Transcranial Direct Current Stimulation for Freezing of Gait in Patients With Parkinson's Disease
Phase: NA
Conditions: Parkinson's Disease
Sponsor: University of Miami

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TI T L E:  
Tra nscra nial Direct C urre nt Sti m ulati o n f or Freezi n g of Gait i n 
Par ki ns o n’s Disease 
 
 
 
V E R SI O N N U M B E R:  
3  
 
 
 
V E R SI O N D A T E:    
9/ 2 / 2 0 1 6 
 
 
 
P R O T O C O L N U M B E R:  2 0 1 4 0 1 2 7 
 
 
 
I N V E S TI G A T O R N A M E: C or neli u C L uca 
 
 
 
N C T N U M B E R:    
  
N C T 0 2 2 6 6 0 0 4 
 
 
 
 

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1)  
Pr ot oc ol Title   
 
Tr a nscr a ni al Direct C urre nt Sti m ul ati o n f or Freezi n g of G ait i n P ar ki ns o n’s 
Dise ase  
 
2)  
I R B Re vie w Hist or y  
N/ A   
3)  
O bjecti ves  
T he g oal of t his researc h is t o q ua ntif y t he effects of u ni lateral a n o dal tra nscra nial 
direct c urre nt sti m ulati o n (t D C S) i n patie nts wit h Par ki ns o n’s D isease ( P D) a n d 
freezi n g of gait ( F O G).  We will test t he effects of u nilateral tra nscra nial direct 
c urre nt sti m ulati o n  (t D C S) i n c o m bi nati o n wit h l oc o m ot or trai ni n g.  
Ai m 1. Q u a ntif y t he effects of t D C S o n f reezi n g of g ait i n p atie nts wit h P D . t D C S will 
be a d mi nistere d t o get her wit h l oc o m ot or trai ni n g t o patie nts wit h P D a n d  wit h F O G. 
Te m p oral a n d s patial gait ki ne matics will be meas ure d usi n g a p orta ble acceler o meter -
base d s yste m. T he pri mar y o utc o me will be gait vel ocit y. Sec o n dar y o utc o mes will be  
Ti me d U p a n d G o Test  (si n gle a n d d ual-tas k), t he freezi n g of gait q uesti o n naire, U nifie d 
Par ki ns o n Disease Rati n g Scale  (U P D R S ), a n d perce nta ge ti me s pe nt wit h F O G d uri n g 
t he ti me d u p a n d g o ( T U G), a n d p ost ural s wa y w hile sta n di n g (si n gle a n d d ual-tas k). 
Ai m 2.  Q u a ntif y t he effects of a n o d al direct c urre nt sti m ul ati o n o n c ortic al 
e xcit a bilit y of t he m ot or c orte x.   Effects of a n o dal t D C S will be assesse d  i n patie nts 
wit h P D a n d  wit h freezi n g of gait. Tra nscra nial ma g netic sti m ulati o n ( T M S) will be use d 
t o pr o be c ortical e xcita bilit y a n d plasticit y of m ot or c orte x pre a n d p ost i nterv e nti o n. 
Ai m 3. E v al u ate t he c ortic al/s u bc ortic al c h a n ges i n d uce d b y t D C S.  We will use 
ma g netic res o na nce s pectr osc o p y ( M R S) t o i de ntif y c ha n ges i n brai n gl uta mate a n d 
G A B A i n patie nts wit h P D a n d F O G.  
 
4)  
B ac k gr o u n d 
T he ne ur ol o gical mec ha nis ms u n derl yi n g gait d ysf u ncti o n a n d i n partic ular freezi n g of 
gait ( F O G) are u n k n o w n, b ut it is t h o u g ht t hat i m paire d gait a ut o maticit y ma y ca use 
patie nts wit h Par ki ns o n’s D isease ( P D) t o rel y m ore hea vil y o n c ortical c o ntr ol f or 
l oc o m oti o n. It has bee n p ost ulate d t hat i nter ve nti o ns t hat rest ore t he n or mal e xcita bilit y 
of t he m ot or c orte x w o ul d be ass ociate d wit h better m ot or f u ncti o n 1( 1). N o ni n vasi ve 
tec h ni q ues s uc h as tra nscra nial direct c urre nt sti m ulati o n (t D C S) ha ve bee n e m pl o ye d i n 
vari o us ne ur ol o gical c o n diti o ns t o m o d ulate t he c ortical e xcita bilit y a n d wit h i m pr o ve d 
f u ncti o nal o utc o me. 
 

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St u dies of tra nscra nial direct sti m ulati o n  s u g gest t hat t D C S i m pr o ves f u ncti o n 
pres u ma bl y b y acti vati n g ce ntral ne ur o m o d ulat or y mec ha nis ms 2( 2) a n d s pi nal l oc o m ot or 
patter n ge nerati n g circ uitr y 3( 3). T he c urre nt pr o p osal see ks t o c o m bi ne t D C S a n d 
l oc o m ot or trai ni n g t o assess effects i n wal ki n g i n patie nts wit h P D.  t D C S decreases t he 
t hres h ol d f or ne ur o nal e xcita bilit y a n d has ne ur o m o d ulat or y effects o n c ortical a n d 
s u bc ortical str uct ures i m pr o ves t he m ot or a n d c o g niti ve f u ncti o ns i n P D 4( 4). We 
h y p ot hesize t hat t D C S i n c o m bi nati o n wit h l oc o m ot or trai ni n g will re d uce freezi n g of 
gait. T he effects o n c ortical e xcita bilit y will be q ua ntifie d usi n g T M S a n d 
ne ur otra ns mitter c ha n ges ass ociate d wit h t his i nter ve nti o n will be e x pl ore d usi n g M R 
s pectr osc o p y.  
 
T he l o n g- ter m g oal of t his pr oject is t o de vel o p strate gies f or pers o ns wit h P D t hat will 
facilitate o pti mal rest orati o n of wal ki n g f u ncti o n. T hese st u dies are si g nifica nt i n t hat 
t he y will a d va nce t he fiel d as relates t o: 1) de vel o p me nt of o pti mal strate gies t o i m pr o ve 
wal ki n g f u ncti o n i n patie nts wit h P D, a n d 2) u n dersta n di n g t he d ysf u ncti o n ne ural 
net w or ks i n v ol ve d i n F O G.  T he st u dies are i n n o vati ve i n t hat t he y: 1) deter mi ne t he 
val ue of usi n g t D C S as a c o n diti o ni n g i nter ve nti o n t o m o d ulat e t he e xcita bilit y of t h e 
ner v o us s yste m a n d t here b y i m pr o ve res p o nsi ve ness t o trai ni n g, 2) see k n o n-
p har mac ol o gical a p pr oac hes f or ma na gi n g F O G a n d 3) e x pl ore t he mec ha nis m of acti o n 
of t D C S o n F O G. 
  
I de ntif yi n g n o ni n vasi ve t hera pies f or wal ki n g w o ul d bri n g a si g nifica nt be nefit f or 
patie nts wit h P D, i ncrease q ualit y of life a n d decrease b ur de n o n care gi vers. T his 
researc h is rele va nt f or t he a gi n g p o p ulati o n i n t he U nite d States a n d ma y be be neficial 
f or patie nts wit h ot her ne ur ol o gical c o n diti o ns s uc h as fr o ntal gait dis or ders, patie nts wit h 
w hite matter disease a n d c o g niti ve i m pair me nt . I de ntif yi n g t he best sti m ulati o n 
para meters wit h t he least si de effects will set t he sta ge f or f ut ure cli nical trials.  
 
5)  
Incl usi o n a n d E xcl usi o n Criteri a  
Patie nts wit h Pa r ki ns o n’s Disease as deter mi ne d b y t he U K Brai n Ba n k Criteria 
a n d H oe h n a n d Ya hr ( H & Y ) sta ges 2- 3 will be c o nsi dere d f or e nr oll me nt. Patie nts 
will be scree ne d at t he U ni versit y  of Mia mi M o ve me nt Dis or der s Cli nic b y t he 
Pri nci pal I n vesti gat or ( PI ) a n d his tea m .  
 
I ncl usi o n Criteria:  
•  A ge s 1 8- 8 0 
•  Par ki ns o n’s D isease H oe h n a n d Ya hr sta ges 2- 3 
•  Prese nce of Freezi n g of Gait as per t he freezi n g of gait q uesti o n naire. 
Partici pa nts will q ualif y if t he y re p ort 2 or m ore e pis o des of freezi n g per 
wee k  

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•  S ta ble me dicati o n re gi me n 
•  Ti me t o c o m plete Ti me d u p a n d g o ( T U G) bet wee n greater t ha n 1 2 sec o n ds 
 
E xcl usi o n criteria : 
•  M e dical or ort h o pe dic c o n diti o n s t hat w o ul d i nterfere wit h gait trai ni n g f or 
3 0 mi n utes 
•  U na ble t o perf or m ti me d u p a n d g o   
•  Hist or y of seiz ures 
•  Im pla nte d dee p brai n sti m ulat or , pace ma ker or a n y ot her electr o nic de vice 
•  D e me ntia  as defi ne d b y mi ni -me ntal state e xa mi nati o n ( M M S E) e q ual t o 
or bel o w 2 4 
•  A d ults u na ble t o c o nse nt, i n di vi d uals w h o are n ot yet a d ults (i nfa nts, 
c hil dre n, tee na gers) p re g na nt w o me n  a n d pris o ners will n ot be c o nsi dere d 
f or partici pati o n 
 
6)  
N u m ber of S u bjects  
 
F ort y s u bjects wit h P D a n d F O G will be recr uite d.  S u bjects wit h dia g n osis of P D 
acc or di n g wit h U K P D brai n ba n k criteria, H & Y sta ge 2- 3 a n d prese nce of F O G will be 
c o nsi dere d f or t he st u d y.   
 
7)  
St u d y -Wi de Recr uit me nt Met h o ds  
 
P ote ntial s u bjects will be recr uite d fr o m t he cli nics at t he U ni versit y of Mia mi - 
M o ve me nt Dis or der s Researc h Ce nter , ot her healt h care pr o vi ders i n t he Mia mi 
c o m m u nit y a n d t he l ocal Mia mi c o m m u nit y t hr o u g h s u p p ort gr o u ps a n d p u blic s paces. 
A n e x perie nce d cli nical trial tea m is c urre ntl y i n place t o ass ure t hat t he st u dies are 
c o n d ucte d i n a ma n ner w hic h all o ws f or acc urate, efficie nt a n d ti mel y c ollecti o n of data 
a n d pro vi des a safe a n d pleasa nt e n vir o n me nt f or t he patie nts. T he Cli nical Trial Staff 
ha ve all recei ve d trai ni n g a n d certificati o n t o c o n d uct cli nical trials fr o m t he U ni versit y 
of Mia mi Researc h A d mi nistrati o n a n d ha ve bee n trai ne d a n d c urre ntl y f oll o w G o o d 
C li nical Practice G ui deli nes t o ass ure t he safet y a n d pr otecti o n of st u d y partici pa nts. T he 
Ce nter c urre ntl y w or ks cl osel y wit h t he Nati o nal Par ki ns o n F o u n dati o n a n d all of its l ocal 
c ha pters a n d s u p p ort gr o u ps t o facilitate patie nt recr uit me nt t hr o u g h m ult i ple res o urces 
pr o vi de d t o t he Ce nter b y t he Nati o nal Par ki ns o n F o u n dati o n.  
 
T he st u d y i n vesti gat ors will disc uss t he st u d y wit h patie nts w h o ha ve bee n dia g n ose d 
wit h Par ki ns o n’s D isease a n d meet t he eli gi bilit y criteria. Patie nts wit h Par ki ns o n’s 

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Disease  H & Y  sta ge 2- 3, o n a sta ble me dicati o n re gi me n a n d wit h o ut maj or me dical 
pr o ble ms ( i.e., car diac pr o ble ms, mali g na nc y, h/ o of seiz ures) will be ca n di dates f or t he 
st u d y. T he s u bjects will be pr o vi de d wit h a n o ver vie w of t he o bjecti ves a n d pr oce d ures, 
a n d wit h a n i nf or me d c o nse nt f or m i n t heir la n g ua ge. If patie nts a gree t o partici pate i n t he 
st u d y a scree ni n g visit will be sc he d ule d t o assess t he eli gi bilit y f or partici pati o n. 
 
8)  
St u d y Ti meli nes  
Eac h  i n di vi d ual selecte d t o partici pate will partici pate i n i n a baseli ne e val uati o n 
visit , 9 trai ni n g visits, a n d p ost-test e val uati o n visit. E val uati o n visits are 
esti mate d t o be 3 h o urs, a n d trai ni n g visits 4 5 mi n utes.  
Visit # 1 - Pre -test assess me nt i ncl u di n g gait, p ost ural s wa y, c o g niti o n a n d T M S 
meas ures will be c ollecte d. Partici pa nts ma y di vi de t his i nt o t w o sessi o ns, t o 
acc o m m o date f or a s h orter test d urati o n. 
Visit # 2 - 9- Partici pa nts will partici pate i n a 3 0 mi n ute gait trai ni n g pr ot oc ol 
a d mi nistere d b y trai ne d pers o n nel wit h t D C S a u g me ntati o n. T hese visits will be 
sc he d ule d 3 ti mes per wee k f or 3 wee ks t otali n g 9 trai ni n g sessi o ns.  
Visit # 1 0 - P ost -test gait, p ost ural s wa y, c o g niti o n a n d T M S meas ures will be 
c ollecte d. Partici pa nts ma y di vi de t his i nt o t w o sessi o ns t o acc o m m o da te f or a 
s h orter test d urati o n.  
We esti mate  t he st u dy will be c o m plete d i n o ne year . 
9)  
St u d y E n d p oi nts  
 
•  Pri mar y o utc o me c ha n ge i n wal ki n g s pee d  
•  Sec o n dar y o utc o mes are:  
•  Freezi n g of gait:  freezi n g of gait q uesti o n naire, ti me s pe nt wit h freezi n g of 
gait  
•  M ot or f u ncti o n: m ot or sc ores of Par ki ns o n’s Disease- U P D R S ( part 3) 
•  L oc o m ot or f u ncti o n ( bi o mec ha nical a nal ysis [ Gait M o bilit y La b s yste m]): 1 0 
meter wal k  (s pee d a n d stri de le n gt h), T U G (si n gle a n d d ual-tas k), p ost ural 
c o ntr ol ( p ost ural s wa y) 
•  Ne ur o p h ysi ol o gical:  m ot or t hres h ol d of t he primar y m ot or area as meas ure d 
b y T M S , a n d Gl uta mate/ G A B A rati o , as meas ure d b y M R S. 
•  Ne ur o ps yc h ol o gical : bac k war d di git s pa n, oral versi o n of t he trail ma ki n g test, 
M o ntreal c o g niti ve assess me nt ( M O C A), a n d t he c o ns o na nt tri gra ms test  
 
1 0)  Pr oce d ures I n v ol ve d  
 
A feasi bilit y st u d y will be perf or me d t o e val uate t he i nfl ue nce  of t D C S i n c o nj u ncti o n 
wit h l oc o m ot or trai ni n g ( L T) i n partici pa nts  wit h P D. Partici pa nts will u n der g o a batter y 

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baseli ne assess me nts, f oll o we d b y 3 wee ks of l oc o m ot or trai ni n g ass ociate d wit h t D C S. 
After trai ni n g, partici pa nts will u n der g o a batter y of p ost- test assess me nts. 
 
O n t he first visit ( baseli ne assess me nts), all o utc o mes o utli ne d i n secti o n 9 ( St u d y 
E n d p oi nts) will be perf or me d . Baseli ne a n d p ost -test assess me nts will be perf or me d b y 
t he st u d y pers o n nel a n d u n der t he s u per visi o n of t he pri nci pal i n vesti gat or a n d c o-
i n vesti gat or at t he De part me nt of Ne ur ol o g y, U ni versit y of Mia mi Miller Sc h o ol of 
Me dici ne.  
 
L oc o m ot or trai ni n g ( L T) will ta ke place f oll o wi n g t he pre -test assess me nt. Part ici pa nts 
will e n ga ge i n l oc o m ot or trai ni n g 3 ti mes per wee k, i n 3 0 mi n ute sessi o ns, f or a t otal of 9 
sessi o ns. D uri n g L T , partici pa nts will recei ve n o n- i n vasi ve t D C S ( 2 m A, P h ores or de vice) 
a p plie d t o t he s u p ple me ntar y m ot or area of t he he mis p here c o ntr olli n g t he wea ker le g, 
utilizi n g s u perficial s mall electr o des a p plie d t o t he partici pa nt’s scal p. Sti m ulati o n will be 
a d mi nistere d u n der t he s u per visi o n of t he c o-i n vesti gat or, w h o m has e x pertise i n brai n 
sti m ulati o n a n d has a trac k-rec or d t hat i ncl u des t he use of t D C S i n ne ur ol o gical 
p o p ulati o ns. L T  will be a d mi nistere d b y a lice nse d p h ysical t hera pist  at t he U ni versit y of 
Mia mi We ll ness Ce nter ( me dical ca m p us a n d/ or c oral ga bles ca m p us).  
 
F oll o wi n g t he 3 -wee k trai ni n g, partici pa nts  will u n der g o p ost-testi n g, w herei n t he y will 
re peat all o utc o mes o utli ne d i n secti o n 9 ( St u d y E n d p oi nts).  
 
 
Data A nal ysis : 
O utc o me meas ures ( pri mar y a n d sec o n dar y) p ost-trai ni n g will be c o m pare d t o pre-
trai ni n g val ues. T he data will be  i ns pecte d f or h o m o ge neit y of varia nce a n d n or malit y of 
distri b uti o n. We will test f or si g nifica nt c ha n ges  i n o utc o mes of m ot or f u ncti o n, 
l oc o m ot or f u ncti o n, ne ur o ps yc h ol o gical perf or ma nce a n d ne ur o p h ysi ol o gical o utc o me 
meas ures fr o m pre- test t o p ost-test. Statistical a nal ys is will be perf or me d usi n g t he 
Statistical pac ka ge f or t he S ocial Scie nces 1 5. 0 ( S P S S,  C hica g o, Illi n ois). A paire d t- test 
will be use d t o c o m pare t he effects fr o m pre-i nter ve nti o n t o p ost-i nter ve nti o n. T he 
si g nifica nce le vel f or t he st u d y will be set at al p ha < 0. 0 5.  
 
Testi n g Pr oce d ures  
Assess me nts will be perf or me d w hile partici pa nts are O N me dicati o n.  
G ait s pee d a n d stri de le n gt h - T hese o utc o mes will be meas ure d d uri n g t he 1 0 meter 
wal k a n d T U G usi n g t he Gait M o bilit y La b S yste m ( A P D M de vice). T he best 3 
rec or di n gs o ut of 5 meas ure me nts will be use d f or q ua ntificati o n.  
T U G - W ill be meas ured usi n g a st o p watc h, a n d t he Gait M o bilit y La b S yste m ( A P D M 
de vice) . F or healt h y s u bjects t he mea n val ue of T U G is 9. 5 2 sec wit h S D of 1. 3 8 w hile 
f or Par ki ns o n’s patie nts t he mea n val ue of T U G is 1 3. 8 3 sec S D 4. 4 1. T he best 3 
rec or di n gs o ut of 5 meas ure me nts will be use d f or q ua ntificati o n. P ost ur al c o ntr ol : 
p ost ural s wa y will be q ua ntifie d d uri n g q uiet sta n di n g, a n d q uiet sta n di n g w hile 

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perf or mi n g a serial s u btracti o n tas k usi n g t he Gait M o bilit y La b S yste m ( A P D M de vice).  
T he best 3 rec or di n gs o ut of 5 meas ure me nts will be use d f or q ua ntificati o n.  
 
F O G Q - Freezi n g of gait Q uesti o n naire ( F O G Q) will be a d mi nistere d b y a trai ne d 
me m ber of t he st u d y tea m. . It c o nsists of 1 6 ite ms re gar di n g gait a n d falls a n d is re p orte d 
as a sc ore fr o m 0- 1 6.  
 
U P D R S - U nite d Par ki ns o n’ s D isease R ati n g Scale ( U P D R S) will be perf or me d  b y a 
trai ne d me m ber of t he st u d y tea m.  T he U P D R S c o ntai ns 4 secti o ns. Part 1 assesses t he 
n o n- m ot or as pects of dail y li vi n g, part 2 assesses m ot or as pects of dail y li vi n g, part 3 is a 
m ot or e xa mi nati o n of P D a n d part 4 q ua ntifies t he prese nce of m ot or c o m plicati o ns li ke 
d ys ki nesias, fl uct uati o ns or  d yst o nia. 
 
 
 
Ne ur o p h ysi ol o gic al assess me nt - We will use si n gle p ulse T M S t o e val uate t he 
e xcita bilit y of t he pri mar y m ot or area utilizi n g t he Ma g pr o X 1 0 0 de vice a n d a fi g ure- of-
ei g ht c oil . S urface electr o des will be place d o n t he first d orsal i nter osse o us ( F DI), a n d 
m ot or e v o ke d p ote ntials will be elicite d t o deter mi ne t hres h ol d of acti vati o n a n d 
a m plit u de of res p o nse at sti m ulat or i nte nsit y of 1 2 0 % of m ot or t hres h ol d.   
 
M R s pectr osc o p y will be perf or me d wit h a 3 T ma g net. Si n gle -v o xel ac q uisiti o n met h o d 
w ill be use d t o ac q uire data fr o m t he pri mar y m ot or c orte x t o meas ure gl uta mate a n d 
gl uta mi ne. A n i n - h o use de vel o pe d s oft ware b y Dr . Ma u dsle y 
5( 1 9) will be use d t o 
q ua ntif y meta b olites fr o m s uc h T E -a vera ge d s pectra wit h  si m ulate d s pectral pri or 
ge nerate d usi n g t he N M R para meters of t he meta b olites of i nterest - fi g ure 1 6( 2 0). G A B A 
i n t he me dial pri mar y m ot or c orte x re gi o n will be meas ure d usi n g a p u blis he d e dite d 
si n gle- v o xel M R s pectr osc o pic met h o d 7( 2 1). 
 
I nter ve nti o n a n d Tr ai ni n g Pr oce d ures 
t D C S i nter ve nti o n: a n o dal t D C S of t he s u p ple me ntar y m ot or area of t he he mis p here 
c o ntr olli n g t he wea ker le g ( deter mi ne d b y ver bal re p ort) will be deli ve re d d uri n g e ver y 
trai ni n g sessi o n (t otal ti me = 3 0 mi ns, i nte nsit y =2 m A)  w hile  partici pa nts are  i n t he O N 
state of t heir me dicati o n sc he d ule. 
L oc o m ot or Trai ni n g: T he trai ni n g para di g m will f oc us o n strate gies f or w hic h t here is 
e vi de nce of effecti ve ness i n pe rs o ns wit h P D. Briefl y, d uri n g t he first wee k, i n di vi d uals 
practice t he pri mar y m ot or tas k, a n d m ot or d ual tas ks ( D Ts), recei ve fre q ue nt fee d bac k a n d 
ma ke us e of a u dit or y a n d vis ual c ues. O n t he sec o n d wee k, c o g niti ve -m ot or D Ts are 
i ntr o d uce d a n d vis ual a nd a u dit or y c ues are decrease d or re m o ve d i n a n eff ort t o i ncrease t he 
c halle n ge a n d t o ai d t he i n di vi d ual i n esta blis hi n g a n i nter nal re pres e ntati o n of t he 
re q uire me nts necessar y t o carr y o ut t he wal ki n g trai ni n g. Tas ks i ncrease i n c o m ple xit y i n 
wee ks 2 a n d 3 t o pr o m ote tra nsfere nce of p ossi ble gai ns i n gait perf or ma nce t o ot her m ot or 
be ha vi ors f o u n d dail y life wit h o ut de pe n de nce o n e xter nal sti m uli.  

I R B St u d y N u m ber: 2 0 1 4 0 1 2 7 
Versi o n 3, Date: 9/ 2/ 2 0 1 6 
 
 
 
 
Pa ge 8 of 1 4  
R e vis e d : M a y 2 6, 2 0 2 0  
 
 
1 1)  D at a a n d S peci me n B a n ki n g 
N/ A  
1 2)  D at a M a n a ge me nt 
 
We esti mate d t he p o wer base d o n a ra n ge of sa m ple sizes, effect sizes  at a 0. 0 5 
si g nifica nce le vel wit h a t w o-si de d t test. A t otal sa m ple size of at least 4 0 P D patie nts 
will ac hie ve at least 8 0 % p o wer t o u nc o ver a n effect size of 0. 9 4 at a si g nifica nce le vel of 
0. 0 5 f or a t w o- si de d test. T his effect size is c orres p o n di n g t o a mea n differe nce of 1 5 % 
( 1 5. 2c m/s) gi ve n t hat t he s q uare r o ot of t he wit hi n mea n s q uare err or is 1 6. We 
perf or me d t he p o wer a nal ysis usi n g P A S S 2 0 0 8 S oft ware ( N C S S, Ka ys ville, U T). F or t he 
data a nal ysis, we will esti mate t he effect of t D C S o n c ha n ges i n gait vel ocit y, T U G a n d 
U P D R S sc ore usi n g mi x- effects m o dels. All a nal yses will be c o n d ucte d usi n g S A S 
( versi o n 9. 2, S A S I nstit ute I nc., Car y, N C). 
 
All data files will be sec ure d at t he  U ni versit y of Mia mi. Data  ma na ge me nt will be 
m o nit ore d b y t he PI o n a n o n- g oi n g basis.  
 
Pa per rec or ds: 
Pa per rec or ds will be h o use d i n a l oc ke d file ca bi net, i n a l oc ke d r o o m, wit h c o ntr olle d 
access. O nl y t he PI a n d ass ociate d researc h staff will ha ve access  t o t he rec or ds. Eac h 
partici pa nt will be assi g ne d a u ni q ue st u d y I D n u m ber. T his I D is affi xe d t o all data 
f or ms a n d is ke pt se parate fr o m t he i n di vi d ual's i de ntif yi n g i nf or mati o n, e xce pt i n o ne 
electr o nic  file w hic h is pass w or d-pr otecte d a n d accessi ble o nl y b y t he PI.  
St u d y partici pa nts will n ot be s pecifi call y i de ntifie d i n a n y p u blicati o n of t he researc h 
res ults.  
 
Rec or ds will be ke pt f or 7 years after c o m pleti o n  of t he st u d y, at w hic h ti me t he y ma y be 
destr o ye d. 
 
1 3)  Pr o visi o ns t o M o nit or t he D at a t o E ns u re t he S afet y of S u bjects 
 
Data M o nit ori n g:  
Data a n d safet y m o nit ori n g will be t he pri mar y res p o nsi bilit y of t he C o-I n vesti gat or, wit h 
o n- g oi n g  o versi g ht b y t he st u d y PI. All partici pa nt pers o nal a n d me dical i nf or mati o n will 
be treate d as c o nfi de ntial a n d safe g uar de d i n acc or da nce wit h t he Pri vac y A ct of 1 9 7 4 
a n d t he Healt h I ns ura nce P orta bilit y a n d Acc o u nta bilit y Act of 1 9 9 6 ( HI P A A) w hic h 
pr ote c ts t he pri vac y of i n di vi d uall y i de ntifia ble healt h i nf or mati o n, a n d i de ntifia ble 
i nf or mati o n bei n g use d t o a nal yze patie nt safet y e ve nts a n d i m pr o ve patie nt safet y. 
 
Safet y:  
Safet y of partici pa nts will be m o nit ore d b y t he C o-I n vesti gat or o n a n o n- g oi n g basis a n d 
re vie we d b y t he st u d y PI o n a wee kl y basis. T he st u d y PI will be i nf or me d i m me diatel y 
of a n y s us pecte d a d verse effects.  

I R B St u d y N u m ber: 2 0 1 4 0 1 2 7 
Versi o n 3, Date: 9/ 2/ 2 0 1 6 
 
 
 
 
Pa ge 9 of 1 4  
R e vis e d : M a y 2 6, 2 0 2 0  
 
 
 
All testi n g a n d trai ni n g pr oc e d ures will be perf or me d b y q ualifie d pers o n nel at t he 
U ni versit y of Mia mi Well ness Ce nter  ( miller sc h o ol of me dici ne a n d/ or c oral ga bles), 
w hic h is l ocate d mi n utes fr o m a n e mer ge nc y r o o m.  
 
I n t he e ve nt of a n o n-seri o us a d verse reacti o n d uri n g partici patio n i n t he st u d y, a staff 
me dical  p h ysicia n will be i m me diatel y pa ge d or t he partici pa nt will be esc orte d t o t he 
e mer ge nc y r o o m. I n t he e ve nt of a n e mer ge nc y, t he E M S will be acti vate d; first 
res p o n ders will i m me diatel y i nitiate basic e mer ge nc y pr oce d ures a n d c o nti n ue u ntil E M S 
arri ves.  
 
A d verse effects re p orti n g:  
T he pri nci ple i n vesti gat or will c o m pl y wit h t he re q uire d a n n ual re p orti n g of  n o n-seri o us 
a n d seri o us a d verse e ve nts t o t he I R B, Ge neral Cli nical Researc h Ce nter ( G C R C), a n d 
Researc h S u bject A d v ocac y ( R S A) pr o gra m of t he U ni versit y of Mia mi. 
 
1 4)  Wit h dr a w al of S u bjects 
 
T he f oll o wi n g cli nical criteria will be use d f or wit h dra wi n g a partici pa nt fr o m t he st u d y:  
T h e pri nci p al i n vesti gat or will wit h dra w p arti ci p a nts w h o b ec o me i neli gi bl e t o p artici p at e i n t he 
st u d y ( as p er st u d y i ncl usi o n a n d e x cl usi o n criteri a), or if t here is a s af et y c o n cer n f or t he 
p artici p a nt or st u d y i n vesti gat ors i ncl u di n g s ei z ur e, p ai n or i nt olera ble si d e eff ects.  
. 
1 5)  Ris ks t o S u bjects  
 
1) T he re is a ris k of seiz ure ass ociate d wit h t he use of tra nscra nial ma g netic sti m ulati o n 
( T M S), b ut t his is c o nsi dere d re m ote (less t ha n 1 i n 1 0, 0 0 0) pr o vi de d t hat t here is n o 
hist or y of: a ) e pile ps y; b) seiz ure; c) hea d i nj ur y; or d) str o ke.  
T here is a ris k of m o ve me nt of i m pla nte d bi o me dical de vices, t heref ore,  s u bjects w o ul d 
n ot be a p pr o priate f or t his st u d y if t he y ha ve: metal plates, bl o o d vessel cli p  or a n y 
i m pla nte d bi o me dical de vice i n y o ur hea d. T here is n o ris k i n v ol ve d re gar di n g i m pla nte d 
plates  or scre ws i n t he cer vical s pi ne. S u bjects will be scree ne d f or hist or y pri or t o 
i ncl usi o n. 
 
2) Tra nscra nial ma g netic sti m ulati o n ( T M S) – S u bjects will feel a l ocal t witc h of t he 
scal p a n d nec k a n d i n v ol u ntar y m o ve me nt of t heir left le g, pr o vi de d t here are s ufficie nt 
n u m bers of i nta ct desce n di n g fi bers t o c o n d uct t he electrical si g nal. I nf or mati o n of 
i nterest i ncl u des t he ma g nit u de of t he c o ntracti o n. T he F D A c o nsi ders t he si n gle- p ulse 
T M S s yste m a “ n o n -si g nifica nt ris k” de vice. Alt h o u g h t he ris k f or seiz ure is l o w wit h 
si n gle p ulse T M S, all st u d y pers o n nel are trai ne d i n h o w t o res p o n d a p pr o priatel y t o a 
seiz ure, b y kee pi n g t he s u bject safe d uri n g t he e ve nt a n d acti vati n g e mer ge nc y me dical 
res p o nse. As all T M S pr oce d ures will be perf or me d at t he Ce nter of Ne ur ol o g y, t he st u d y 
PI a n d me dical pers o n nel will be prese nt i n t he b uil di n g t o assist wit h a d diti o nal nee ds. 

I R B St u d y N u m ber: 2 0 1 4 0 1 2 7 
Versi o n 3, Date: 9/ 2/ 2 0 1 6 
 
 
 
 
Pa ge 1 0 of 1 4  
R e vis e d : M a y 2 6, 2 0 2 0  
 
 
All s u bjects will be scree ne d d uri n g t he i nitial e val uati o n t o e ns ure t hat t he y d o n ot ha ve 
i m pla nte d metal de vices i n t he hea d, t o decrease t he ris k of a n y p ote ntial a d verse e ve nts . 
A mil d a n d tra nsie nt hea dac he ca n occ ur (a p pr o xi matel y 1 i n 4 s u bjects) a n d t here ha ve 
bee n n o a d verse reacti o ns i n a n y of t he m ore t ha n 1 0 0 s u bjects we ha ve st u die d usi n g 
T M S t o date. It s h o ul d be e m p hasize d t hat T M S is n o w i n wi des prea d use ar o u n d t he 
w orl d, b ot h f or electr o p h ysi ol o gical testi n g a n d m ore rece ntl y f or certai n f or ms of 
t hera p y. 
 
3 ) T he sti m ulati o n pr ot oc ols relati n g t o t he st u d y are si milar t o t h ose use d i n pre vi o us 
st u dies. S u bject ma y e x perie nce mi n or irritati o n fr o m t he t D C S el ectr o des o ver t he 
sti m ulati o n sites. Mil d re d ness o ver sti m ulati o n sites occ urs i n s o me s u bjects a n d 
ge nerall y s u bsi des wit hi n 1 5 mi n utes. T his will be  m o nit ore d cl osel y f oll o wi n g re m o val 
of t he sti m ulat or i n i nitial trials. S u bjects ma y als o be a d vise d  t hat t he y ma y feel a 
ti n gli n g c urre nt i n t he ge neral area of sti m ulati o n.  S u bjects ma y als o feel te m p orar y 
m uscle s ore ness f oll o wi n g partici pati o n d ue t o i ncrease d m uscle  s ore ness d ue t o 
i ncrease d l o wer li m b acti vit y de ma n ds a n d i nte nsit y of acti vit y. T here are n o d oc u me nte d 
st u dies re p orti n g a d verse si de effects of t D C S.  
 
4) Pe o ple are at ris k f or i nj ur y fr o m t he M RI ma g net if t he y ha ve pace ma kers or ot her 
i m pla nte d electrical de vices, brai n sti m ulat ors, de ntal i m pla nts, a ne ur ys m cli ps ( metal 
cli ps o n t he wall of a lar ge arter y), metallic pr ost heses (i ncl u di n g metal pi ns a n d r o ds, 
heart val ves, a n d c oc hlear i m pla nts), per ma ne nt e yeli ner, i m pla nte d deli ver y p u m p, or 
s hra p nel fra g me nts. Wel ders a n d metal w or kers are als o at ris k f or i nj ur y beca use of 
p ossi ble s mall metal fra g me nts i n t he e ye of w hic h t he y ma y be u na ware. We will scree n 
f or t hese c o n diti o ns pri or t o t he st u d y wit h a n M RI Safet y Q uesti o n naire, a n d if t he 
patie nt has a n y ris k fact ors, will n ot recei ve a n M RI sca n. If t here is a q uesti o n a b o ut t he  
prese nce of metal o bjects i n y o ur b o d y, s u bjects will be e xcl u de d fr o m partici pati o n. I n 
a d diti o n, we will as k s u bjects t o re m o ve all ma g netic o bjects (e. g. watc hes, c oi ns, 
je welr y, cre dit car ds) bef ore e nteri n g t he M RI sca n r o o m. Ot her wise, t here are n o k n o w n 
l o n g-ter m ris ks or c o nse q ue nces of M RI s ca ns. 
 
1 4) P ote nti al Be nefits t o S u bjects  
It is u n k n o w n w het her s u bjects will be nefit fr o m t his researc h st u d y alt h o u g h pre vi o us 
st u dies ha ve de m o nstrate d t hat fu ncti o nal gait trai ni n g has bee n s h o w n t o i m pr o ve gait 
para meters  i n i n di vi d uals wit h l oc o m oti o n d ysf u ncti o n d ue t o Par ki ns o n’s Disease. 
 

I R B St u d y N u m ber: 2 0 1 4 0 1 2 7 
Versi o n 3, Date: 9/ 2/ 2 0 1 6 
 
 
 
 
Pa ge 1 1 of 1 4  
R e vis e d : M a y 2 6, 2 0 2 0  
 
 
1 6)  V ul ner a ble P o p ul ati o ns  
 
N/ A  
 
1 7)  M ulti -Site Rese arc h  
 
N/ A  
 
1 8)  C o m m u nit y- B ase d P artici p at or y Rese arc h  
 
N/ A  
 
1 9)  S h ari n g of Res ults wit h S u bjects  
T he st u d y res ults will be s hare d wit h t he scie ntific c o m m u nit y a n d will be 
p u blis he d. 
2 0)  Setti n g  
Patie nts will be scree ne d at t he U M M o ve me nt Dis or ders Cli nic. T he 
researc h will be perf or me d at t he U ni versit y of Mia mi Well ness Ce nter  
( miller sc h o ol of me dici ne a n d/ or c oral ga bles ca m p us). M RIs will  be 
perf or me d at U M A p ple ba u m Ce nter b y Dr . G o vi n d Vara n. 
2 1)  Res o urces A v ail a ble 
Dr. J o yce G o mes -Os ma n. P h D, P T is a researc h ne ur oscie ntist wit h 
e xte nsi ve e x perie nce i n cli nical researc h a n d n o n- i n vasi ve brai n 
sti m ulati o n a p pr oac hes, w hic h i ncl u de tra nscra nial ma g netic sti m ulati o n 
( T M S) a n d electr oe nce p hal o gra p h y ( E E G). Dr. G o mes-Os ma n  has a 
p u blicati o n rec or d t hat i ncl u de st u dies utilizi n g n o n -i n vasi ve brai n 
sti m ulati o n t o c haracterize t he ne ur o p h ysi ol o g y a n d i n d uce 
ne ur osti m ulati o n (as a p ote ntial t hera pe utic a p pr oac h) i n i n di vi d uals wit h 
ne ur ol o gic i m pair me nts fr o m s pi nal c or d i nj ur y. Her e x perie nce i n cli nical 
trials are a res ult of 6 years w or ki n g at t he Mia mi Pr oject t o C ure 
Paral ysis, U ni versit y of Mia mi, w here s he was a pr oject c o or di nat or f or 
t w o R 0 1 gra nts, w hile w or ki n g o n her d oct oral st u dies. Dr. G o mes-Os ma n  
has e x pa n de d her k n o wle d ge i n Ne ur ol o g y a n d n o n- i n vasi ve brai n 
sti m ulati o n tec h ni q ues d uri n g her p ost d oct oral fell o ws hi p wit h Dr. Al var o 
Pasc ual -Le o ne, a n i nter nati o nall y rec o g ni ze d lea der i n t his fiel d, at t he 
Bere ns o n- Alle n Ce nter f or N o n- I n vasi ve Sti m ulati o n at Bet h Israel 
Deac o ness Me dical Ce nter at Har var d Me dical Sc h o ol. S he re mai ns 
affiliate d as a researc h sc h olar, a n d is c urre ntl y c o n d ucti n g st u dies t o 
i n vesti gate t he effects of aer o bic e xercise o n ne ur o plasticit y a n d c o g niti ve 
f u ncti o n i n healt h y i n di vi d uals. I n a d diti o n, s he is a lect urer at t he 
“I nte nsi ve C o urse i n Tra nscra nial Ma g netic Sti m ulati o n”, or ga nize d b y 
t his Ce nter.  

I R B St u d y N u m ber: 2 0 1 4 0 1 2 7 
Versi o n 3, Date: 9/ 2/ 2 0 1 6 
 
 
 
 
Pa ge 1 2 of 1 4  
R e vis e d : M a y 2 6, 2 0 2 0  
 
 
Dr . C or neli u L uca has e x perie nce wit h pers o ns wit h Par ki ns o n’ s D isease 
a n d sees patie nts i n t he M o ve me nt Dis or ders Cli nic at U M w here ma n y 
patie nts wit h freezi n g of gait are referre d. He is c urre ntl y f u n de d b y t he 
A merica n Aca de m y of Ne ur ol o g y a n d will s pe n d 2 5 % of his ti me f or t his 
pr oject.  
Dr. J or d y n Rice, P T, D P T is t he l ea d p h ysical t hera pist i n t his st u d y. S he is a 
res ear c h assist a nt i n t h e Ne ur o m ot or a n d Plasticit y la b c urre ntl y w or ki n g t o 
c o m plete her P h D st u dies i n P h ysi cal T h era p y u n d er t he  n e ur o m ot or trac k. S he 
has a cli nic al b ac k gr o u n d w or ki n g i n a v ari et y of setti n gs i ncl u di n g o ut p ati e nt 
ort h o p e dics a n d ne ur ol o g y, ac ute c are i n t h e tr a u ma I C U at a l e v el 1 tra u m a 
ce nter, a n d i n p ati e nt ne ur ol o gic al a n d p ost tra u ma re ha bilitati o n at t he S he ph er d 
Ce nter i n Atl a nt a, G A.  
2 2)  Pri or A p pr o v als  
N/ A  
2 3)  Recr uit me nt Met h o ds  
Partici pa nts will be recr uite d fr o m t he M o ve me nt Dis or der s Cli nic at U M.   
2 4)  C o m pe ns ati o n 
Partici pa nts w h o c o m plete all visits will recei ve a n i nce nti ve of $ 8 5 t otal 
w hic h will als o ai de i n o ffsetti n g t he c ost of par ki n g a n d tra ns p ortati o n. 
 
2 5)  L oc al N u m ber of S u bjects  
We will st u d y a t otal of 4 0 partici pa nts  t o ac hie ve a de q uate p o wer a n d 
acc o u nt f or p ote ntial varia bilit y wit hi n o ur sa m ple . 
2 6)  C o nfi de nti alit y 
 
T he site I n vesti gat or will ass ure t hat t he pri vac y of s u bjects, i ncl u di n g t heir 
pers o nal i de ntit y a n d pers o nal me dical i nf or mati o n, will be mai ntai ne d at all ti mes 
acc or di n g t o Healt h I ns ura nce  P orta bilit y a n d Acc o u nta bilit y Act ( HI P A A). 
S u bjects will be i de ntifie d b y c o de n u m bers o n case re p or t f or ms a n d ot her 
d oc u me nts . 
 
2 7)  Pr o visi o ns t o Pr otect t he Pri v ac y I nterests of S u bjects  
Eff orts will be ma de t o li mit t he use a n d discl os ure of pers o nal i nf or mati o n, 
i ncl u di n g researc h st u d y a n d me dical rec or ds, t o pe o ple w h o ha ve a nee d t o re vie w 
t his i nf ormati o n .  T he s p o ns or, m o nit ors, a u dit ors, t he I R B, t he F o o d a n d Dr u g 
A d mi nistrati o n will be gra nte d direct access t o y o ur me dical rec or ds t o c o n d uct a n d 
o versee t he researc h . 

I R B St u d y N u m ber: 2 0 1 4 0 1 2 7 
Versi o n 3, Date: 9/ 2/ 2 0 1 6 
 
 
 
 
Pa ge 1 3 of 1 4  
R e vis e d : M a y 2 6, 2 0 2 0  
 
 
Pri nci pal i n vesti gat or a n d st u d y me m bers will ha ve acces s t o st u d y d oc ume nts. 
D oc u me nts will be sec ure d  i n a cl ose d offic e w here PI a n d st u d y me m bers ha ve 
access. 
2 8)  C o m pe ns ati o n f or Rese arc h -Rel ate d I nj ur y  
 
Patie nts ma y be e x p ose d t o ris k of i nj ur y fr o m partici pati o n i n t his st u d y. If i nj ur y 
occ urs, treat me nt will i n m ost cases be a vaila ble. If patie nts ha ve i ns ura nce, t he 
i ns ura nce c o m pa n y ma y or ma y n ot pa y f or t hese c osts. If t he y d o n ot ha ve 
i ns ura nce, or t he i ns ura nce c o m pa n y ref us es t o pa y, st u d y patie nt s will be e x pecte d 
t o pa y. F u n ds t o c o m pe nsate f or pai n, e x pe nses, l ost wa ges a n d ot her da ma ges 
ca use d b y i nj ur y are n ot a vaila ble.  
 
2 9)  Ec o n o mic B ur de n t o S u bjects  
As t his is a n i n vesti gati o nal st u d y, t here is n o c ost t o s u bjects f or 
partici pati n g, n or will t heir i ns ura nce be bille d f or a n y of t he pr oce d ures 
perf or me d d uri n g t he st u d y. I n t he e ve nt t he a s u bject will re q uire me dical 
treat me nt as a res ult of t heir partici pati o n i n t his st u d y, w hic h is u nf oresee n, 
t heir i ns ura nce c o m pa n y ma y or ma y n ot c o ver t he e x pe nses ass ociate d, a n d 
if t he y ref use t o pa y t he s u bject will be res p o nsi ble f or t he c osts.  
Partici pa nts will be re q uire d t o atte n d 3 wee kl y visits, a n d e n d ure ass ociate d 
e x pe nses wit h tra ns p ortati o n a n d par ki n g i nitiall y, b ut will be offset b y t he 
i nce nti ve gi ve n w he n  c o m pleti n g st u d y visits.  
3 0)  C o nse nt Pr ocess  
 
T his st u d y will be c o n d ucte d i n acc or da nce wit h t he pr o visi o ns of 2 1 C o de of 
Fe deral Re g ulati o ns ( C F R). T he i nf or me d c o nse nt e x plai ns t he pr oce d ures a n d 
re q uire me nts of t he st u d y, t o get her wit h a n y p ote ntial hazar ds/ris ks. Eac h s u bject 
will si g n s uc h a n i nf or me d  c o nse nt f or m or gi ve oral c o nse nt/ pr o x y. T he s u bject 
will be ass ure d of t he free d o m t o wit h dra w fr o m partici pati o n i n t he st u d y at a n y 
ti me. T he I n vesti gat or will retai n t he ori gi nal si g ne d c o nse nt f or m a n d pr o vi de eac h 
s u bject wit h a c o p y of t he si g ne d c o nse nt f or m a n d ma ke s ure t hat t he patie nt 
u n derst o o d t he c o nse nt f or m. 
 
T he i n vesti gat ors will f oll o w “ S O P: I nf or me d C o nse nt Pr ocess f or Researc h ( H R P-
0 9 0).”  
 
3 1)  Pr ocess t o D oc u me nt C o nse nt i n Writi n g  
I n vesti gat ors will be f oll o wi n g “ S O P: Writte n D oc u me ntati o n of C o nse nt 
( H R P- 0 9 1).” C o nse nt F or m attac he d.  

I R B St u d y N u m ber: 2 0 1 4 0 1 2 7 
Versi o n 3, Date: 9/ 2/ 2 0 1 6 
 
 
 
 
Pa ge 1 4 of 1 4  
R e vis e d : M a y 2 6, 2 0 2 0  
 
 
3 2)  Dr u gs or De vices  
 
T he de vices use d f or t D C S a n d T M S ar e F D A a p pr o ve d a n d a vaila ble at t he 
Ne ur o m ot or Re ha bilitati o n Researc h La b orat or y   at t he U ni versit y of Mia mi Miller  
Sc h o ol of Me dici ne Pr ofessi o nal Arts Ce nter ( P A C). O nl y a ut h orize d pers o n nel has 
access t o t he e q ui p me nt a n d will be use d o nl y o n s u bjects a n d be use d o nl y b y 
a ut h orize d i n vesti gat ors.  See attac he d.