInvestigator,UICCollegeofNursing
WilliamKobak,MDͲCoͲInvestigator,UICCollegeofNursing

BackgroundandPurpose:
OurlongͲtermgoalistodemonstratetheeffectsofacupunctureforthetreatmentofvulvodynia.Upto
14millionAmericanwomenhavevulvodynia,1,2adebilitatingpainsyndromecharacterizedbypain
(burning,irritation,stingingorrawness)inthevulvaanddyspareuniathatrenderssexualintercourse
virtuallyimpossible1,2andleavesthesewomendesperateforrelief.Notonlyarewomeninpain,but
theyoftenlosetheirpartnersorhaverelationshipdifficultiesduetotheirinabilitytohavesexual
intercourse.3,4Notherapieshavebeenprovenefficaciousandrapidpainreliefisunpredictableand
rarelypossible.1,2AfterexhaustingWesternMedicineoptions,thesewomenoftenturnto
acupuncture.1,2Butincontrasttootherpainconditions,6therehavebeennoacupunctureshamcontrol
studiesofvulvodynia.

Onlyfourstudies,includingoneofours,7providesomeevidenceoftheeffectofacupunctureon
vulvodynia.Inthree,singleͲgroupacupuncturestudies,womenhadlesspain,betterqualityoflife,
improvedsexualhealth,andimprovedmentalhealth.8–10OurrandomizedwaitͲlistcontrolledpilotstudy
of36womenwithvulvodyniashowedgreatpromise.Wefoundastatisticallysignificantandclinically
meaningfulreductioninvulvarpainanddyspareunia,andanincreaseinoverallsexualfunctionaftera
5Ͳweek,13Ͳneedle,10sessionacupunctureprotocol.7Thisnewlydeveloped,standardizedacupuncture
treatmentprotocol7isthefirstbreakthroughinthetreatmentofthispuzzlingdisorder.2Itincludes
acupuncturepointsthatrelievepaininthegenitals.Theresultsofourinitialpilotstudyprovidedthe
firstevidencefromatwoͲgroupdesignthattheacupunctureprotocolcouldreducepainintensity,pain
duringintercourse,andincreaseoverallsexualfunction.Ourfindings,however,warrantstronger
evidencetosupporttheinferencethattheeffectisindeedduetotheacupuncturesinceoursorno
otherstudyincludedashamcontrolorprovidedfollowͲupdatabeyondimmediateposttest,which
meansthatthedurationoftheacupunctureeffectisunknown.Ourrecentfeasibilitystudypavesthe
waytoovercomethisgapbyuseofdoubleͲblindacupunctureneedles.Findingsfromthesetwostudies
supportourproposalfortheworld’sfirstdoubleͲblindrandomizedcontrolledtrial(RCT)ofacupuncture
forvulvodyniawhileexploringitsdurationofeffect.

Wewillconductaphase2doubleͲblind,pretest/posttestRCTtocompareeffectsofpenetratingneedles
ortheskintouchplaceboneedlesonvulvarpaininour13Ͳneedle,10Ͳsessionacupuncturetreatment
protocol.Asampleofupto130women,withadiagnosisofvulvodynia,eithergeneralizedorprovoked
vestibulodynia,willberecruited.Subjectswillbestratifiedbytypeofvulvodynia,andwillbe
randomized1:1eithertothepenetratingneedlegrouportheskintouchplaceboneedlegroup.These
doubleͲblindneedleswillprovideastrongshamprocedure(placebo)tomaskboththeacupuncturist
andsubjecttothetypeofneedleusedforthe10Ͳtreatmentprotocol.


Title: DOUBLEͲBLINDPHASE2RCT:EFFECTOFACUPUNCTUREONPATIENTVULVODYNIAOUTCOMES

RESEARCHPROTOCOL
Dated8/15/2017
 
 
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Specificaimsareto:
Aim1.Comparethepenetratingneedlegroupandtheskintouchplaceboneedlegroupforeffectson
the:(a)primaryoutcome:vulvarpain(PAINReportIt®averagepainintensity,0Ͳ10),and(b)secondary
outcomes:dyspareunia(FSFIdyspareunia)andsexualfunction(FSFItotal).Wehypothesizethat
controllingforbaselinevalues,atposttesttherewillbestatisticallysignificantlessvulvarpain(primary)
anddyspareuniaandbettersexualfunctioninthepenetratingneedlegroupcomparedtotheskintouch
placebogroup.

Aim2.Insubjectswithaclinicallymeaningfulreductioninpainintensity(atleast1.5points)atposttest
comparedtopretest,describethedurationoftheacupuncturetreatmentandplaceboeffectsweekly
untilpainreturnstopretestorupto12weeksafterposttest.Wewilldescribethevariabilityovertime
invulvarpainintensity(0Ͳ10)afteratamponinsertionͲremovalstimulusandtherebyexplorethe
durationoftheeffectbyinterventiongroup,vulvodyniasubgroups,anddemographicsubgroups(e.g.,
age,race,occupation).Thesefindingswillprovideinsightstoguidefutureresearchoninitial
andmaintenanceacupunctureforvulvodynia.

References
1.HaefnerHK,CollinsME,DavisGD,etal.Thevulvodyniaguideline.JLowGenitTractDis.2005;9(1):40Ͳ
51.
2.StockdaleCK,LawsonHW.2013VulvodyniaGuidelineupdate.JLowGenitTractDis.2014;18(2):93Ͳ
100.doi:10.1097/LGT.0000000000000021.
3.BrottoLA,YongP,SmithKB,SadownikLA.Impactofamultidisciplinaryvulvodyniaprogramonsexual
functioninganddyspareunia.JSexMed.2015;12(1):238Ͳ247.doi:10.1111/jsm.12718.
4.BassonR.Therecurrentpainandsexualsequelaeofprovokedvestibulodynia:aperpetuatingcycle.J
SexMed.2012;9(8):2077Ͳ2092.doi:10.1111/j.1743Ͳ6109.2012.02803.x.
5.XieY,ShiL,XiongX,WuE,VeasleyC,DadeC.Economicburdenandqualityoflifeofvulvodyniainthe
UnitedStates.CurrMedResOpin.2012;28(4):601Ͳ608.doi:10.1185/03007995.2012.666963.
6.VickersAJ,CroninAM,MaschinoAC,etal.Acupunctureforchronicpain:individualpatientdatametaͲ
analysis.ArchInternMed.2012;172(19):1444Ͳ1453.doi:10.1001/archinternmed.2012.3654.
7.SchlaegerJM,XuN,MejtaCL,ParkCG,WilkieDJ.AcupuncturefortheTreatmentofVulvodynia:A
RandomizedWaitͲListControlledPilotStudy.JSexMed.2015:n/aͲn/a.doi:10.1111/jsm.12830.
8.PowellJ,WojnarowskaF.Acupunctureforvulvodynia.JRSocMed.1999;92(11):579Ͳ581.
9.DanielssonI,SjöbergI,OstmanC.Acupunctureforthetreatmentofvulvarvestibulitis:apilotstudy.
ActaObstetGynecolScand.2001;80(5):437Ͳ441.
10.CurranS,BrottoLA,FisherH,KnudsonG,CohenT.TheACTIVstudy:acupuncturetreatmentin
provokedvestibulodynia.JSexMed.2010;7(2Pt2):981Ͳ995.doi:10.1111/j.1743Ͳ6109.2009.01582.x.

Studydesign:
Wewillconductapretest/posttest,randomized,placebocontrolledphase2efficacystudyon130
subjectswithvulvodynia,withhighscientificrigor.Inthisadequatelypoweredstudy,wewillcompare
twogroups(penetratingacupunctureneedle[treatment]groupandskintouchneedle[placebo]group)
ina13Ͳneedle,10Ͳsessionacupunctureprotocoldeliveredtwice/weekfor5weeksforeffectsonvulvar
pain(primaryoutcome),anddyspareuniaandsexualfunction(secondaryoutcomes).Subjectswillbe
stratifiedbytypeofvulvodynia(generalizedorprovoked)andrandomized1:1eithertothepenetrating
needlegrouportheskintouchplaceboneedlegroup.ThesedoubleͲblindneedleswillprovideastrong

Title: DOUBLEͲBLINDPHASE2RCT:EFFECTOFACUPUNCTUREONPATIENTVULVODYNIAOUTCOMES

RESEARCHPROTOCOL
Dated8/15/2017
 
 
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shamproceduretomaskboththeacupuncturistandsubjecttothetypeofneedleused.The
acupuncturistwillbewellͲtrainedinthestudyprotocolandwillbeobservedforfidelity.Wewillobtain
measuresat2timepoints(baselineandimmediatelypost10thacupuncturetreatment[5weeks]).
Durationofeffectswillbemeasuredweeklybeginningoneweekafterposttestforupto12weeks.

Subjectidentification,recruitmentandconsent:
Thesubjectswillbewomenwithadiagnosisofvulvodynia,whoare18–45yearsofage.Potential
participantswillberecruitedfromclinicalandcommunitysettingsinChicago,suchastheUICcampus
andsurroundingcommunities,gynecologists,certifiednurseͲmidwives,familyphysicians,andwomen’s
healthphysicaltherapypractices.RecruitmentwillalsobeconductedviaalinkontheNational
VulvodyniaAssociation(NVA)website.WewillalsorecruitthroughsocialmedialikeFacebook,in
additiontothroughphonecallsandemails.Weplanonrecruitingupto130womentoensurethatwe
havefulldataon80subjectsafterscreeningandattrition.Wewillstrivetoenrollaraciallyand
ethnicallydiversesampleofwomen.

TheconsentprocesswillbecompletedattheUICCollegeofNursing.Itmayalsobecompletedat
anotherUICorotherprivatelocationchosenbythepotentialsubjecttogooverthedetailsofthestudy
andinformedconsent.AllstudyprocedureswillbeconductedattheUICCollegeofNursinginfully
equipped,clinicalresearchexamroomsonthesecondfloor.Thescreeninggynecologicalscreening
examwilltakeplaceinoneoftheexamroomsintheCONoratDr.Kobak’sofficeintheUIChospital.

Procedures:
Theresearchspecialist(RS)willdetermineinitialeligibilitybyscreeningpotentialparticipantsduringan
initialtelephoneorinͲpersoninterviewaccordingtotheinclusionandexclusioncriteria.Women
deemedtobeeligibleandinterestedinparticipatingwillbescheduledtogoovertheconsentprocess
andwillthenreceiveagynecologicalscreeningexambyDr.WilliamKobak,aurogynecologistwith
expertiseinchangesinpelvicfloortissuerelatedtovulvodynia,orDr.JudithSchlaeger,apracticing
certifiednurseͲmidwifewithover29yearsofexperienceandapracticingacupuncturistspecializingin
thetreatmentofvulvodyniapatientsfor15years.Thisexamwillconfirmthediagnosisandsubtypeof
vulvodynia(provokedorgeneralized).Potentialparticipantswillalsobeaskedtoinsertandremovea
tamponasastandardizedstimulustoprovokevulvodyniapainandwomenwillbeeligibleiftheyreport
apainlevelof4orhigher.WewillalwaysusearegularsizeTampax™tamponwithapplicatoraspartof
thestandardizedprocedure.Participantsdeterminedtobeineligibleaftertheabovestepswillnotbe
abletocontinuestudyparticipation.

Basedonthegynecologicalexamresults,participantswillbeassignedtothegeneralizedortothe
provokedvulvodyniagroup.Eligiblewomenwillbeabletostartthestudyproceduresimmediatelyorat
afuturevisit.Rightbeforethefirstacupuncturesessionandonceaweekbeforeanacupuncture
treatment,aurinepregnancytestwillbeadministered.Ifitispositive,thesubjectwillbediscontinued
fromthestudy.

Participantswillbeassignedatrandomtotheexperimentalgroup,whowillbetreatedwithpenetrating
needles,orthecontrolgroup,wheretheneedleshaveablunttipthatpinchesbutdoesnotpenetrate
theskin.Thespecialneedlesusedinthisstudyareinsideanopaqueinsertiontubesothatboththe
acupuncturistandparticipantremainblindtogroupassignment.Theactualacupunctureneedles,

Title: DOUBLEͲBLINDPHASE2RCT:EFFECTOFACUPUNCTUREONPATIENTVULVODYNIAOUTCOMES
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however,areregularneedlesusedinroutineacupuncture.Allparticipantswillbeinformedthatthey
willreceiveeitherrealorfakeacupunctureandtheywillnotbetoldwhatkindofneedlestheyare
receivinguntiltheycompletethedurationofeffectportionofthestudy.Participantsinthecontrol
groupwillbeoffered10freerealacupuncturesessionswithregular(notdoubleͲblind)acupuncture
needlesadministeredbyasecondacupuncturistaftertheendofthe17weeks.Thedoubleblindneedles
aremanufacturedbyDr.Takakura,theinventorofthedoubleblindacupunctureneedle,andwillbe
senttoussterilizedandpackagedtomaintainsterility.

Allparticipantswillreceive10acupuncturesession,twosessionsperweekoveranapproximately5
weekperiod.Eachsessionwilllastaboutonehour.Thefirstandlastsessionsonly,whereparticipants
willcompletethestudyquestionnaires,areexpectedtolastanadditional30Ͳ60minutes.Each
acupuncturetreatmentwillconsistof13acupuncturepoints,ofwhich12pointsspecificallytreat
problemswiththegenitals.Oncethe13needlesareinsertedorplacedontheskininthe13points,they
willremaininplacefor45minutes.TheRSwillremainwiththesubjectsduringthetreatmentsession.

AtpreͲtest,beforethefirstacupuncturesession,andatpostͲtest,afterthe10thacupuncturetreatment,
participantswillbeaskedtoinsertandremovearegularTampax™tamponwithapplicatorasa
standardizedpainstimulus,andwillcompletethethreestudymeasuresofvulvarpainandsexual
functiononacomputerortablet:

1) PAINReportIt®computerizedprogramtoassesspainintensityaswellascollectdemographics
andmedicationsinformation
2) FemaleSexualFunctionIndex(FSFI)toassessdyspareuniaandsexualfunction
3) VulvarPainFunctionalQuestionnairetodescribethephysicaldimensionofimpairmentin
womenwithvulvodynia
4) AtpostͲtest,participantswillalsocompletetheDoubleͲBlindNeedleQuestionnaireforthe
participantstoreportwhetherornottheyremainedblindedtothetypeofneedleused
(penetratingorskintouchplacebo).

Weeklyforupto12weeksafterthe10thtreatmentsession,thesubjectswillbeaskedtoinsertand
removearegularTampax™tamponwithapplicatorfromtheirvaginaandcompletetheweeklyvulvar
paindiarytorecordtheirvulvarpain,sothatwecandeterminethedurationofthetreatmenteffects.

Samplesize:
Weplantorecruit130womentoensurethatweobtainfulldatafor80subjects.

Anticipatedrisks:
Thisstudyhasminorrisks.Thereisasmallriskofmildbruising,sorenessorbleedingafterthereal
acupunctureneedleiswithdrawn.Thereisariskthatparticipantsmayexperienceanegativereaction
fromacupunctureandtherebyexperienceworsesymptomsfromparticipationinthestudy.Participants
mayfeelmilddiscomfortuponneedleinsertion,butthisdissipatesoncetheneedlehasbeeninserted.
Toavoidorminimizetheserisksonlyexperiencedlicensedacupuncturistswillperformtheacupuncture.
Thereisariskthatsomeofthequestionsinthequestionnairesmaymaketheparticipants
uncomfortable,nervousortired,buttheydon’tneedtoansweranyquestiontheydon’twishtoanswer.
Thereisalsotheriskoflossofprivacyorconfidentiality,butwewillavoidthisriskasmuchaspossible.

Title: DOUBLEͲBLINDPHASE2RCT:EFFECTOFACUPUNCTUREONPATIENTVULVODYNIAOUTCOMES
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RESEARCHPROTOCOL
Dated8/15/2017
 
 
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



Anticipatedbenefits:
Theremaybenobenefittoindividualsubjects,buttheknowledgegainedfromthisstudyisexpectedto
provideimportantinsightstoguidefutureresearchoninitialandmaintenanceacupuncture
treatmentprotocolsforcontrolofvulvodyniapain.

Inclusioncriteria:
Potentialparticipantsmustfulfillthefollowing:

a) apreviousdiagnosisofgeneralizedvulvodyniaorprovokedvestibulodynia
b) 18to45yearsold
c) apainnowscore4orhigherwithtamponinsertionandremovalperformedattheinitial
screeningexam
d) speakandreadEnglish

Exclusioncriteria:
Potentialparticipantswillbeexcludedifanyofthefollowingistrue:

a) infectiousconditions
b) inflammatoryconditions
c) neoplasticdisorders
d) neurologicdisorders
e) traumatothegenitals
f) iatrogenic
g) hormonaldeficiencies
h) coͲmorbidpelvicpainconditions(toavoidconfoundingpainoutcomes)
i) 
pelvicinflammatorydisease
j) 
endometriosis
k) menopause
l) 
pregnancy
m) womenreceivingconcurrenttherapiesthatmaydecreasestressand/ormuscletension(i.e.,
concomitantphysicaltherapy,biofeedback,massage,orotheracupuncturesessions)willalsobe
excluded

Datacollectionandmanagement:
Someoftheresearchdatawillbecollectedelectronicallyusingalaptopcomputer.ThePAINReportIt
computerizedpainassessmentprogramdevelopedbyDr.Wilkietocollectsubjects’paininformation
willbecompletedonline.Subjects’datawillbewrittendirectlytotheCollegeofNursingserverandwill
notreside,eventemporarily,onthelaptopcomputer.HTTPSwillbeusedfordatatransfertotheCON
serverandthetransferfromthetablettotheserverisencrypted.Theapplicationwillbelocatedina
secureCollegeofNursingserverwithrestrictedaccess,withaccessonlytotheimmediatestudy

Title: DOUBLEͲBLINDPHASE2RCT:EFFECTOFACUPUNCTUREONPATIENTVULVODYNIAOUTCOMES
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personnel.Theotherquestionnaires(FemaleSexualFunctionIndex(FSFI),VulvarPainFunctional
Questionnaire,andtheDoubleͲBlindNeedleQuestionnaire)willbecompletedonpaper.

Allparticipantswillbeassignedacodenumberandtheirdatawillbeidentifiedonlywiththatcode
number.Thelinkofthecodenumberstothesubjectidentifierswillbekeptseparatefromthestudy
data.Onlytheinvestigatorsandkeypersonnelwillhaveaccesstothecode/masterkey.The
computerizeddatawillbestoredinacontrolledaccesscomputerdatabaseinasecureCollegeof
Nursingserver.AllharddatacollectedwillbestoredinalockedofficeintheCollegeofNursing.

DatamanagementprocedureswillbesupervisedbyDr.Steffen,thestatistician.

Dataanalysis:
Dr.Steffenwillsupervisealldataanalysisprocedures.Priortodatacollectionandentry,acodebookwill
becreatedwiththevariablenames,descriptions,andvaluecodesofeachvariable.Missingdatawillbe
minimizedthroughourretentioneffortsbutareinevitable,tosomedegree,inanylongitudinalstudy.
Wewilladdressmissingdatabyintentiontotreatanalyses(ITT),usingthefullinformationmaximum
likelihood(FIML)approach,whichhasbeenshowntoproduceunbiasedparameterestimatesand
standarderrors.Tobegintophenotypesubjectswithemotionaldisturbanceswewillexplorethe
emotionaldimensionofpainatbaselineandafterthe10thacupuncturetreatmentusingthewellͲknown
PainRatingIndexͲAffective(PRIͲA)scorefromPAINReportIt®.


Safetymonitoring:
Thestudyislowrisk.However,theresearchteamwillmonitorthesafetyofsubjectsduringstudy
procedures.Intheeventofinjuryrelatedtothisresearch,treatmentwillbeavailablethroughtheUIC
MedicalCenter.However,thepatientorthirdpartypayer,ifany,willberesponsibleforpaymentofthis
treatment.Patientsubjectswillremainunderthecareoftheirusualprovider,whowillbeavailableto
givethemusualcareifneeded.Anyunanticipatedproblemsrelatedtothestudyprocedurewillbe
immediatelyreportedtotheIRB.
