Combining Cerebellar tDCS and Constraint-induced Language Therapy in Non-fluent Aphasia: a Novel Approach to Target Discourse
Phase: NA
Conditions: Aphasia, Non-fluent Aphasia, Stroke, Brain Injuries
Sponsor: University of Minnesota

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
PROTOCOL COVER PAGE 
Protocol Title
Combining cerebellar tDCS and constraint-induced language 
therapy in non-ﬂuent aphasia: a novel approach to target 
discourse
Principal 
Inves9gator/Faculty 
Advisor
Name: Sharyl Samargia-Grive=e
Department: Communica>on Sciences and Disorders
Telephone Number: 218-726-8347
Email Address: samargia@d.umn.edu
Student Inves9gator
Name: Madelyn Graham, Haley Evans, and Marie Meyesmbourg
Current Academic Status (Student, Fellow, Resident): 
 Graduate Students
Department: Communica>on Sciences and Disorders
Telephone Number:218-726-8347
Ins>tu>onal Email Address:evan0574@d.umn.edu, 
graha745@d.umn.edu, and meyse016@d.umn.edu
Scien9ﬁc 
Assessment
I believe Scien>ﬁc Assessment is not required.
IND/IDE # (if 
applicable)
N/A
IND/IDE Holder
N/A.
Inves9ga9onal Drug 
Services # (if 
applicable)
N/A.
Version Number/
Date:
Version 5  08/09/2023 
Page  of 
 
Template  Revised On: 11/01/2021
1
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
ANCILLARY REVIEWS 
DO NOT DELETE.  Submit the completed checklist below with your protocol. 
Which ancillary reviews do I need and when do I need them? 
Refer to HRP-309 for more informa>on about these ancillary reviews.
Select yes 
or no
Does your study…
If yes…
Impact on 
IRB 
☐ Yes 
☒ No 
Include Gille=e resources, 
staﬀ or loca>ons
Gille+e Scien/ﬁc review and 
Gille+e Research Administra/on 
approval is required.  Contact: 
research@gille+echildrens.com  
Required 
prior to 
IRB 
submissio
☐ Yes 
☒ No 
Involve Epic, or Fairview 
pa>ents, staﬀ, loca>ons, 
or resources?
The Fairview ancillary review will 
be assigned to your study by IRB 
staﬀ 
Contact:
Approval 
must be 
received 
prior to 
IRB 
commiVe
e/ 
designate
d review.   
Consider 
seeking 
approval 
prior to 
IRB 
submissio
n.
☒ Yes 
☐ No 
Include evalua>on of 
drugs, devices, biologics, 
tobacco, or dietary 
supplements or data 
subject to FDA 
inspec>on?
The regulatory ancillary review 
will be assigned to your study by 
IRB staﬀ 
Contact: medreg@umn.edu  
See: h+ps://policy.umn.edu/
h/ d d
☐ Yes 
☒ No 
Require Scien>ﬁc Review? 
Not sure? See guidance in 
the Inves>gator Manual 
(HRP-103). 
Documenta/on of scien/ﬁc merit 
must be provided.   
Contact: hrpp@umn.edu 
☐ Yes 
☒ No 
Relate to cancer pa>ents, 
cancer treatments, cancer 
screening/preven>on, or 
tobacco?
Complete the CPRC applica/on 
process.  
Contact: ccprc@umn.edu 
☐ Yes 
☒ No 
Include the use of 
radia>on? 
(x-ray imaging, 
radiopharmaceu>cals, 
external beam or 
b
h h
)
Complete the AURPC Human Use 
Applica/on and follow 
instruc/ons on the form for 
submission to the AURPC 
commi+ee. 
b
d
Approval 
from 
these 
commiVe
es must 
be 
received 
prior to 
IRB 
approval;  
☐ Yes 
☒ No 
Use the Center for 
Magne>c Resonance 
Research (CMRR) as a 
study loca>on?
Complete the CMRR pre-IRB 
ancillary review  
Contact: ande2445@umn.edu 
Page  of 
 
Template  Revised On: 11/01/2021
2
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
☐ Yes 
☒ No 
Include the use of 
recombinant or synthe>c 
nucleic acids, toxins, or 
infec>ous agents?
Complete the IBC applica/on via 
eprotocol.umn.edu
pp
These 
groups 
each have 
their own 
applica9o
n process. 
☐ Yes 
☒ No 
Include the use of human 
fetal >ssue, human 
embryos, or embryonic 
stem cells?
Contact OBAO for submission 
instruc/ons and guidance
☒ Yes 
☐ No 
Include PHI or are you 
reques>ng a HIPAA 
waiver?
If yes, HIPCO will conduct a 
review of this protocol. 
Contact: privacy@umn.edu 
☐ Yes 
☒ No 
Use data from CTSI Best 
Prac>ces Integrated 
Informa>cs Core (BPIC)  
Formerly the AHC 
Informa>on Exchange 
( )?
The Informa/on Exchange 
ancillary review will be assigned 
to your study by IRB staﬀ 
Contact: bpic@umn.edu
Approval 
must be 
received 
prior to 
IRB 
approval. 
These 
groups do 
not have 
a 
separate 
applica9o
n process 
but 
addi9onal 
informa9
on from 
the study 
☐ Yes 
☒ No 
Use the Biorepository and 
Laboratory Services to 
collect >ssue for 
research?
The BLS ancillary review will be 
assigned to your study by IRB 
staﬀ. 
Contact: Jenny Pham 
h
d
☐ Yes 
☒ No 
Have a PI or study team 
member with a conﬂict of 
interest?
The CoI ancillary review will be 
assigned to your study by IRB 
staﬀ 
Contact: becca002@umn edu
☒ Yes 
☐ No 
Need to be registered on 
clinicaltrials.gov?
If you select “No” in ETHOS, the 
clinicaltrials.gov ancillary review 
will be assigned to your study by 
IRB staﬀ 
Contact: kmmccorm@umn.edu 
☐ Yes 
☒ No 
Require registra>on in 
OnCore?
If you select “No” or “I Don’t 
Know” in ETHOS, the OnCore 
ancillary review will be assigned 
to your study by IRB staﬀ 
d
Does not 
aﬀect IRB 
approval. 
Page  of 
 
Template  Revised On: 11/01/2021
3
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
REVISION HISTORY 
Revision #
Version Date
Summary of Changes
Consent Change?
2
8/17/22
Added details re: adverse effects in 
section 13.0
Modiﬁed consenting process will 
always be in person, section 21.0
Changed population of “fear of 
negative consequences…” as 
excluded, section 9.0
Deleted “serious health 
conditions…” section in section 9.0
yes
3
8/29/2022
Removed popula>on suscep>ble to 
coercion” 
No
4
12/20/2022
Changed tDCS interven>on from 
cathodal to anodal (per recent 
evidence) and increased the 
behavioral interven>on from 30 
minutes to 45 minutes (per recent 
evidence).  Anodal electrode will be 
placed over right cerebellum, 
cathode electrode will be placed 
over right deltoid (per recent 
evidence re: placement) 
Changed working memory task 
from Wisconsin Card Sorting task 
to N-back task (per recent evidence 
and recommendations from 
colleagues using these tasks)
Students have just finished training 
and we finalized the SOP. 
Recruitment will begin in mid 
January.
No
Page  of 
 
Template  Revised On: 11/01/2021
4
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
5
08/09/2023
Remove history of migraine from 
exclusionary criteria.  
Change “history of seizures” to 
history of seizures within the past 
12 months. 
Conﬁrma>on of non-ﬂuent aphasia 
diagnosis is requested to be 
changed from only physician or 
clinician report or Assessment 
using the Western Aphasia Ba=ery 
to add “informal language 
assessment conducted by the PI”. 
Because PI is a cer>ﬁed, licensed 
speech-language pathologist, 
characteris>cs of non-ﬂuent 
aphasia become apparent during 
the interac>on with the poten>al 
par>cipant through ques>ons and 
answers about the study and 
through the screening process. 
Changes made to protocol (pages 
20-21) and screening form 
No
Page  of 
 
Template  Revised On: 11/01/2021
5
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
Table of Contents 
1.0 
Objec>ves 
8 
2.0 
Background 
8 
3.0 
Study Endpoints/Events/Outcomes 
10 
4.0 
Study Interven>on(s)/Inves>ga>onal Agent(s) 
13 
5.0 
Procedures Involved 
14 
6.0 
Data and Specimen Banking 
19 
7.0 
Sharing of Results with Par>cipants 
19 
7.1 
Sharing Results: 
19 
7.2 
Sharing Gene>c Results: 
19 
8.0 
Study Popula>on 
20 
9.0 
Vulnerable Popula>ons 
21 
10.0 
Local Number of Par>cipants 
23 
11.0 
Local Recruitment Methods 
24 
12.0 
Withdrawal of Par>cipants 
25 
13.0 
Risks to Par>cipants 
26 
14.0 
Poten>al Beneﬁts to Par>cipants 
27 
15.0 
Sta>s>cal Considera>ons 
27 
16.0 
Health Informa>on and Privacy Compliance 
29 
16.1 
Select which of the following is applicable to your research: 
29 
17.0 
Conﬁden>ality 
33 
18.0 
Provisions to Monitor the Data to Ensure the Safety of Par>cipants 
33 
19.0 
Provisions to Protect the Privacy Interests of Par>cipants 
39 
20.0 
Compensa>on for Research-Related Injury 
39 
21.0 
Consent Process 
40 
22.0 
Sejng 
41 
23.0 
Mul>-Site Research 
41 
24.0 
Coordina>ng Center Research 
42 
25.0 
Resources Available 
42 
26.0 
References 
42 
Page  of 
 
Template  Revised On: 11/01/2021
6
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
ABBREVIATIONS/DEFINITIONS 
Anodal Transcranial Direct Current S>mula>on (a-tDCS) 
Constraint-induced language therapy (CILT) 
Dorsolateral Prefrontal Cortex (DLPFC) 
Electroencephalogram (EEG) 
Quality of Life (QOL) 
Speech-Language Pathologist (SLP)  
Transcranial Direct Current S>mula>on (t-DCS) 
Dento-thalamic-cor>cal tract (DTC) 
Func>onal magne>c resonance imaging (fMRI) 
Principal Inves>gator (PI) 
Clinical Transla>onal Research Services (CTRS) 
Biosta>s>cal Design and Analysis Center (BDAC) 
Standard Opera>ng Procedures (SOP) 
Sta>s>cal Package for the Social Sciences (SPSS) 
Stroke and Aphasia Quality of Life Scale (SAQOL) 
Page  of 
 
Template  Revised On: 11/01/2021
7
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
1.
Objec9ves 
1.1. Purpose:  
To determine the eﬀect of combining constraint-induced language therapy 
(CILT) with cerebellar tDCS in individuals with non-ﬂuent aphasia ader 
stroke.  
The primary aims are   to 1) determine the eﬀect of combining cerebellar 
tDCS with constraint-induced language therapy (CILT) on language as 
measured by a verbal ﬂuency task and discourse analysis task in a 
prospec/ve, crossover study of adults with non-ﬂuent aphasia ader a 
cor/cal stroke and 2) demonstrate feasibility and data collec/on to inform a 
larger study. 
The secondary aims include impact of the combined interven/on on 1) 
res/ng state spectral EEG as measured through delta wave percentage 2) 
working memory as measured by the score on the Wisconsin Card Sor/ng 
Test and 3) quality of life as measured by the Stroke Aphasia Quality of Life 
survey tool. A ﬁnal secondary aim will be to iden/fy the tolerance of the 
interven/on and barriers to par/cipa/on measured by the adverse events 
ques/onnaire.  
2.
Background 
2.1. Signiﬁcance of Research Ques>on/Purpose:  
Informa/on gained from this study will drive changes to the methodology 
for a larger clinical trial that will minimize a+ri/on and help determine 
robust outcome measures.  
Non-ﬂuent aphasia occurs ader a focal injury to the expressive language 
regions of the cortex, most oden ader a stroke and is characterized by 
limited verbal language and intact comprehension of language. While 
eﬃcacious behavioral interven/ons have been iden/ﬁed, they are few and 
rarely lead to complete language recovery. The loss of eﬀec/ve, eﬃcient 
expressive language can have a devasta/ng impact on social rela/onships, 
return to work, independence and mental health, to name a few. 
Iden/ﬁca/on of novel, eﬀec/ve interven/ons for non-ﬂuent aphasia has 
been iden/ﬁed as a key research priority in the ﬁeld of speech-language 
pathology. 
Preliminary data will provide valuable informa/on about the poten/al of 
combining CILT with right cerebellar anodal tDCS to posi/vely impact 
language and working memory in non-ﬂuent aphasia. The dento-thalamic-
cor/cal tract (DTC) is the primary pathway between the cerebellum and 
cortex and has recently been implicated in non-ﬂuent aphasia. A be+er 
Page  of 
 
Template  Revised On: 11/01/2021
8
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
understanding of the role of the DTC and its poten/al for neuroplas/c 
change ader cor/cal stroke will be included in the interpreta/on. 
Neurophysiologic data from EEG will reveal not only the impact of tDCS on 
alpha and delta bands but the rela/onship to discourse. Finally, we will be 
able to document changes to quality of life and determine if changes are 
related to the experimental interven/on.   
From an educa/onal perspec/ve, this project will provide a valuable inter-
professional experience for graduate students from the Departments of 
Communica/on Sciences and Disorders and Department of Computer 
Science. Such cross-college collabora/ons are an ins/tu/onal priority on the 
University of Minnesota, Duluth campus. 
This body of work has the poten/al to lead to the development of a new 
interven/on protocol for non-ﬂuent aphasia and provide the 
neurophysiologic ra/onale for the changes observed. Together, this will 
drive the ﬁeld of neurorehabli/a/on forward in crea/ng novel, innova/ve 
interven/ons for op/mal func/onal recovery.  
2.2. Preliminary Data: N/A 
2.3. Exis>ng Literature:  
The study of neuroplas/city has provided much needed insight into 
mechanisms of neural recovery which has launched a shid in the way 
rehabilita/on professionals plan interven/on for individuals ader stroke and 
brain injury. Now, greater a+en/on is given to the type and amount of 
behavioral, task-speciﬁc prac/ce that is thought to promote long-term 
poten/a/on and experience dependent plas/city. However, func/onal 
recovery ader stroke and brain injury is s/ll, oden incomplete, nega/vely 
impac/ng independence and return to social, voca/onal and community 
engagement.  
Intensity of rehabilita/on has been iden/ﬁed as a key research priority by a 
number of authors(Cherney et al., 2008, 2011; Marangolo, 2020). 
Speciﬁcally, CILT reportedly has an 86% evidence to clinical use gap and 
therefore, requires addi/onal study (Shrubsole et al., 2018). 
Another research priority iden/ﬁed by Marangolo and colleagues (2020) 
was to be+er determine the poten/al eﬀects of cerebellar tDCS on language 
in individuals with aphasia.  Many reports have conﬁrmed connec/vity 
between the right cerebellar hemisphere and the led cortex, speciﬁcally the 
frontal and prefrontal cor/cal regions (Stoodley, 2012). These regions are 
Page  of 
 
Template  Revised On: 11/01/2021
9
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
associated with expressive language, motor planning and programming 
and cogni/on. In fact, the right cerebellum has been shown to play a role in 
word retrieval and genera/on, working memory, language learning and 
seman/c processing (Murdoch, 2010; Stoodley, 2012) and diaschesis in the 
right cerebellum has been shown in chronic non-ﬂuent aphasia (Abe et al., 
1997). This, paired with the distance from the stroke lesion site makes the 
right cerebellum a desirable loca/on for s/mula/on.  The combina/on of 
tDCS behavioral language interven/on has resulted in improved naming in 
individuals with aphasia (Sebas/an et al., 2017, 2020; Turkeltaub et al., 
2016). However, there has been no evidence regarding other func/onal 
language skills such as discourse. 
Finally, another research priority has been the inclusion of neurophysiologic 
measures in interven/on studies to be+er understand the neural 
underpinnings of the experimental interven/on (Cherney et al., 2008, 2011). 
Although func/onal magne/c resonance imaging is the tool most oden 
recommended, it has many contraindica/on such as cost, availability, and 
individual comfort and tolerance. Although EEG acquires diﬀerent data than 
fMRI, it is a measure of neurophysiology. It is also non-invasive, more 
accessible and cost-eﬀec/ve, fairly fast to acquire and well-tolerated. 
Res/ng state EEG has been iden/ﬁed as a viable tool to inves/gate 
electrical brain ac/vity in those with post-stroke aphasia (Dalton et al., 
2021) and is sensi/ve to changes ader tDCS (Boonstra et al., 2016). Since an 
increase in delta frequency bands has been associated with the language 
deﬁcits observed in aphasia (Hensel et al., 2004; Spironelli & Angrilli, 2009), 
one would hypothesize it may be a sensi/ve measure to determine the 
neurophysiologic impact of a language interven/on such as that in the 
proposed study. In addi/on, an increased peak alpha frequency has been 
associated with improved a+en/on and “cogni/ve preparedness” which 
would also be an expected outcome of the proposed interven/on.  
This pilot study has the poten/al to inform a larger, externally funded 
clinical trial that may lead to an innova/ve, novel approach to improve 
func/onal language in those with non-ﬂuent aphasia. 
3.
Study Endpoints/Events/Outcomes 
3.1. Primary Endpoint/Event/Outcome:  
Primary outcome variables include:  
1) Main Concept Discourse analysis using standardized picture descrip/on 
“Broken Window”, story retell “Cinderella” and procedural narra/ve “how 
Page 
 of 
 
Template  Revised On: 11/01/2021
10
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
to make a peanut bu+er sandwich”. Each task has established standards 
and a scoring system for responses. Scoring is categorical and includes:  
accurate and complete=3, accurate and incomplete =2, inaccurate and 
complete=2, inaccurate and incomplete =1 and absent response =0 
(Richardson & Dalton, 2016). Hypothesis: We hypothesize the raw score of 
each of the discourse measures (picture, story and procedure) will 
signiﬁcantly increase ader the real tDCS interven/on, but not ader the 
sham interven/on.  
2) Verbal Fluency is assessed by asking the par/cipant to name as many 
animals as they can in one minute and then as many words that start with /
f/ as they can in one minute. The tester collects a tally of how many animals 
and words that begin with /f/ were produced by the par/cipant which is 
used as a raw score, scaled. If the par/cipant names items that are not 
within those categories, those responses are not counted in the tally. These 
tasks are valid and reliable and used throughout aphasia literature. 
Hypothesis: We hypothesize the raw score of the verbal ﬂuency measures 
will signiﬁcantly increase ader the real tDCS interven/on, but not ader the 
sham interven/on.  
These data will be collected at four points in /me:  
1) Ini/al baseline; 
2) post interven/on (A or B); 
3) Follow-up baseline (ader washout period);  
4) post interven/on (A or B)   
3.2. Secondary Endpoint(s)/Event(s)/Outcome(s):  
1. Working memory has been shown to play a role in non-fluent aphasia. 
Working memory is assessed using the N-back task. Scoring is binary and 
each response is either scored as correct=1 or incorrect =0 to obtain a raw 
score that is a scaled variable. We are interested in learning if the working 
memory score changes after intervention and if the change has a relationship 
with any changes in language as measured above in the primary endpoint. 
Hypothesis: We hypothesize the working memory score will signiﬁcantly 
increase ader the real tDCS interven/on, but not ader the sham 
interven/on. We also hypothesize a signiﬁcant posi/ve rela/onship 
between the working memory score and the scores across all three 
discourse tasks. 
These data will be collected at four points in >me:  
1) Ini>al baseline; 
2) Post interven>on (A or B); 
Page 
 of 
 
Template  Revised On: 11/01/2021
11
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
3) Follow-up baseline (aner washout period);  
4) Post interven>on (A or B)   
2. An increase in delta wave percentage during res>ng state EEG has been 
shown in individuals with aphasia. The standard prac>ce is to conduct a 2 
minute res>ng state EEG while eyes are open. Data is then processed 
through EEGLab in MATLab to “pull out” the amount of delta wave bands/
total wave bands to iden>fy a percentage of delta waves within the 2 
minute sample. We are interested in learning if this delta percentage 
changes aner interven>on and if the change may be associated with any 
changes in language as measured above in the primary endpoint. The delta 
wave value is calculated by dividing the number of delta waves present/
total waves within the 2 minute sample and represented in a percentage. 
The delta wave percentage will be calculated for each of the following EEG 
loca>ons: Fp1, F3, F7 and Fz of the 10/20 Interna>onal EEG system. This 
would provide a neurophysiologic ra>onale for the changes in language. 
Hypothesis: We hypothesize the delta percentage to signiﬁcantly decrease 
ader the real tDCS interven/on, but not ader the sham interven/on. We 
also hypothesize a signiﬁcant nega/ve correla/on between the delta 
percentage and scores across the discourse tasks, with lower delta wave 
percentage, language scores will be higher. 
These data will be collected at four points in >me:  
1) Ini>al baseline; 
2) Post interven>on (A or B); 
3) Follow-up baseline (aner washout period);  
4) Post interven>on (A or B)   
3. Quality of Life will be assessed using an abbreviated version of the Stroke 
and Aphasia Quality of Life Scale-39 (SAQOL-39) (Hilari et al., 2003) ), which 
uses a Likert Scale 1-5. Comple>on of the SS-QOL results in a raw score, 
which will be a scaled variable. We are interested in the rela>onship 
between QOL and changes in language as measured above. Hypothesis: We 
hypothesize the raw score of the SAQOL will signiﬁcantly increase ader the 
real tDCS interven/on, but not ader the sham interven/on. We also 
hypothesize the score on the SAQOL will be posi/vely and signiﬁcantly 
correlated with scores across the discourse tasks. 
These data will be collected at four points in >me:  
1) Ini>al baseline; 
2) Post interven>on (A or B); 
3) Follow-up baseline (aner washout period);  
4) Post interven>on (A or B)   
Page 
 of 
 
Template  Revised On: 11/01/2021
12
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
4. An adverse events/experien>al survey will be given to par>cipants to 
provide using a Likert Scale 1-4. In addi>on two open ended ques>ons will 
be asked about posi>ve experiences and nega>ve experiences to help us 
iden>fy barriers to par>cipa>on. The objec>ve por>on will provide us a raw 
score and the open ended ques>ons will be analyzed qualita>vely for 
agreement and themes. This informa>on will be used to hone the 
methodology to improve reten>on and reduce a=ri>on in a larger clinical 
trial. This survey will be provided at the end of the experience. If a 
par>cipant drops out, the research team will reach out to ask the 
par>cipant to complete the survey to assist us in establishing be=er 
methodology. 
4.
Study Interven9on(s)/Inves9ga9onal Agent(s) 
4.1. Descrip>on:  
There will be two interven>on condi>ons in this study: 
1) anodal tDCS (2mA) to the right cerebellum; and  
2) sham tDCS to the right cerebellum.  
The par>cipants will receive 20 minutes of tDCS (sham or real) during 
constraint-induced language therapy (CILT) followed by an addi>onal 20 
minutes of CILT alone.  
tDCS (TCT Research Limited; Hong Kong): 5x5 saline-soaked sponge 
electrodes will be used with the anode placed over the right cerebellar 
hemisphere; 1cm under and 4cm lateral of the inion targe>ng lobule VII 
and the anode will be placed on the right shoulder (Ferrucci et al., 2015; 
Sebas>an et al., 2020). The electrode placement will be the same across 
both condi>ons.  
CILT: The CILT behavioral interven>on will be led by a cer>ﬁed, licensed 
speech-language pathologist and a graduate student assistant and will 
follow the guidelines of CILT (Maher et al., 2006; Mozeiko et al., 2016; 
Pulvermuller et al., 2001). During the behavioral language interven>on, 
par>cipants will engage in language ac>vi>es such as card games that 
require verbal expression. Other forms of communica>on such as gestures 
and wri>ng will be discouraged and only verbal output will be encouraged 
through the use of cues and, when needed, models.  
As this is a within subject study, all par>cipants will experience both 
interven>on condi>ons through a cross over design. Each condi>on will 
Page 
 of 
 
Template  Revised On: 11/01/2021
13
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
involve 12 interven>on sessions across 4 weeks; 3 sessions/week with a 4-
week washout period between condi>ons.  
We believe this study meets the criteria for NSR-IDE because (1) Is not an 
implant and does not present a poten>al for serious risk to the health, 
safety, or welfare of a subject; (2) Is not purported and will not be 
represented to be for use suppor>ng or sustaining human life and presents 
a poten>al for serious risk to the health, safety, or welfare of a subject; (3) 
Will not be used of substan>al importance in diagnosing, curing, mi>ga>ng, 
or trea>ng disease, or otherwise preven>ng impairment of human health 
and does not present a poten>al for serious risk to the health, safety, or 
welfare of a subject; and/or (4) Does not otherwise pose a poten>al for 
serious risk to the health, safety, or welfare of a subject.  
The sponsor-inves>gator agrees to comply with the abbreviated IDE 
requirements in 21 CFR 812.2(b) 
4.2. Drug/Device Handling: N/A 
4.3. Biosafety: N/A 
4.4. Stem Cells: N/A 
4.5. Fetal Tissue: N/A 
5.
Procedures Involved 
5.1. Study Design: 
Within subject, crossover prospec/ve pilot study. 
5.2. Study Procedures:  
Poten/al par/cipants will be recruited through the Robert F. Pierce (RFP)  
Speech-Language and Hearing Clinic on the UMD campus and surrounding 
communi/es including stroke support groups and public adver/sements 
using paper and digital ﬂyers. Digital ﬂyers will also be used as posts to the 
Neural Func/on and Recovery Lab research lab social media page(s) and the 
lab website.  Past and current clients of the RFP Speech-Language and 
Hearing Clinic, with a diagnosis of non-ﬂuent aphasia, will be sent a paper 
ﬂyer in the mail and will be informed of the study by their current graduate 
student clinician. In addi/on, paper ﬂyers will be posted in the lobby of the 
Robert F. Pierce Speech-Language and Hearing Clinic.  
Page 
 of 
 
Template  Revised On: 11/01/2021
14
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
Par/cipants will be screened for eligibility using the screening form (in 
supplementary documents) to ensure they meet the eligibility requirements. 
Screening can be done in person or via phone. The individual must provide 
documenta/on of a led hemisphere stroke in the form of a physician or 
clinician report and diagnosis of non-ﬂuent aphasia in the form of a 
physician or clinical report. If they do not have documenta/on of their 
stroke, we will obtain consent from the interested par/cipant to request the 
medical report. If they do not have documenta/on of their aphasia 
diagnosis and are s/ll interested in par/cipa/ng, we will either obtain a 
consent from the interested par/cipant to request the SLP assessment 
report or the research team will administer the Western Aphasia Ba+ery 
Assessment to determine the type and severity of aphasia.  Once deemed 
eligible, a member of the research team will go over the consent form with 
the individual in person and answer any ques/ons the individual has. Both 
the par/cipant and research team member will sign the consent form to 
cer/fy it and a copy will be provided to the par/cipant. Paper copies will 
then be scanned and stored in Advarra EDC.  If the par/cipant is screened 
through a phone mee/ng or via virtual visit on Zoom, the consent form will 
be discussed and shared with the par/cipant through email. Upon coming 
in for the ﬁrst baseline assessment visit, the consent form will then be 
signed. 
Part of the consent requires par/cipants to not engage in other speech-
language therapy sessions outside of those provided in the study. For 
example, an individual who is currently receiving speech-language therapy 
services at the RFP Clinic who consents and is enrolled in this study would 
then only receive the interven/on visits outlined in this study for the 
dura/on of their enrollment of the study and would then resume speech-
language therapy services at RFP Clinic once their par/cipa/on ends. 
Careful considera/on will be given to those who receive insurance beneﬁts 
that cover speech-language therapy services at other clinics to ensure a 
par/cipant won’t “lose” insurance coverage for stepping away from 
tradi/onal speech-language therapy sessions for a 2-month /me span. This 
is typically only an issue for individuals receiving beneﬁts from Medicare A. 
The PI will talk with poten/al par/cipants regarding this issue. 
Par/cipants will a+end 17 visits over the course of 2 months, including one 
visit for screening and consen/ng process. The screening and consen/ng 
visit is expected to last ~30 minutes. If formal tes/ng is needed for the 
aphasia diagnosis to be conﬁrmed, the screening and consen/ng visit will 
last ~90 minutes. Each assessment/data collec/on visit is expected to last 
60-75 minutes. Interven/on visits are expected to last 60 minutes for total 
Page 
 of 
 
Template  Revised On: 11/01/2021
15
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
of 21.5 hours of par/cipa/on over the course of the study. If a par/cipant 
misses an interven/on session, we will a+empt to make it up during that 
same week of interven/on and reschedule the assessment day. The /ming 
of the assessment day post interven/on is cri/cal as tDCS does not appear 
to have long-las/ng eﬀects. The post interven/on assessment visit would 
have to take place within 1-2 days of the last interven/on day. If 
rescheduling is not an op/on, the total number of interven/on sessions 
a+ended will be noted in the data. However, if 2 sessions have been missed 
within either of the interven/on periods, the par/cipant will need to be re-
enrolled or dropped from the study. Par/cipants will be randomly assigned 
to receive either the real or sham tDCS ﬁrst. 
Schedule of Events 
Table 1. Schedule of Research Ac>vi>es. 
Screen 
/ 
 
Baselin
Interven>o
n A or B
Follow-
Up 1
Washout
Baselin
e 2
Interven>o
n A or B 
Follow-
Up 2
Day/Week
Visit 1
Visit 2 
Any>m
e aner 
consent
Visits 3-8 
6 total 
sessions: 3 
sessions 
per week 
across 2 
weeks). 
Must 
occur 
h
Visit 9 
must 
occur 
within 1 
day of 
visit 8
 4 weeks
Visit 10 
can 
occur 
any>m
e aner 
the 4 
week 
washo
ut
Visits 11-16  
6 total 
sessions: 3 
sessions 
per week 
across 2 
weeks 
Must occur 
within 5 
d
f
Visit 17 
must 
occur 
within 1 
day of 
visit 16
Screen for 
Eligibility
x
Consen>ng 
Process
x
Western 
Aphasia 
Ba=ery 
If 
needed
Page 
 of 
 
Template  Revised On: 11/01/2021
16
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
Data Collec/on / Assessment Sessions:  
Par/cipants will be seated comfortably in a chair or in their wheelchair with 
an adjustable table in front of them. A member of the research team will sit 
directly across from the par/cipant and present assessment s/muli for the 
discourse analysis. Discourse analysis will take approximately 15 minutes 
and will include picture descrip/on, story retell and a procedural narra/on. 
The verbal ﬂuency test involves naming as many animals as they can in one 
minute followed by naming as many words star/ng with /f/ as they can 
name in one minute. The total /me for the verbal ﬂuency task is <5 minutes. 
N-back will be given using the laboratory computer and takes 
approximately 10 minutes to complete. These tasks will be videotaped for 
the purposes of accurate data collec/on of par/cipant verbal responses. 
This is necessary for accurate data collec/on as mild forms of aphasia are harder 
to assess in real /me and may require careful examina/on of a video. All 
recordings will be made using Zoom and stored in UMN Box. All temporary ﬁles 
Urine 
Pregnancy 
Test
Only if 
within 
child-
bearing  
years
Discourse 
Analysis 
k
X
X
X
X
Verbal 
Fluency 
k
X
X
X
X
N-back 
(working 
memory)
X
X
X
X
Res>ng 
state EEG 
k
X
X
X
X
Stroke-
Aphasia 
Quality of 
Life Survey
X
X
X
X
Adverse 
Events 
X
X
X
X
Sham OR 
Real 
tDCS+CILT 
X
X
Page 
 of 
 
Template  Revised On: 11/01/2021
17
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
will be immediately deleted once uploaded to Box. Ader the behavioral 
assessments have been completed, the par/cipant’s head will be measured 
and ﬁt with the EEG cap and electrodes (~15 minutes) and three 2-minute 
res/ng state EEG (eyes open) will be done. Finally, the par/cipant will be 
given the SAQOL ques/onnaire with as much assistance is needed for 
reading and/or interpre/ng the meaning of ques/ons. A visual Likert scale 
will be provided as a support for language if need be. The par/cipant will be 
oﬀered breaks between tasks as needed. The research team ran a trial data 
collec/on session with one of the members of the research team who 
provides responses similar to that we would expect of an individual with 
non-ﬂuent aphasia. The data collec/on session lasted 75 minutes. One 
graduate student will be running the EEG por/on of the experiment and has 
been trained and has shown competence in placement of electrode cap and 
use of the EEG data sodware. One graduate student will be running the 
language por/on of the experiment and has been trained and has shown 
competence in the administra/on and scoring of the discourse, ﬂuency and 
working memory tasks.  
Interven>on Sessions:  
Par/cipants will be seated comfortably in a chair with armrests during both 
the interven/on and assessment visits. The assessment and interven/on 
tasks can also be conducted while seated in a wheelchair if need be. Skin 
where the tDCS electrodes will be placed will be gently cleaned using an 
alcohol swab and hair will be separated and clipped to allow the electrode 
to be placed. Two saline-soaked t-DCS sponge electrodes (25 cm2) will be 
used. The anode placed over the right cerebellar hemisphere, 1-2cm below 
the inion and 3-4cm lateral to the inion (Ferrucci et al., 2015; Grimaldi et al., 
2016) and the cathode electrode will be placed on the right deltoid region. 
Electrodes will be kept in place with the neoprene/Velcro head band in the 
tDCS device kit.  The device will be programmed for “real” or “sham” sewng 
for a 20-minute dura/on using the sewng bu+ons on the device.  If the 
device is programmed for “real” tDCS, the intensity will gradually increase 
over the ﬁrst 30-45 seconds to the designated value of 2mA and remain at 
that sewng un/l it gradually decreases in intensity over the last 30-45 
seconds of the 20-minute dura/on. If “sham” is selected, the gradual ramp 
up occurs followed by the ramp down. Therefore, no s/mula/on is provided 
during sham condi/on. While the PI is placing the electrodes, the graduate 
intern will be sewng up the behavioral language ac/vity (CILT) for the 
session. Once the electrodes are in place, the device is programmed and the 
behavioral ac/vity is set up, the interven/on will begin. The tDCS device will 
be turned on (to either real or sham) and the par/cipant will engage in the 
Page 
 of 
 
Template  Revised On: 11/01/2021
18
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
behavioral interven/on. The total interven/on session will last for 45 
minutes: 20 minutes of combined c-tDCS and CILT and the ﬁnal 25 minutes 
CILT only. Ader each interven/on phase, the par/cipant will be asked to 
complete a short adverse eﬀects survey which will help the research team 
make modiﬁca/ons for a larger clinical trial. The research team ran a trial 
interven/on session with one of the members of the research team who 
provides responses similar to that we would expect of an individual with 
non-ﬂuent aphasia. The interven/on session lasted 60 minutes including 
placing and removing of electrodes. All members of the research team will 
be trained in the methods of placing electrodes and demonstrate 
competence. However, for this study, the PI will do all of the electrode 
placement. The placement of the electrodes for cerebellar s/mula/on is 
well described in the literature. For a larger clinical trial, inter-rater 
reliability for electrode placement will be done in order to ensure 
consistency among research staﬀ. 
5.3. Study Dura>on:  
Each interven/on session will be scheduled for 60 minutes to allow for set 
up, take down and ques/ons from the par/cipant.  Each condi/on (Sham 
and Real tDCS) will consist of 6 interven/on visits (3x/week across 2 weeks) 
with a 4-week washout period between condi/ons. Ader the washout 
period, the par/cipant will then engage in 6 interven/on visits of the 
opposite interven/on.  The interven/on visits do not have to be consecu/ve 
within the interven/on week. 
The total dura/on of par/cipant par/cipa/on will be 17 visits across 2 
months. The dura/on an/cipated to enroll all study par/cipants is expected 
to be 18 months. It is an/cipated that it will take 36 months to complete all 
study procedures including data analysis. 
5.4. Individually Iden>ﬁable Health Informa>on:  
Name, date of birth, medical diagnosis (cor/cal stroke) and communica/on 
diagnosis (type of aphasia) will be collected from the par/cipant and 
records provided by the par/cipant (speciﬁcally, the speech-language 
pathologist report). 
5.5. Use of radia>on: N/A 
5.6. Use of Center for Magne>c Resonance Research:  N/A 
Page 
 of 
 
Template  Revised On: 11/01/2021
19
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
6.
Data and Specimen Banking 
6.1. Storage and Access: N/A 
6.2. Data: N/A 
6.3. Release/Sharing: N/A 
7.
Sharing of Results with Par9cipants 
7.1. Sharing Results:  A brief summary of study results will be shared with each 
par>cipant upon comple>on of the study along with a “Thank you” note for 
their par>cipa>on (See thank you le=er in supplemental documents). 
7.2. Sharing Gene>c Results: N/A 
7.2.1 Disclosure of Results: N/A 
7.2.2 Returning Results to Par>cipants: N/A 
Aggregate or individual results: N/A 
  
Laboratory results: N/A 
Plan for return of results to par>cipants: N/A 
Types of results to be returned to par>cipants: N/A 
7.2.3 Future analysis of genotypes: N/A 
8.
Study Popula9on 
8.1. Inclusion Criteria:  
Eligible par/cipants must be over the age of 18 years, have a history of 
stroke and diagnosed with non-ﬂuent aphasia. The individual can provide 
documenta/on of aphasia in the form of a physician or clinician report. If 
they do not have documenta/on of their  their aphasia diagnosis, we will 
either obtain a consent from the interested par/cipant to request the 
speech-language pathology assessment report, the PI can conduct an 
informal language assessment to conﬁrm the diagnosis. Or, if it s/ll unclear, 
Page 
 of 
 
Template  Revised On: 11/01/2021
20
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
the PI will administer the Western Aphasia Ba+ery Assessment to determine 
the type and severity of aphasia.  
In addi/on, eligible par/cipants must be able to independently understand 
simple direc/ons, use some speech to communicate, have access to reliable 
transporta/on (including taxi and/or other transporta/on services), ﬂuent in 
English. 
8.2. Exclusion Criteria:  
Pregnancy, history of seizures within the past 12 months, any metal 
implants in the body such as pacemaker, cochlear implant, aneurysm coil 
or clip (excluding dental ﬁllings), , psoriasis or eczema aﬀec/ng the scalp, 
history of a head injury such as a concussion or diagnosis of a mental 
health or neurological condi/on/disease.  
8.3. Screening:  
The screening process will involve the research staﬀ asking screening 
ques/ons of the poten/al par/cipant (screening form is in supplemental 
documents). This can be done either by phone, virtual visit or in-person 
(screening phone script is in supplemental documents). If the individual 
does not have documenta/on of an aphasia diagnosis, the PI, who is a 
licensed, cer/ﬁed and experienced speech-language pathologist will 
conduct an informal assessment through conversa/on and simple language 
tasks to ensure the diagnosis of non-ﬂuent aphasia. If the diagnosis is s/ll 
unclear, the PI will conduct the Western Aphasia Ba+ery either through an 
in-person visit or via virtual visit to conﬁrm the diagnosis of non-ﬂuent 
aphasia. If the research staﬀ member is a graduate student, they will be 
supervised by the PI, who is a licensed and cer/ﬁed speech-language 
pathologist. Graduate students in speech-language pathology programs are 
qualiﬁed to administer and interpret this test under the supervision/
guidance of a licensed, cer/ﬁed speech-language pathologist. If the 
par/cipant is within child-bearing years, a urine pregnancy test will be 
provided during the ﬁrst in-person visit prior to consen/ng.  
9.
Vulnerable Popula9ons 
9.1. Vulnerable Popula>ons:  
Page 
 of 
 
Template  Revised On: 11/01/2021
21
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
Popula>on / Group
Iden>fy whether any of the 
following popula>ons will be the 
focus of the research (targeted), 
included  but not the focus of the 
research excluded from 
par>cipa>on in the study. 
Children
Excluded
Pregnant women/fetuses/neonates
Excluded
Prisoners
Adults lacking capacity to consent 
and/or adults with diminished 
capacity to consent, including, but 
not limited to, those with acute 
medical condi>ons, psychiatric 
disorders, neurologic disorders, 
developmental disorders, and 
behavioral disorders
Non-English speakers
Those unable to read (illiterate)
Employees of the researcher
Students of the researcher
Undervalued or disenfranchised 
social group
Ac>ve members of the military 
(service members), DoD personnel 
(including civilian employees)
Individual or group that is 
approached for par>cipa>on in 
research during a stressful situa>on 
such as emergency room sejng, 
childbirth (labor), etc.
Individual or group that is 
disadvantaged in the distribu>on of 
social goods and services such as 
income, housing, or healthcare.
Page 
 of 
 
Template  Revised On: 11/01/2021
22
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
9.2. Addi>onal safeguards, if any, to ensure inclusion is appropriate:  
Active members of the military (service members), DoD personnel (including 
civilian employees): Members of the military may not be known, research staff 
will not be asking a direct question about military status to potential participants. 
We do not anticipate vulnerability for this group to be increased by participating 
in this study.  
Undervalued or disadvantaged social group: Undervalued or disadvantaged 
people may not be known, research staff will not be asking a direct question about 
socioeconomic status to potential participants. We do not anticipate vulnerability 
for this group to be increased by participating in this study. 
Individual or group that is disadvantaged in the distribution of social goods 
and services such as income, housing, or healthcare: Undervalued or 
disadvantaged people may not be known, research staff will not be asking a direct 
question about socioeconomic status to potential participants. However, we have 
taken special precaution to make sure participants are fairly and adequately 
compensated for their time in this study, yet not coerced by unreasonably high 
compensation amounts. 
 
Individual or group with a serious 
health condi>on for which there are 
no sa>sfactory standard treatments.
Individual or group with a fear of 
nega>ve consequences for not 
par>cipa>ng in the research (e.g. 
ins>tu>onaliza>on, deporta>on, 
disclosure of s>gma>zing behavior).
Any other circumstance/dynamic 
that could increase vulnerability to 
coercion or exploita>on that might 
inﬂuence consent to research or 
decision to con>nue in research.
Page 
 of 
 
Template  Revised On: 11/01/2021
23
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
9.3. If research holds prospect for direct beneﬁt to par>cipants, provide 
jus>ﬁca>on for any exclusions indicated in the table above: 
Eﬀects of any non-invasive brain s/mula/on technique on an unborn infant 
is unknown, therefore women who are pregnant are excluded from any 
study involving these techniques. In order to complete the language and 
working memory tasks required, individuals must be ﬂuent in English and be 
able to read. There are currently no norma/ve data for these tasks in other 
languages. Individuals with serious health condi/ons will be excluded from 
the pilot due to the number of visits required for the study as individuals 
from this groups may not be able to consistently a+end and/or complete 
the required number of visits. However, a larger clinical trial could oﬀer the 
interven/on sessions in the individual’s home, requiring the par/cipants to 
only come in for the data collec/on/assessment sessions. At that /me, this 
popula/on will not be excluded.  
10.
Local Number of Par9cipants 
10.1. Local Number of Par>cipants to be Consented: A total of 5 par/cipants will 
be enrolled with the goal of 3 par/cipants to complete the dura/on of this 
pilot study. 
11.
Local Recruitment Methods 
11.1. Recruitment Process:  
Paper ﬂyers will be available in the Robert F. Pierce (RFP) Speech-Language and 
Hearing Clinic on the UMD campus. In addi/on, a poster of the ﬂyer will be 
posted in the lobby of the clinic. The ﬂyers (and poster) will have contact 
informa/on for the research team, both email and phone. Interested individuals 
can contact the research staﬀ for more informa/on. The research staﬀ will also 
request permission from the client to come into one of their speech-language 
therapy sessions at RFP to talk with them about the study to gauge their interest.  
Flyers (paper and digital) will also be shared with local support groups, speech-
language pathologists working in medical sewngs who are alumni of the UMD 
master’s program, local medical community and other sources including speech-
language pathology community plaxorms. The research team will reach out to 
local stroke support groups to inform them of the study and request to a+end a 
mee/ng to share informa/on about the study with members of the support 
group. 
Page 
 of 
 
Template  Revised On: 11/01/2021
24
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
To minimize a+ri/on, a “Welcome Packet” will be provided to each par/cipant 
including an individual schedule of each visit, contact informa/on for the 
research staﬀ, transporta/on scheduling informa/on (if needed). Research staﬀ 
will oﬀer to assist in making transporta/on arrangements if needed. Weekend 
and evening visits can be scheduled to accommodate the par/cipants’ schedules 
as some may need to have a caregiver a+end the sessions with them due to 
physical limita/ons, inability to drive, etc. The par/cipant will be asked their 
preference re: communica/ng with the research team. The team will then provide 
regular updates and reminders through that preferred communica/on method 
(phone, text, email). During the interven/on phases, the research team will be in 
daily contact with the par/cipant to check in, conﬁrm transporta/on and answer 
ques/ons.  
If the par/cipant is already an RFP client, the study visits will take the place of 
their regularly scheduled clinic visits at RFP. Breaks will be oﬀered both during 
assessment/data collec/on days and interven/on days as needed with the 
excep/on of the tDCS applica/on. Once the s/mula/on begins, ideally it should 
be provided without a break for that 20 minutes. If an individual expresses 
discomfort, addi/onal saline solu/on is applied to the electrodes. If the individual 
con/nues to express discomfort, the tDCS will stop. The research team does not 
an/cipate this as very few adverse eﬀects have been reported using tDCS. Bo+led 
water and light cookies/crackers will be available to the par/cipant.  
11.2. Iden>ﬁca>on of Poten>al Par>cipants:  
Interested individuals will contact research staﬀ either through email or 
phone. Or, in person, if they are clients in the RFP Clinic. 
11.3. Recruitment Materials:  
Poten/al par/cipants will be recruited through the Robert F. Pierce Speech-
Language and Hearing Clinic on the UMD campus and surrounding communi/es 
including stroke support groups and public adver/sements using paper and 
digital ﬂyers. Digital ﬂyers will also be used as posts to the Neural Func/on and 
Recovery Lab research lab social media page(s) and the lab website.  Past and 
current clients of the RFP Speech-Language and Hearing Clinic, with a diagnosis 
of non-ﬂuent aphasia, will be sent a paper ﬂyer in the mail and will be informed 
of the study by their current graduate student clinician. In addi/on, paper ﬂyers 
will be posted in the lobby of the Robert F. Pierce Speech-Language and Hearing 
Clinic. 
Page 
 of 
 
Template  Revised On: 11/01/2021
25
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
11.4. Payment:  
Par/cipants will receive $150 at the end of the ﬁrst interven/on phase, 
another $150 at the end of the second interven/on phase and a $150 bonus 
for comple/on of the study. Par/cipants will be required to sign a log each 
/me payment is received. Payment will be in the form of adding money to a 
ClingCard given to the par/cipant. 
12.
Withdrawal of Par9cipants 
12.1. Withdrawal Circumstances:  
Par/cipants are free to withdraw from par/cipa/on in the study at any /me 
upon request. An inves/gator may discon/nue or withdraw a par/cipant 
from the study for the following reasons: 
•
Pregnancy 
•
Signiﬁcant study non-compliance 
•
If any clinical adverse event (AE) or other medical condi/on or 
situa/on occurs such that con/nued par/cipa/on in the study would 
not be in the best interest of the par/cipant 
•
If the par/cipant meets an exclusion criterion (either newly 
developed or not previously recognized) that precludes further study 
par/cipa/on 
12.2. Withdrawal Procedures:  
If a par/cipant wishes to withdraw or we determine that the par/cipant should 
withdraw, we will terminate data collec/on and discuss with the par/cipant the 
reasons for withdrawal. All data collected up to that point will be used in analysis 
unless the par/cipant wishes for their data not to be used.  
12.3. Termina>on Procedures:  
This study may be temporarily suspended or prematurely terminated if there is 
suﬃcient reasonable cause. Wri+en no/ﬁca/on, documen/ng the reason for 
study suspension or termina/on, will be provided by the suspending or 
termina/ng party to the PI, IND/IDE sponsor and regulatory authori/es. If the 
study is prematurely terminated or suspended, the PI will promptly inform the IRB 
and will provide the reason(s) for the termina/on or suspension. The study team 
will no/fy the par/cipants of the study termina/on.  
Page 
 of 
 
Template  Revised On: 11/01/2021
26
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
13.
Risks to Par9cipants 
13.1. Foreseeable Risks:  There is a possibility that some par/cipants may face 
fa/gue, embarrassment, frustra/on, or other challenges by par/cipa/ng in 
the study. Par/cipants will be encouraged to take breaks to mi/gate these 
experiences. Par/cipants will also be reminded that par/cipa/on in the 
study is voluntary and as such, they are not required to complete any 
components of the study and may skip ques/ons or assessments en/rely. 
Reports of /ngling/itching sensa/on under the electrode is the most 
commonly reported adverse eﬀect (Nitsche 2008, Table 1). Although there 
have been reports of skin burn at the electrode site ader tDCS, these cases 
were not following safety guidelines and occurred due to extended 
s/mula/on periods of 30 minutes, drying of electrode, abrading skin 
surface prior to s/mula/on and using tap water to soak the electrodes 
When tDCS is used in line with safety guidelines, such as this study 
proposes, using saline soaked electrodes, keeping electrodes soaked well, 
20 minute s/mula/on /me, no burns or hea/ng of the electrodes or scalp 
were avoided. For review, see (Antal et al., 2017; Matsumoto & Ugawa, 
2017) Although the tDCS current is well below threshold of /ssue damage, 
individuals post stroke are more likely to have seizures. Therefore, the 
majority of tDCS safety protocols exclude anyone who has had a history of 
seizures as an addi/onal safeguard. For review, see (Antal et al., 2017; 
Matsumoto & Ugawa, 2017). In addi/on, although no nega/ve eﬀects have 
been observed from tDCS in women who are pregnant or the fetus, there is 
too li+le evidence and most protocols exclude this popula/on un/l more is 
known or un/l the beneﬁts to the pa/ent outweigh the poten/al risk (Antal 
et al., 2017). The electroencephalogram (EEG) is collec/ng data from the 
brain, not s/mula/ng it, therefore, far fewer, if any risks are associated with 
EEG. Previously, EEG electrodes had to be placed by abrading the skin and 
using an adhesive to a+ach them which oden led to risk of infec/on (Ferree 
et al., 2001). However, there are now saline soaked electrodes which do not 
need to be adhered to the skin such as those used in this protocol that have 
similar impedance values of the more “tradi/onal electrodes” (Ferree et al., 
2001). 
Privacy/Conﬁden7ality Risks: Risk of loss of conﬁden/ality is unlikely, but 
could possibly occur as PHI is u/lized as part of this study. This risk would be 
minimized by protec/ons such as de-iden/ﬁca/on of par/cipants via use of 
a study iden/ﬁer, locked/secured/limited access to PHI, and electronic data 
securely stored and password-protected. See also adverse events in 18.2 
Page 
 of 
 
Template  Revised On: 11/01/2021
27
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
13.2. Reproduc>on Risks: Although there have been no adverse side eﬀects of 
tDCS to women who are pregnant, all neuromodula/on studies exclude this 
popula/on due to unknown impact to an unborn baby. 
13.3. Risks to Others: N/A 
14.
Poten9al Beneﬁts to Par9cipants 
14.1. Poten>al Beneﬁts:  
There is a poten/al for a transient improvement in language expression and 
working memory ader par/cipa/ng in the study. 
15.
Sta9s9cal Considera9ons 
15.1. Data Analysis Plan:  
All data will be de-iden/ﬁed and entered into Excel and SPSS for analysis. Visual 
analysis will be conducted ini/ally with plowng of descrip/ve sta/s/cs.  
15.2. Power Analysis: 
A literature review of studies measuring the impact of cerebellar tDCS in aphasia 
did not ﬁnd usable es/mates of varia/on (SD, SEM, IQR, etc.) for the outcomes of 
interest. Accordingly, using a standard eﬀect size scale (Cohen’s d, scaling the 
treatment eﬀect size rela/ve to between-par/cipant SD), and a range of plausible 
within-par/cipant correla/ons of +0.4 to +0.9, we es/mate that enrolling 4 
par/cipants will provide 80% power to detect large (d=0.9) to very large (d=2.3) 
treatment eﬀect sizes using a two-sided 5% signiﬁcance level. 
A post-hoc power analysis will be conducted using the informa/on gathered in 
the pilot study to determine the sample size needed for a larger study.  
15.3. Sta>s>cal Analysis: 
 BDAC was consulted regarding the plan for sta/s/cal analysis. 
Based on their recommenda/ons, the following plan was created. 
Throughout the project, BDAC will be consulted to review this 
sta/s/cal analysis plan and provide addi/onal insight to alterna/ve 
sta/s/cal processes best suited for the data as needed. 
• The quan/ta/ve data for a+ri/on rate and adverse events will be 
descrip/ve in nature and will be reported as counts and rates. The 
Page 
 of 
 
Template  Revised On: 11/01/2021
28
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
open-ended ques/ons regarding barriers to par/cipa/on will be 
analyzed to iden/fy common themes. 
• Primary outcome measures, main concept discourse scores and verbal 
ﬂuency counts, will be compared between treatment condi/ons using mixed 
eﬀects generalized linear models, with ﬁxed eﬀects for treatment, period, 
sequence, pre-post /me point, and treatment by pre-post /me point 
interac/on, and random eﬀects for par/cipant within sequence. This will 
provide diﬀerence-in-diﬀerences (post-treatment minus pre-treatment) 
es/mates for the treatment eﬀect which will be reported along with 95% 
conﬁdence intervals as a measure of precision. Similar models will be used 
to analyze the secondary outcome measures including WI card sor/ng task, 
EEG delta wave, and SAQOLL.  
• Es/mates from these models will provide important informa/on for 
planning a well-powered clinical trial that are not obtainable elsewhere.  
Es/mates that will be gathered in this pilot trial that will inform the 
subsequent power calcula/on include the treatment eﬀect size, within-
par/cipant correla/on of repeated measures, and random eﬀects variance, 
for each of the outcome measures. 
• Pearson’s Correla/on will be conducted to determine the rela/onship 
between primary outcome variables (discourse and working memory 
scores) and SS-QOL as well as other scaled demographic variables such as 
age and dura/on since stroke.  
• Spearman’s Rho Correla/on analyses will be conducted to determine the 
rela/onships between primary outcome variables (discourse and working 
memory) and EEG data, reported in percentage.  
• The mul/variate repeated measures and correla/on analyses may not be 
terribly informa/ve as the pilot sample size may lack the power for these 
sta/s/cs. However, they may be useful in descrip/ve interpreta/on of the 
data and lay the founda/on for the larger clinical trial.   
15.4. Data Integrity: 
Data collec/on is the responsibility of the research team under the 
supervision of the PI. The inves/gator is responsible for ensuring the 
accuracy, completeness, legibility, and /meliness of the data reported. All 
research staﬀ will have extensive training in the procedures of data 
collec/on by following the Standard Opera/ng Procedures for the study. 
Behavioral data (scores on discourse tasks, Wisconsin Card Sor/ng, verbal 
ﬂuency) will be collected on a paper data form (see supplemental 
Page 
 of 
 
Template  Revised On: 11/01/2021
29
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
documents), using par/cipant code. The EEG data will be stored within 
MatLab, again using par/cipant code.  Data will then be entered into a de-
iden/ﬁed excel document stored UMN Secure Box and transferred into an 
SPSS ﬁle when preparing for sta/s/cal analysis. The SPSS ﬁles will also be 
deiden/ﬁed. The de-iden/ﬁed excel and SPSS ﬁles will be stored in UMN 
secure Box folder. All IRB approved research staﬀ will have access to these 
ﬁles in Box. The master database of par/cipant names and codes will be 
kept in a digital ﬁle in UMN secure Box folder as well. IRB approved research 
staﬀ will have access to this ﬁle as well. If research staﬀ changes, ie: 
graduate student completes program and is transi/oned oﬀ of the research 
team, they will be removed from the shared folder.  
16.
Health Informa9on and Privacy Compliance 
16.1.
Select which of the following is applicable to your research: 
☐ My research does not require access to individual health informa>on.   
X I am reques>ng that all research par>cipants sign a HIPCO approved 
HIPAA 
Disclosure Authoriza>on to par>cipate in the research (either the 
standalone form or the combined consent and HIPAA Authoriza>on). 
☐ I am reques>ng the IRB to approve a Waiver or an altera>on of 
research par>cipant authoriza>on to par>cipate in the research. 
Appropriate Use for Research:  
 
 
16.2.
Iden>fy the source of Private Health Informa>on you will be using for 
your research (Check all that apply)   
☐ I will use the Informa>cs Consul>ng Services (ICS) available through 
CTSI (also referred to as the University's Informa>on Exchange (IE) or 
data shelter) to pull records for me 
X I will collect informa>on directly from research par>cipants. 
☐ I will use University services to access and retrieve records from the 
Bone Marrow Transplant (BMPT) database, also known as the HSCT 
(Hematopoie>c Stem Cell Transplant) database. 
☐ I will pull records directly from EPIC. 
☐ I will retrieve record directly from axiUm / MiPACS 
Page 
 of 
 
Template  Revised On: 11/01/2021
30
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
☐ I will receive data from the Center for Medicare/Medicaid Services  
☐ I will receive a limited data set from another ins>tu>on  
☐ Other.  Describe:  
16.3.
Explain how you will ensure that only records of pa>ents who have 
agreed to have their informa>on used for research will be reviewed. 
All par/cipants in this study will consent and sign a HIPAA authoriza/on. 
Data will be collected directly from said par/cipants with no review of 
their medical records. 
16.4.
Approximate number of records required for review:  5 
16.5.
Please describe how you will communicate with research par>cipants 
during the course of this research.  Check all applicable boxes 
☐ This research involves record review only. There will be no 
communica>on with research par>cipants. 
☐ Communica>on with research par>cipants will take place in the course 
of treatment, through MyChart, or other similar forms of 
communica>on used with pa>ents receiving treatment.  
X Communica>on with research par>cipants will take place outside of 
treatment sejngs. If this box is selected, please describe the type of 
communica>on and how it will be received by par>cipants.  
We will communicate with par/cipants via: proofpoint secure emails, 
telephone (using study-speciﬁc phone number), text message (if par/cipant 
agrees by signing the consent for text message correspondence), unsecure 
email (if the par/cipant agrees by signing the consent for unsecure email 
correspondence). 
16.6.
Explain how the research team has legi>mate access to pa>ents/poten>al 
par>cipants: 
16.7.
Loca>on(s) of storage, sharing and analysis of research data, including any 
links to research data (check all that apply).   
☐ In the data shelter of the Informa>on Exchange (IE)  
 
☐ Store 
☐ Analyze 
☐ Share 
☐ In the Bone Marrow Transplant (BMT) database, also known as the 
HSCT (Hematopoie>c Stem Cell Transplant) Database  
 
☐ Store 
☐ Analyze 
☐ Share 
Page 
 of 
 
Template  Revised On: 11/01/2021
31
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
☐ In REDCap (recap.ahc.umn.edu)  
 ☐ Store 
☐ Analyze 
☐ Share 
☐ In Qualtrics (qualtrics.umn.edu) 
 ☐ Store 
☐ Analyze 
☐ Share 
☐ In OnCore (oncore.umn.edu)  
 ☐ Store 
☐ Analyze 
☐ Share 
X In the University’s Box Secure Storage (box.umn.edu) 
 X Store 
☐ Analyze 
X Share 
☐ In an AHC-IS supported server. Provide folder path, loca>on of server and 
IT Support Contact: 
 ☐ Store 
☐ Analyze 
☐ Share 
☐ In an AHC-IS supported desktop or laptop.  
Provide UMN device numbers of all devices: 
 ☐ Store 
☐ Analyze 
☐ Share 
☐ Other: 
Indicate if data will be collected, downloaded, accessed, shared or stored 
using a server, desktop, laptop, external drive or mobile device (including a 
tablet computer such as an iPad or a smartorm (iPhone or Android 
devices) that you have not already iden>ﬁed in the preceding ques>ons 
☐I will use a server not previously listed to collect/download research data 
☐I will use a desktop or laptop not previously listed 
☐I will use an external hard drive or USB drive (“ﬂash” or “thumb” drives) 
not previously listed  
☐I will use a mobile device such as a tablet or smartphone not previously 
listed 
16.8. Consultants. Vendors. Third Par>es: N/A 
16.9. Links to iden>ﬁable data:  
All data will be iden/ﬁed with an iden/ﬁca/on code unique to the 
par/cipant. Study staﬀ will keep the mapping of iden/ﬁca/on code to the 
Page 
 of 
 
Template  Revised On: 11/01/2021
32
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
iden/ty of the par/cipant on an encrypted password protected computer 
stored separately from the data in Box. That same iden/ﬁca/on code will 
be used for data-entry into Box. Any internal data reports will use only these 
codes and will not use any iden/ﬁable informa/on. Any external data 
reports, abstracts, publica/ons, presenta/ons, etc. will present de-
iden/ﬁed, grouped, and/or aggregate data. Any reports to the University of 
Minnesota IRB (such as Adverse Event repor/ng and annual renewal 
reports) will be kept conﬁden/al; they will not include par/cipant- 
iden/ﬁable informa/on; only the par/cipant’s iden/ﬁca/on code will be 
used.
16.10.Sharing of Data with Research Team Members: 
Only IRB-approved members of the study team will have access to the data. 
Data will be shared through UMN Secure Box. 
16.11. Storage of Documents: 
Paper documents will be stored in a locked cabinet in a locked research 
oﬃce only accessible to research staﬀ. 
16.12. Disposal of Documents:  
Disposal of all study documents will be in accordance with the university 
policy. 
17.
Conﬁden9ality 
17.1. Data Security: 
All data will be securely stored in UMN Secure Box. De-iden/ﬁed data in the form 
of an excel data spreadsheet and SPSS data ﬁle will be securely stored in Box. The 
informed consent will NOT be placed in the par/cipant’s medical ﬁle or clinic ﬁle 
(if a client in the RFP Speech-Language Hearing Clinic). 
18.
Provisions to Monitor the Data to Ensure the Safety of Par9cipants 
18.1. Data Integrity Monitoring.  
The sponsor-inves/gator will permit direct access to the study monitors and 
appropriate regulatory authori/es to the study data and to the 
corresponding source data and documents to verify the accuracy of these 
data. 
Page 
 of 
 
Template  Revised On: 11/01/2021
33
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
Independent monitoring of the clinical study for clinical protocol compliance will 
be conducted by University of Minnesota’s Clinical and Transla/onal Science 
Ins/tute (CTSI) clinical trial monitoring service. 
The CTSI monitors will conﬁrm that study ac/vi/es are in compliance with the 
approved protocol and applicable regulatory authori/es (FDA, IRB, local and 
State regula/ons). 
Frequency of monitoring visits will occur: 
·         Ader IRB approval 
·         As soon as possible ader the ﬁrst subject is enrolled 
·         During the study data collec/on phase 
·         Ader the last subject has completed his/her par/cipa/on in the study 
This monitoring schedule may be revised based on the following considera/ons: 
·         Accrual rate 
·         Protocol devia/ons or non-compliance with regulatory authori/es 
·         Magnitude of data correc/ons required 
·         Study stage (e.g. start-up or follow-up) 
·         Complexity of the trial 
·         Request (IRB, Inves/gator, other etc.) 
·         DSMB recommenda/on 
Monitoring visits will be performed annually, at a minimum. The sponsor-
inves/gator will permit direct access to the study monitors and appropriate 
regulatory authori/es to the study data and to the corresponding source 
data and documents to verify the accuracy of these data. 
Primary responsibili/es of the monitors will include verifying the following: 
·         Inves/gator qualiﬁca/ons 
·         Facili/es and equipment 
·         Storage, dispensing and disposi/on of inves/ga/onal products 
·         Protocol compliance 
·         Informed consent 
·         Training and delega/on of authority 
·         Subject eligibility 
·         Recruitment, screening and enrollment 
Page 
 of 
 
Template  Revised On: 11/01/2021
34
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
·         Veriﬁca/on of data and data clariﬁca/on 
·         Adverse event repor/ng 
·         FDA correspondence 
·         Devia/ons 
18.2. Data Safety Monitoring  
Adverse Event (AE) vs. Serious Adverse Event (SAE): An adverse event is any undesirable 
experience associated with the use of a medical product in a par>cipant. A serious 
adverse event (SAE) should immediately be reported to the FDA when the par>cipant 
outcome is: 
 
•
Death: Report if you suspect that the death was an outcome of the adverse 
event, and include the date if known.  
•
Life-threatening: Report if suspected that the pa>ent was at substan>al risk of 
dying at the >me of the adverse event, or use or con>nued use of the device or 
other medical product might have resulted in the death of the pa>ent. 
•
Hospitaliza9on (ini9al or prolonged): Report if admission to the hospital or 
prolonga>on of hospitaliza>on was a result of the adverse event. Emergency 
room visits that do not result in admission to the hospital should be evaluated for 
one of the other serious outcomes (e.g., life-threatening; required interven>on 
to prevent permanent impairment or damage; other serious medically important 
event). 
•
Disability or Permanent Damage: Report if the adverse event resulted in a 
substan>al disrup>on of a person's ability to conduct normal life func>ons, i.e., 
the adverse event resulted in a signiﬁcant, persistent or permanent change, 
impairment, damage or disrup>on in the pa>ent's body func>on/structure, 
physical ac>vi>es and/or quality of life. 
•
Congenital Anomaly/Birth Defect: Report if you suspect that exposure to a 
medical product prior to concep>on or during pregnancy may have resulted in an 
adverse outcome in the child. 
•
Required Interven9on to Prevent Permanent Impairment or Damage (Devices): 
Report if you believe that medical or surgical interven>on was necessary to 
preclude permanent impairment of a body func>on, or prevent permanent 
damage to a body structure, either situa>on suspected to be due to the use of a 
medical product. 
•
Other Serious (Important Medical Events): Report when the event does not ﬁt 
the other outcomes, but the event may jeopardize the pa>ent and may require 
medical or surgical interven>on (treatment) to prevent one of the other 
outcomes. Examples include allergic bronchospasm (a serious problem with 
Page 
 of 
 
Template  Revised On: 11/01/2021
35
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
breathing) requiring treatment in an emergency room, serious blood dyscrasias 
(blood disorders) or seizures/convulsions that do not result in hospitaliza>on. 
The development of drug dependence or drug abuse would also be examples of 
important medical events. 
 Severity of an adverse event: The following guidelines will be used to describe severity 
of an adverse event.  
 
•
Mild: Events require minimal or no treatment and do not interfere with the 
par>cipant’s daily ac>vi>es.  
•
Moderate: Events result in a low level of inconvenience or concern with the 
therapeu>c measures. Moderate events may cause some interference with 
func>oning. 
•
Severe: Events interrupt a par>cipant’s usual daily ac>vity and may require 
systemic drug therapy or other treatment. Severe events are usually poten>ally 
life-threatening or incapacita>ng.  Of note, the term “severe” does not 
necessarily equate to “serious”. 
Rela9onship to study interven9on: The following guidelines will be used to describe the 
“relatedness” of an adverse event.  
 
•
Deﬁnitely Related: There is clear evidence to suggest a causal rela>onship, and 
other possible contribu>ng factors can be ruled out. The clinical event, including 
an abnormal laboratory test result, occurs in a plausible >me rela>onship to 
study interven>on administra>on and cannot be explained by concurrent disease 
or other drugs or chemicals. The response to withdrawal of the study 
interven>on (dechallenge) should be clinically plausible. The event must be 
pharmacologically or phenomenologically deﬁni>ve, with use of a sa>sfactory 
rechallenge procedure if necessary. 
•
Probably Related: There is evidence to suggest a causal rela>onship, and the 
inﬂuence of other factors is unlikely. The clinical event, including an abnormal 
laboratory test result, occurs within a reasonable >me aner administra>on of the 
study interven>on, is unlikely to be a=ributed to concurrent disease or other 
drugs or chemicals, and follows a clinically reasonable response on withdrawal 
(dechallenge). Rechallenge informa>on is not required to fulﬁll this deﬁni>on. 
•
Poten9ally Related: There is some evidence to suggest a causal rela>onship (e.g., 
the event occurred within a reasonable >me aner administra>on of the trial 
medica>on). However, other factors may have contributed to the event (e.g., the 
par>cipant’s clinical condi>on, other concomitant events). Although an AE may 
rate as “poten>ally related” soon aner discovery, it can be ﬂagged as requiring 
Page 
 of 
 
Template  Revised On: 11/01/2021
36
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
more informa>on and later be upgraded to “probably related” or “deﬁnitely 
related”, as appropriate. 
•
Unlikely to be related: A clinical event, including an abnormal laboratory test 
result, whose temporal rela>onship to study interven>on administra>on makes a 
causal rela>onship improbable (e.g., the event did not occur within a reasonable 
>me aner administra>on of the study interven>on) and in which other drugs or 
chemicals or underlying disease provides plausible explana>ons (e.g., the 
par>cipant’s clinical condi>on, other concomitant treatments). 
•
Not Related: The AE is completely independent of study interven>on 
administra>on, and/or evidence exists that the event is deﬁnitely related to 
another e>ology. There must be an alterna>ve, deﬁni>ve e>ology documented 
by the clinician. 
Expectedness: The Inves>gator will be responsible for determining whether an adverse 
event is expected or unexpected. An adverse event will be considered unexpected if the 
nature, severity, or frequency of the event is not consistent with the risk informa>on 
previously described for the study interven>on. 
Repor9ng of adverse events: Informa>on on all adverse events will be collected 
including the: 
 
•
Event descrip>on 
•
Time of onset 
•
Assessment of severity 
•
Rela>onship to study interven>on 
•
expectedness 
•
Time of resolu>on/stabiliza>on of the event  
All adverse events occurring while on study will be documented appropriately regardless 
of rela>onship. All adverse events will be followed to adequate resolu>on. 
Any medical condi>on that is present at the >me that the par>cipant is screened will be 
considered as baseline and not reported as an adverse event. However, if the 
par>cipant’s condi>on deteriorates at any >me during the study, it will be recorded as an 
adverse event.  
The inves>gator will record all reportable events with start dates occurring any >me 
aner informed consent is obtained un>l 7 (for non-serious adverse events) or 30 days 
(for serious adverse events) aner the last day of study par>cipa>on.  At each study visit, 
Page 
 of 
 
Template  Revised On: 11/01/2021
37
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
the inves>gator will inquire about the occurrence of the adverse event since the last 
visit.  
The following are considered “Promptly Reportable Events” by the UMN IRB and will 
be reported as “Reportable New Informa9on” within 5 business days of learning of the 
event: 
 
•
Unexpected Death: Unexpected death of a locally enrolled par>cipant/subject 
who has not withdrawn from the research whether the death is considered 
related to the research or not. Death is considered unexpected if the risk of 
death is not listed in the consent form or is not listed as a possible event in 
protocol-related documents such as the IRB approved protocol or the 
Inves>gator’s Brochure.  
•
Risk: Informa>on that indicates a new or increased risk, or a safety issue. 
•
New informa>on (e.g., an interim analysis, safety monitoring report, publica>on 
in the literature, sponsor summary report, or inves>gator ﬁnding) indicates an 
increase in the frequency or magnitude of a previously known risk, or uncovers a 
new risk. Do not submit Inves>ga>onal New Drug (IND) safety le=ers, Medwatch 
reports, or other such individual reports to the IRB unless, in the opinion of the 
inves>gator, the event or informa>on in the report cons>tutes a UPIRTSO or the 
report requires a change to the protocol and/or the consent form. 
•
An adverse event that indicates a poten>al increase in risk or reduc>on in beneﬁt 
(such as those that may prompt a change to the protocol or consent form). 
•
An inves>gator brochure, package insert, or device labeling is revised to indicate 
an increase in the frequency or magnitude of a previously known risk, or to 
describe a new risk.  
•
Withdrawal, restric>on, or modiﬁca>on of a marketed approval of a drug, device, 
or biologic used in a research protocol. 
•
Protocol viola>on that harmed subjects or others or that indicates par>cipants/
subjects or others might be at increased risk of harm. 
•
Complaint of a par>cipant/subject that indicates par>cipants/subjects or others 
might be at increased risk of harm or at risk of a new harm.  
•
Any changes signiﬁcantly aﬀec>ng the conduct of the research outside of the 
inves>gator’s control or not directed by the inves>gator, e.g., a new therapy for 
the condi>on under study is proving highly eﬀec>ve.  
•
Harm: Any harm experienced by a par>cipant/subject or other individual that, in 
the opinion of the inves>gator, is unexpected and at least probably related to the 
research procedures. 
Page 
 of 
 
Template  Revised On: 11/01/2021
38
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
•
A harm is “unexpected” when its speciﬁcity or severity is inconsistent with risk 
informa>on previously reviewed and approved by the IRB in terms of nature, 
severity, frequency, and characteris>cs of the study popula>on. 
•
A harm is “probably related” to the research procedures if, in the opinion of the 
inves>gator, the research procedures more likely than not caused the harm. 
•
Non-compliance: Allega>on of inves>gator or study team noncompliance or 
ﬁnding of inves>gator or study team noncompliance. 
•
Audit: Audit, inspec>on, or inquiry by a federal agency (e.g. FDA Form 483).  
•
Report: Data safety monitoring reports from councils, commi=ees, or boards 
charged with data and safety oversight ac>vi>es; or other reports such as FDA 
non-approval le=ers.  
•
Researcher error: Failure to follow the protocol due to the ac>on or inac>on of 
the inves>gator or research staﬀ.  
•
Conﬁden>ality: Unauthorized disclosure of conﬁden>al informa>on.  
•
Protocol Devia>on: Change to the protocol taken without prior IRB review to 
eliminate an apparent immediate hazard to a subject.  
•
Incarcera>on: Incarcera>on of a subject in a study not approved by the IRB to 
involve prisoners.  
•
Complaint: Unresolved subject complaint. 
•
Suspension: Suspension or premature termina>on by the sponsor, inves>gator, 
ins>tu>on or other IRB.  
•
Unan>cipated adverse device eﬀect: Any serious adverse eﬀect on health or 
safety or any life-threatening problem or death caused by, or associated with, a 
device, if that eﬀect, problem, or death was not previously iden>ﬁed in nature, 
severity, or degree of incidence in the inves>ga>onal plan or applica>on 
(including a supplementary plan or applica>on), or any other unan>cipated 
serious problem associated with a device that relates to the rights, safety, or 
welfare of subjects.  
•
Disqualiﬁca>on / Termina>on: Change in qualiﬁca>on of any member of the 
study team based on state medical board, hospital medical staﬀ ac>on, or other 
disqualiﬁca>on by professional board or employ. 
•
Informa>on that is not listed above does not require repor>ng to the University 
of Minnesota IRB.  
19.
Provisions to Protect the Privacy Interests of Par9cipants 
19.1. Protec>ng Privacy:  
Conﬁden/ality of the research par/cipants will be maintained. All data will be 
stored in locked oﬃces and will not be released without consent of par/cipants. 
Data to be used in scien/ﬁc presenta/ons or publica/ons will not contain 
par/cipant iden/ﬁers. 
Page 
 of 
 
Template  Revised On: 11/01/2021
39
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
All material will be used exclusively for research. Data obtained will be stored in a 
conﬁden/al database without direct iden/ﬁers. The principal inves/gator and 
designated study staﬀ will have access to the linkages, which will be stored in a 
separate, secured loca/on. Hard copies of data, including source documents with 
iden/ﬁers, will be kept in locked ﬁle cabinets in a locked oﬃce un/l the 
comple/on and publica/on of the study, at which /me any iden/ﬁers will be 
removed and data will be stored at a secure storage facility for 6 years. Access to 
the locked ﬁle cabinet will be given to the study coordinators and principal 
inves/gator only. Any study ﬁles that will be shared with the University of 
Minnesota will remove pa/ent iden/fying informa/on. 
19.2. Access to Par>cipants:  
Participants will be fully informed of the ways in which their data will/may be used 
during the informed consent process. The research team has been trained in conducting 
these conversations and the participants are also assessed for their understanding of 
consent prior to initiating any study procedures 
20.
Compensa9on for Research-Related Injury 
20.1. Compensa>on for Research-Related Injury:  In the event that research-
related ac/vi/es result in an injury, treatment will be provided to the 
par/cipant (e.g., ﬁrst aid, emergency treatment, and follow-up care as 
needed). Care for such injuries will be billed in the ordinary manner to the 
par/cipant or the par/cipant’s insurance company. 
20.2. Contract Language: N/A 
21.
Consent Process 
21.1. Consent Process (when consent will be obtained):  
During the in-person screening visit: Once deemed eligible through an in-person 
screening and the par/cipant wishes to be enrolled in the study, a member of the 
research team will provide a paper copy of the consent form and read it to the 
individual and answer any ques/ons the individual has. Both the par/cipant and 
research team member will sign the consent form to cer/fy it and a paper copy 
will be provided to the par/cipant. At this /me, the HIPAA Authoriza/on form will 
also be signed by the par/cipant. Signed paper copies of both the informed 
consent and HIPPA authoriza/on will then be given to the par/cipant and will be 
scanned and stored in Advarra EDC or UMN Secure Box, whichever is 
recommended by the IRB.   
Page 
 of 
 
Template  Revised On: 11/01/2021
40
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
If the par/cipant is screened through a phone mee/ng or via virtual visit on Zoom 
and deemed eligible, the consen/ng process will occur at the ini/al research visit 
using the procedures described above.Upon coming in for the ﬁrst baseline 
assessment visit, the consent form will then be signed along with the HIPAA form. 
Signed paper copies will be provided to the par/cipant and scanned and stored in 
Advarra EDC or UMN Secure Box, whichever is recommended by the IRB. 
During the consen/ng process, the member of the research team will ask 
ques/ons of the par/cipant to ensure understanding of the study and consent 
form and will encourage the par/cipant to ask ques/ons.  
21.2. Waiver or Altera>on of Consent Process (when consent will not be 
obtained): N/A 
21.3. Waiver of Wri=en/Signed Documenta>on of Consent (when wri=en/signed 
consent will not be obtained): 
We are reques/ng a waiver of wri+en/signed documenta/on of consent for 
the screening por/on of this study. A short phone script will be read to the 
par/cipant before any screening ques/ons are asked. The par/cipant will 
need to provide verbal consent to answering these screening ques/ons 
before proceeding. 
21.4. Non-English Speaking Par>cipants:  N/A 
21.5. Par>cipants Who Are Not Yet Adults (infants, children, teenagers under 18 
years of age): N/A 
21.6. Cogni>vely Impaired Adults, or adults with ﬂuctua>ng or diminished 
capacity to consent: N/A 
21.7. Adults Unable to Consent: N/A 
●
Permission:  
●
Assent: 
Page 
 of 
 
Template  Revised On: 11/01/2021
41
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
●
Dissent: 
22.
Sebng 
22.1. Research Sites:  
All data collec/on will take place on the University of Minnesota Duluth campus 
in the Neural Func/on and Recovery Lab (107 Chester Park Building).   
22.2. Interna>onal Research: N/A 
23.
Mul9-Site Research N/A 
23.1. Study-Wide Number of Par>cipants:  
23.2. Study-Wide Recruitment Methods:  
23.3. Study-Wide Recruitment Materials:  
23.4. Communica>on Among Sites: 
23.5. Communica>on to Sites:  
24.
Coordina9ng Center Research N/A 
24.1. Role:  
24.2. Responsibili>es:  
24.3. Oversight:  
24.4. Collec>on and Management of Data:  
25.
Resources Available 
25.1. Resources Available:  
PI will complete 90 minute PI Primer training. The PI has graduate student 
support and will be wri/ng a grant for a part-/me research coordinator for this 
project. The PI also has acquired a 3 credit release for 2022-2023 AY to dedicate 
Page 
 of 
 
Template  Revised On: 11/01/2021
42
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
to this project. The PI is expected to dedicate 5 hours per week to this project, 
with some weeks requiring more/less depending upon enrollment. The PI 
an/cipates 10-12 hours per week for a part /me research coordinator. Services 
from Clinical Transla/onal Research Services (CTRS) have been and will con/nue 
to be used in the planning, execu/on and monitoring of the study as needed. In 
addi/on, BDAC will also con/nue to be used as a resource for assistance in the 
sta/s/cal analysis of the data. 
26.
References 
Antal, A., Alekseichuk, I., Bikson, M., Brockmöller, J., Brunoni, A. R., Chen, R., Cohen, L. 
G., Dowthwaite, G., Ellrich, J., Flöel, A., Fregni, F., George, M. S., Hamilton, R., 
Haueisen, J., Herrmann, C. S., Hummel, F. C., Lefaucheur, J. P., Liebetanz, D., Loo, 
C. K., … Paulus, W. (2017). Low intensity transcranial electric s>mula>on: Safety, 
ethical, legal regulatory and applica>on guidelines. Clinical Neurophysiology, 
128(9), 1774–1809. h=ps://doi.org/10.1016/j.clinph.2017.06.001 
Ferree, T. C., Luu, P., Russell, G. S., & Tucker, D. M. (2001). Scalp electrode impedance, 
infec>on risk, and EEG data quality. Clinical Neurophysiology, 112(3), 536–544. 
h=ps://doi.org/10.1016/S1388-2457(00)00533-2 
Ferrucci, R., Cortese, F., & Priori, A. (2015). Cerebellar tDCS: How to Do It. The 
Cerebellum, 14(1), 27–30. h=ps://doi.org/10.1007/s12311-014-0599-7 
Grimaldi, G., Argyropoulos, G. P., Bas>an, A., Cortes, M., Davis, N. J., Edwards, D. J., 
Ferrucci, R., Fregni, F., Galea, J. M., Hamada, M., Manto, M., Miall, R. C., Morales-
Quezada, L., Pope, P. A., Priori, A., Rothwell, J., Tomlinson, S. P., & Celnik, P. 
(2016). Cerebellar Transcranial Direct Current S>mula>on (ctDCS): A Novel 
Approach to Understanding Cerebellar Func>on in Health and Disease. The 
Neuroscien/st, 22(1), 83–97. h=ps://doi.org/10.1177/1073858414559409 
Page 
 of 
 
Template  Revised On: 11/01/2021
43
44

MEDICAL PROTOCOL (HRP-590)
PROTOCOL TITLE: Combining cerebellar tDCS and constraint-induced language therapy in non-
ﬂuent aphasia: a novel approach to target discourse 
VERSION DATE:  08/09/2023
Hilari, K., Byng, S., Lamping, D. L., & Smith, S. C. (2003). Stroke and Aphasia Quality of 
Life Scale-39 (SAQOL-39): Evalua>on of Acceptability, Reliability, and Validity. 
Stroke, 34(8), 1944–1950. h=ps://doi.org/10.1161/01.STR.0000081987.46660.ED 
Matsumoto, H., & Ugawa, Y. (2017). Adverse events of tDCS and tACS: A review. Clinical 
Neurophysiology Prac/ce, 2, 19–25. h=ps://doi.org/10.1016/j.cnp.2016.12.003 
Richardson, J. D., & Dalton, S. G. (2016). Main concepts for three diﬀerent discourse 
tasks in a large non-clinical sample. Aphasiology, 30(1), 45–73. h=ps://doi.org/
10.1080/02687038.2015.1057891 
Williams, L. S., Weinberger, M., Harris, L. E., Clark, D. O., & Biller, J. (1999). Development 
of a Stroke-Speciﬁc Quality of Life Scale. Stroke, 30(7), 1362–1369. h=ps://
doi.org/10.1161/01.STR.30.7.1362 
Page 
 of 
 
Template  Revised On: 11/01/2021
44
44