it typically improves in the weeks and months after stroke , yet about 50% of patients are left with long - term residual deficits .
few studies have documented the possibility of treatment - induced improvements in post - stroke language functions after 12 months .
traditionally , aphasia interventions utilize compensatory communication strategies to assist the participant in immediate communication needs .
multi - modal strategies include gesturing , writing , drawing , and augmentative low- and high - technology systems , with a common expectation that use of the alternative communication techniques will decrease naturally as the language capabilities increase .
these interventions improve overall communication abilities , but questions have been asked whether they contribute to the recovery of language function , or whether they actually contribute to a learned non - use phenomenon . to counteract the possibility of learned non - use , therapies utilizing restraint have been developed to mirror constraint - induced motor therapies . while it is relatively easy to restrain an unaffected extremity in motor therapies , restraining attempts to communicate non - verbally can be more difficult .
constraint - induced aphasia therapy ( ciat ) encourages intensive verbal practice with supported verbal cuing while excluding the use of previously habitual compensatory strategies . in ciat ,
the theoretical model of taub s motor system for use - dependent cortical re - organization has been applied to a language - based program . in this model
, it has been postulated that the behavior of attempting to speak without success leads to communication frustration .
this then results in fewer speaking attempts , more reliance on compensatory strategies , and less cortical stimulation in the language areas .
the ciat framework provides a structured supportive environment , with clinician guidance and shaping , positive reinforcement from group members , and social interaction opportunities .
the theory is that the supportive environment and speaking opportunities will encourage more verbal attempts and stimulate cortical reorganization .
thus , the goal of the present study was to provide evidence for the potential efficacy of ciat when compared to no - intervention in patients with chronic ( > 1 year ) post - stroke aphasia .
more specifically , this randomized , controlled , blinded pilot study was conducted in order to estimate effect sizes , allowing the design of an appropriately powered trial .
subjects were recruited into this institutional review board - approved study by word of mouth from among the stroke and aphasia clinics at the university of cincinnati and university of alabama at birmingham , and from local aphasia support groups .
we also listed the study on www.clinicaltrials.gov ( registered nct00843427 ; pi : szaflarski ) , and several contacts were received directly from patients . after providing consent for screening ,
the inclusion criteria were chronic aphasia related to a single ischemic stroke in the left middle cerebral artery ( lmca ) distribution ( i.e. , diagnosis of a single lmca stroke was confirmed by medical record review including admission notes for the incident stroke and the results of brain imaging obtained prior to enrollment ) , token test in an impaired range ( score 40 ) , and pre - stroke fluency in english .
the exclusion criteria were history of degenerative ( e.g. , dementia or parkinson s disease ) or metabolic disorder ( e.g. , encephalopathy ) or supervening illness ( e.g. , brain tumor or other cancer ) , history of severe depression or other mental illness , and positive pregnancy test in women of childbearing age .
five potential participants were excluded after interview . the format and the goals of the ciat program
all patients indicated their understanding of the goals of the program prior to signing the informed consent ; they also understood that they may be randomized to a no - intervention group , and that the follow - up testing will need to be performed .
of the 27 who were offered participation , 3 were excluded before randomization : 2 had a normal token test and 1 was hospitalized for reasons unrelated to the study .
fourteen subjects were randomized to receive ciat ( 34 participants per group ; 4 groups were assembled ) and 10 to receive no - intervention ( figure 1 ) .
demographic and clinical data of the participants are provided in table 1 . after obtaining the informed consent , we initially screened the patients for the presence of aphasia with token test ( tt ) and categorized the severity of aphasia as mild ( tt=40 - 37 ) , moderate ( tt=36 - 17 ) or severe ( tt=16 - 0 ) .
responders were defined as patients with at least a 20% relative improvement in at least 2 of the 5 primary scores in the 2-week period .
retainers were those patients whose 12-week score was not less than the 2-week score on at least 2 of the 5 outcome measures .
the 2-week ciat protocol was a closely monitored , individualized program embedded within a larger group activity . to ensure consistency of the intervention
training ( approximately 46 hours ) was conducted by alb prior to initiating any intervention session including basic theory of learned non - use , and the procedures for the treatment .
clinicians also viewed sample videos that exemplified the nature and set - up of the ciat intervention , and they were taught a hierarchy of cues that ranged from most to least supportive ( e.g. , imitation to verbal reminder ) . during the first day of intervention , clinicians had no information on participants abilities as , by design , they did not participate in the initial evaluations .
the measures were administered by coordinators who were blinded to group assignment ( figure 1 ) . to enhance the chance for successful implementation of cues during the ciat sessions , clinicians maintained a cuing tracking form that described the interaction between another clinician and their participant partners .
the types of cues provided were tracked with a binary notation of whether the cuing resulted in a successful communication .
this technique of behaviorally monitoring another clinician rather than self - monitoring was established in our previous study .
clinicians and participants were rotated during each day s session in order to provide a balance in communication partners . at the end of day 1 , alb studied the cuing tracking forms and the videos to create an individual treatment plan for the next day s session .
the treatment plan included identifying individual baseline linguistic strengths , suggested hierarchy of most beneficial cues , behaviors to constrain , and specific linguistic targets or goals .
the treatment plan was reviewed with the clinicians before the second day of therapy . from the second day
onwards , clinicians promoted individualized support with cues at a linguistic level suitable for each person and continued data tracking .
each day , clinicians reviewed the individual program and levels and made adjustments as needed . at the beginning of each session day , the clinicians reminded each participant of the goals and constraints that had been established for them .
for example , a participant who was strong in producing nouns , but limited in verbs , had a goal to add a verb to create a 2-word phrase .
if a participant demonstrated a milder aphasia , then the d - level hierarchy of sentences was implemented .
the treatment program for each of the 34 participant groups lasted 2 weeks , with direct therapy for about 4 hours per day for 10 consecutive weekdays .
the sessions were organized into 4 45-minute periods , with a 1015 minute break in between each session . socialization between clients and clinicians
was encouraged throughout the program , even during the break periods . at the beginning of each session , participants were dealt cards and they were instructed to play a go - fish type game . the cards provided the opportunity for the participants to interact with each other during an ongoing game that engaged participants visual , attention , and memory skills , although these were not specifically targeted .
the cards provided visual stimuli of line drawings of nouns ( singular , plural to elicit numbers , and with colors ) and photos of action verbs .
clinicians were encouraged to use redirecting phrases such as  try again  and  are you sure ?  rather than using negative responses . if the other participants responded positively and the communicative exchange was successful , clinicians were instructed not to correct ; communicative success is more important than the sentence accuracy .
whenever clinicians were observed to manage cards for the participant , this was discouraged ; clinicians were trained to be supportive while encouraging independence .
consistent with the current standards of care , the no - intervention group did not receive any specific treatment and the participants were asked to continue all previous activities as usual .
all participants were asked not to take part in any other intervention during their involvement in the study and all complied .
patients were randomized by the study statistician ( cjl ) after the patients received all pre - requisite activities ( consenting , clinical record review , neuropsychological aphasia testing ( nat ) ) .
patients were assigned to receive either 2 weeks of ciat , or no - intervention , and then to undergo nat within one week and 3 months of ciat completion ( figure 2  consort diagram ) .
we used a simple scheme that randomized each block of patients to either ciat or control .
randomization occurred after consent , and with the statistician blinded to participant performance on screening and baseline testing .
we did not replace subjects who do not complete the full 2 weeks of therapy .
after randomization , sealed study charts containing all pre - intervention testing results ( nat ) were funneled through the study biostatistician ( cjl ) to the therapists .
therapists set up the intervention groups so that the coordinators ( cb , anm ) who collected all nat data throughout the study remained blinded to group assignment .
participants were asked not to reveal their group assignment to coordinators during the post - treatment interactions .
all participants received nat which included : ( 1 ) the boston naming test ( bnt ) , ( 2 ) the controlled oral word association test , ( 3 ) the semantic fluency test ( sft ) , ( 4 ) the complex ideation subtest from the boston diagnostic aphasia examination ( bdae ) , ( 5 ) the peabody picture vocabulary test iii ( ppvt iii ) , and ( 6 ) the mini - communicative activities log ( mini - cal ) which is a subjective measure of communicative abilities .
the study coordinators , who were extensively trained in the use of these measures and blinded to group assignment , administered the nat measures within 1 week prior to ciat and again during both the first week the twelfth week following ciat completion .
all data were entered into redcap ( research electronic data capture ) for subsequent analysis .
one patient did not complete the 12 week visit or testing , and 7 additional patients were missing at least 1 nat score .
the primary analysis used independent samples t - tests to examine the differences in nat scores at each time point between the intervention and control groups , and effect sizes and 95% confidence intervals were calculated .
the secondary analysis was an ad hoc analysis comparing the characteristics of patients who demonstrated a response or change in nat scores to patients who did not .
independent t - tests , the mann - whitney u test , and fisher s exact test were used to compare patient characteristics between patients who demonstrated a response or change and patients who did not .
all statistical analyses were conducted using spss 22.0 ( ibm corporation , armonk , ny ) and r 2.15.3 ( base package ) .
subjects were recruited into this institutional review board - approved study by word of mouth from among the stroke and aphasia clinics at the university of cincinnati and university of alabama at birmingham , and from local aphasia support groups .
we also listed the study on www.clinicaltrials.gov ( registered nct00843427 ; pi : szaflarski ) , and several contacts were received directly from patients . after providing consent for screening ,
the inclusion criteria were chronic aphasia related to a single ischemic stroke in the left middle cerebral artery ( lmca ) distribution ( i.e. , diagnosis of a single lmca stroke was confirmed by medical record review including admission notes for the incident stroke and the results of brain imaging obtained prior to enrollment ) , token test in an impaired range ( score 40 ) , and pre - stroke fluency in english .
the exclusion criteria were history of degenerative ( e.g. , dementia or parkinson s disease ) or metabolic disorder ( e.g. , encephalopathy ) or supervening illness ( e.g. , brain tumor or other cancer ) , history of severe depression or other mental illness , and positive pregnancy test in women of childbearing age .
five potential participants were excluded after interview . the format and the goals of the ciat program
all patients indicated their understanding of the goals of the program prior to signing the informed consent ; they also understood that they may be randomized to a no - intervention group , and that the follow - up testing will need to be performed .
of the 27 who were offered participation , 3 were excluded before randomization : 2 had a normal token test and 1 was hospitalized for reasons unrelated to the study .
fourteen subjects were randomized to receive ciat ( 34 participants per group ; 4 groups were assembled ) and 10 to receive no - intervention ( figure 1 ) .
after obtaining the informed consent , we initially screened the patients for the presence of aphasia with token test ( tt ) and categorized the severity of aphasia as mild ( tt=40 - 37 ) , moderate ( tt=36 - 17 ) or severe ( tt=16 - 0 ) .
responders were defined as patients with at least a 20% relative improvement in at least 2 of the 5 primary scores in the 2-week period .
retainers were those patients whose 12-week score was not less than the 2-week score on at least 2 of the 5 outcome measures .
the 2-week ciat protocol was a closely monitored , individualized program embedded within a larger group activity . to ensure consistency of the intervention , all clinicians completed a training program .
training ( approximately 46 hours ) was conducted by alb prior to initiating any intervention session including basic theory of learned non - use , and the procedures for the treatment .
clinicians also viewed sample videos that exemplified the nature and set - up of the ciat intervention , and they were taught a hierarchy of cues that ranged from most to least supportive ( e.g. , imitation to verbal reminder ) . during the first day of intervention , clinicians had no information on participants abilities as , by design , they did not participate in the initial evaluations .
the measures were administered by coordinators who were blinded to group assignment ( figure 1 ) . to enhance the chance for successful implementation of cues during the ciat sessions , clinicians maintained a cuing tracking form that described the interaction between another clinician and their participant partners .
the types of cues provided were tracked with a binary notation of whether the cuing resulted in a successful communication .
this technique of behaviorally monitoring another clinician rather than self - monitoring was established in our previous study .
clinicians and participants were rotated during each day s session in order to provide a balance in communication partners . at the end of day 1 , alb studied the cuing tracking forms and the videos to create an individual treatment plan for the next day s session .
the treatment plan included identifying individual baseline linguistic strengths , suggested hierarchy of most beneficial cues , behaviors to constrain , and specific linguistic targets or goals .
the treatment plan was reviewed with the clinicians before the second day of therapy . from the second day
onwards , clinicians promoted individualized support with cues at a linguistic level suitable for each person and continued data tracking .
the tracking provided constant reminders to only provide cues that resulted in successful communication . each day
, clinicians reviewed the individual program and levels and made adjustments as needed . at the beginning of each session day , the clinicians reminded each participant of the goals and constraints that had been established for them .
for example , a participant who was strong in producing nouns , but limited in verbs , had a goal to add a verb to create a 2-word phrase .
if a participant demonstrated a milder aphasia , then the d - level hierarchy of sentences was implemented .
the treatment program for each of the 34 participant groups lasted 2 weeks , with direct therapy for about 4 hours per day for 10 consecutive weekdays .
the sessions were organized into 4 45-minute periods , with a 1015 minute break in between each session .
socialization between clients and clinicians was encouraged throughout the program , even during the break periods . at the beginning of each session , participants were dealt cards and they were instructed to play a go - fish type game . the cards provided the opportunity for the participants to interact with each other during an ongoing game that engaged participants visual , attention , and memory skills , although these were not specifically targeted .
the cards provided visual stimuli of line drawings of nouns ( singular , plural to elicit numbers , and with colors ) and photos of action verbs .
clinicians were encouraged to use redirecting phrases such as  try again  and  are you sure ?  rather than using negative responses . if the other participants responded positively and the communicative exchange was successful , clinicians were instructed not to correct ; communicative success is more important than the sentence accuracy . whenever clinicians were observed to manage cards for the participant , this
consistent with the current standards of care , the no - intervention group did not receive any specific treatment and the participants were asked to continue all previous activities as usual .
all participants were asked not to take part in any other intervention during their involvement in the study and all complied .
patients were randomized by the study statistician ( cjl ) after the patients received all pre - requisite activities ( consenting , clinical record review , neuropsychological aphasia testing ( nat ) ) .
patients were assigned to receive either 2 weeks of ciat , or no - intervention , and then to undergo nat within one week and 3 months of ciat completion ( figure 2  consort diagram ) .
we used a simple scheme that randomized each block of patients to either ciat or control .
randomization occurred after consent , and with the statistician blinded to participant performance on screening and baseline testing .
we did not replace subjects who do not complete the full 2 weeks of therapy .
after randomization , sealed study charts containing all pre - intervention testing results ( nat ) were funneled through the study biostatistician ( cjl ) to the therapists .
therapists set up the intervention groups so that the coordinators ( cb , anm ) who collected all nat data throughout the study remained blinded to group assignment .
participants were asked not to reveal their group assignment to coordinators during the post - treatment interactions .
all participants received nat which included : ( 1 ) the boston naming test ( bnt ) , ( 2 ) the controlled oral word association test , ( 3 ) the semantic fluency test ( sft ) , ( 4 ) the complex ideation subtest from the boston diagnostic aphasia examination ( bdae ) , ( 5 ) the peabody picture vocabulary test iii ( ppvt iii ) , and ( 6 ) the mini - communicative activities log ( mini - cal ) which is a subjective measure of communicative abilities .
the study coordinators , who were extensively trained in the use of these measures and blinded to group assignment , administered the nat measures within 1 week prior to ciat and again during both the first week the twelfth week following ciat completion .
all data were entered into redcap ( research electronic data capture ) for subsequent analysis .
one patient did not complete the 12 week visit or testing , and 7 additional patients were missing at least 1 nat score .
missing scores were left missing , and are excluded from analysis . the primary analysis used independent samples t - tests to examine the differences in nat scores at each time point between the intervention and control groups , and effect sizes and 95% confidence intervals
the secondary analysis was an ad hoc analysis comparing the characteristics of patients who demonstrated a response or change in nat scores to patients who did not .
independent t - tests , the mann - whitney u test , and fisher s exact test were used to compare patient characteristics between patients who demonstrated a response or change and patients who did not .
all statistical analyses were conducted using spss 22.0 ( ibm corporation , armonk , ny ) and r 2.15.3 ( base package ) .
there were 24 patients enrolled in the study , 14 in the intervention group , and 10 in the control group ( see consort diagram ) .
two patients in the intervention group did not complete the study , 1 due to lack of transportation and 1 due to hospitalization with an illness unrelated to the study .
overall , there were no significant differences in demographic characteristics and past medical history between the 2 groups ( table 1 ) .
the mean age was 57 ( sd11 ) years in the intervention group and 51 ( sd13 ) years in the control group .
most patients were caucasian , 10/14 ( 71% ) in the intervention group and 9/10 ( 90% ) in the control group .
there were few statistically significant differences in nat scores between the intervention and control groups ( table 2 ) .
specifically , differences were observed in subjective communication abilities assessed with the mini - cal .
patients who received ciat scored higher on the mini - cal at 12 weeks after intervention compared to the control group ( mean 31 vs. 23 ; difference=8 , 95% ci 1.3 to 13.5 , p=0.019 ) .
the sft was marginally higher 2 weeks after intervention in ciat patients than controls ( mean 21 vs. 12 ; difference 9 , 95% ci 0.3 to 17.8 , p=0.058 ) .
overall , 5/24 ( 21% ) of participants could be classified as a  responders  , as defined in the methods section .
responders were less likely to have a history of hypertension 0/5 ( 0% ) , compared to non - responders 10/14 ( 53% ) , p=0.053 .
of the 5 patients who demonstrated a change in nat scores during the course of the study , only 1 ( 20% ) retained the change at the twelve - week visit .
there were 24 patients enrolled in the study , 14 in the intervention group , and 10 in the control group ( see consort diagram ) .
two patients in the intervention group did not complete the study , 1 due to lack of transportation and 1 due to hospitalization with an illness unrelated to the study .
overall , there were no significant differences in demographic characteristics and past medical history between the 2 groups ( table 1 ) .
the mean age was 57 ( sd11 ) years in the intervention group and 51 ( sd13 ) years in the control group .
most patients were caucasian , 10/14 ( 71% ) in the intervention group and 9/10 ( 90% ) in the control group .
there were few statistically significant differences in nat scores between the intervention and control groups ( table 2 ) .
specifically , differences were observed in subjective communication abilities assessed with the mini - cal .
patients who received ciat scored higher on the mini - cal at 12 weeks after intervention compared to the control group ( mean 31 vs. 23 ; difference=8 , 95% ci 1.3 to 13.5 , p=0.019 ) .
the sft was marginally higher 2 weeks after intervention in ciat patients than controls ( mean 21 vs. 12 ; difference 9 , 95% ci 0.3 to 17.8 , p=0.058 ) .
responders were less likely to have a history of hypertension 0/5 ( 0% ) , compared to non - responders 10/14 ( 53% ) , p=0.053 .
of the 5 patients who demonstrated a change in nat scores during the course of the study , only 1 ( 20% ) retained the change at the twelve - week visit .
in this prospective , preliminary , randomized , blinded study of patients with chronic post - stroke aphasia , we estimated the effect of ciat on linguistic performance . while the results are largely not statistically significant , a few points need to be discussed .
first , the study included patients with highly variable levels of post - stroke aphasia , making the comparisons between the groups somewhat difficult .
second , the observed effects are consistent with improvement in the ciat group beyond that in the control group , with trends towards statistical significance for some of the variables even in this small sample . defining a responder as a participant with 20% improvement on at least 2 of the 5 tests , then the number needed to show significant between - group differences would be 62 and allows for the design of a more comprehensive trial .
finally , a significant improvement was noted in the mini - cal results for the ciat group compared to controls .
this indicates that , at least subjectively , the patients in ciat group perceived more improvement over time than participants in the control group . reasons for the participants perception of improvement , as measured by the mini - cal , may be related to the social activity of the therapy sessions . in order to isolate the variable of social interaction from ciat theory
, future studies should consider including a study arm involving exposure to social interaction with the same duration and frequency as the ciat group , but without the ciat intervention .
social factors may be related to both clinicians and other participants in the group . to date , few reports on the potential efficacy of ciat have been published .
five studies in patients with chronic aphasia have included both a treatment group and a control group [ 8,2225 ] . only in the original study
were participants randomized to treatment group ; however , unlike the current study , the personnel collecting linguistic data were not blinded to treatment assignment in any of these studies . in the original study ,
in the other 4 studies ciat was compared to other treatment approaches  either model - based aphasia therapy ( training based on functional deficit ) , ciat plus written module , pace , or model - oriented aphasia therapy ( moat ) .
in addition to the above studies , a recent study compared modified ciat to conventional aphasia therapy in patients with less than 4 months ( subacute ) since the incident ischemic or hemorrhagic stroke .
all these studies showed that while participants receiving treatment improved linguistic performance , between - group differences were minimal , if any .
thus , when comparing the results of the original study by pulvermuller et al . and the results of the subsequent studies , including ours , the questions of training intensity and social interactions between participants , and participants and clinicians need to be considered ; both can contribute to improved communicative abilities via increased verbal communication practice .
we did not show any statistically significant improvement in objective tests of linguistic performance from before to after treatment .
one of the reasons for this lack of statistical significance in our small sample size is the high variability in language scores observed in both groups ( figure 3 ) .
a future study enrolling a highly - variable group of participants would require a sample size of only 62 per treatment group to show a significant advantage of ciat over passive observation .
but , the effects observed by us are in line with the results of the original study by pulvermuller et al .
we identified important considerations for study design that will minimize unnecessary variability and maximize the potential for observing treatment benefit .
treatment fidelity needs to be monitored , either via independent reviewers performing video or by direct review of the conducted sessions .
a transfer package similar to that offered in motor rehabilitation studies will need to be developed and applied to this group .
also , the outcome measures should include measures of pre- and post - intervention discourse and assess changes in the severity of aphasia using , e.g. , the western aphasia battery - revised ; assessing linguistic complexity using mean length of utterances ; or indices of syntactic form .
in addition to the above , stratification by severity , education , and socioeconomic status might emphasize the magnitude of improvement relative to the degree of aphasia .
finally , other factors , including the effects of lesion size and location on changes in aphasia diagnosis ( type ) during the therapy session , should be assessed .
modest improvements were noted in the ciat group on the collected objective tests that were not noted in the control group , forming the basis for estimating effect sizes needed for a comprehensive study .
moreover , the ciat group reported significant subjective improvement that confirms the importance of this approach .
larger randomized controlled trials that adopt the measures suggested to reduce variability and maximize observable benefit are warranted .
 backgroundfew studies have documented the possibility of treatment - induced improvements in language functions 12 months or longer after stroke . 
 the purpose of the current study was to provide a preliminary estimate of efficacy of constraint - induced aphasia therapy ( ciat ) when compared to no - intervention in patients with chronic ( > 1 year ) post - stroke aphasia in order to provide the data needed to design an appropriately powered trial.material/methodsthis was a randomized , controlled , single - blinded , pilot trial . 
 we identified 32 patients with chronic post - stroke aphasia . 
 of these , 27 were offered participation , and 24 were randomized ( consort diagram ) : 14 to ciat and to 10 to no - intervention . 
 ciat groups received up to 4 hours / day of intervention for 10 consecutive business days ( 40 hours of therapy ) . 
 outcomes were assessed within 1 week of intervention and at 1 and 12 weeks after intervention and included several linguistic measures and a measure of overall subjective communication abilities ( mini - communicative abilities log ( mini - cal ) ) . to maintain blinding 
 , clinicians treating patients ( ciat group ) did not communicate with other team members and the testing team members were blinded to treatment group assignment.resultsoverall , the results of this pilot trial support the results of previous observational studies that ciat may lead to improvements in linguistic abilities . at 12 weeks , the treatment group reported better subjective communication abilities ( mini - cal ) than the no - intervention group ( p=0.019 ) . 
 other measures trended towards better performance in the ciat group.conclusionsin this randomized , controlled , and blinded pilot study , intensive language therapy ( ciat ) led to an improvement in subjective language abilities . 
 the effects demonstrated allow the design of a definitive trial of ciat in patients with a variety of post - stroke aphasia types . 
 in addition , our experiences have identified important considerations for designing subsequent trial(s ) of ciat or other interventions for post - stroke aphasia . 
Background
Material and Methods
Subjects
Definitions
Description of the intervention
Randomization
Blinding
Measures
Data analysis
Results
Subjects
Primary analysis
Secondary analysis
Discussion
Conclusions