Impact of Intensive Social Interaction on Post-Stroke Depression in Individuals With Aphasia
Phase: NA
Conditions: Post-stroke Depression, Post-stroke Aphasia
Sponsor: University Medicine Greifswald

 
 
 
Intensive Social Interaction for Treatment of Post-Stroke 
Depression in Subacute Aphasia: The CONNECT Trial 
 
Study Protocol 
 
 
 
Benjamin Stahl, PhD1, 2, 3 *; Saskia Millrose, MSc4, 5 *; Petra Denzler, MSc5; 
Guglielmo Lucchese, MD, PhD2; Frank Jacobi, PhD6; Agnes Flöel, MD2, 7 
1 Faculty of Science, Medical School Berlin, Germany 
2 Department of Neurology, University Medicine Greifswald, Germany 
3 Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany 
4 Department of Psychology, Freie Universität Berlin, Germany 
5 Median-Klinik Berlin-Kladow, Germany 
6 Psychologische Hochschule Berlin, Germany 
7 German Centre for Neurodegenerative Diseases, Rostock and Greifswald, Germany 
* Authors contributed equally. 
 
 
 
 
 
 
 
Correspondence: 
Prof. Dr. Benjamin Stahl 
Medical School Berlin 
Naturwissenschaftliche Fakultät 
Rüdesheimer Straße 50 
14197 Berlin, Germany 
E-mail: benjamin.stahl@medicalschool-berlin.de 
 
Clinical Trial Registration: 
www.clinicaltrials.gov; identifier: NCT04318951. 
 
Last Update: 
March 2019 
 

The CONNECT Trial: Study Protocol and Statistical Analysis Plan 
 
 
 
2 
Methods 
Study design and setting 
Following the CONSORT guidelines, we here present a parallel-group, blinded-
assessment, quasi-randomised controlled phase-IIB triala in an outpatient rehabilitation centre in 
Berlin, Germany, between 2020 and 2022 (study acronym: CONNECT). This trial was 
approved by the ethics review board at University Medicine Greifswald, Germany (file number: 
BB 033/17). A team of neuropsychologists will obtain written informed consent from all 
participants, with ample time for questions and reflection to account for aphasia-immanent 
comprehension problems. 
Study sample and power analysis 
After routine referral to the study team, we will invite potential participants to a screening 
session to check their eligibility. Inclusion criteria will be: left-hemispheric cortical or 
subcortical ischemic or haemorrhagic event; subacute phase (0.5–6 months after the 
cerebrovascular lesion); German as first native language; right-handedness according to the 
Edinburgh Handedness Inventory;29 diagnosis of PSD, as defined by international classification 
code F06.32;5 diagnosis of aphasia, as confirmed by the Bielefeld Aphasia Screening, with no 
more than two standard deviations below the average score on the subscale “Auditory 
Comprehension” to ensure understanding of basic instructions.30 Exclusion criteria will be: 
other psychopathological or neurological conditions; premorbid history of recurrent depressive 
disorder; severe uncorrected vision or hearing that may prevent intensive social interaction 
during therapy or testing; serious non-verbal cognitive deficits, as revealed by the Corsi Block-
Tapping Task.31 
A target sample of 60 individuals will participate in the present phase-IIB trial. This sample 
size was calculated in an a-priori power analysis (α = 0.05; 1–β = 0.80; Cohen’s f = 0.390; 
numerator degrees of freedom: 1; number of groups: 2; number of covariates: 2; resulting 
n = 54; expected dropout rate = 10%; final n = 60).32 Our effect size estimate derives from 
published phase-IIA RCT data on Beck’s Depression Inventory (BDI), as specified 
below (converted from η2 = 0.132).20 Notably, an extended goal of the current phase-IIB trial 
will be to deliver a more precise effect size estimate for a subsequent phase-III RCT. We 
assumed a more conservative dropout rate for ILAT than seen in previous work.19, 23 
                                                 
a Study on aspects of feasibility and potential efficacy as an intermediate step to a phase-III RCT. 

The CONNECT Trial: Study Protocol and Statistical Analysis Plan 
 
 
 
 
 
3 
Quasi-randomisation and blinding 
Eligible candidates will be assigned to one of two treatment arms (each n = 30). Our ILAT 
protocol requires three individuals with aphasia to be present simultaneously in a rehabilitation 
centre for daily sessions over a 1-month treatment period. During the recruitment phase, 
occasionally fewer than three eligible candidates per treatment period will stay at the 
rehabilitation centre. To meet this logistical challenge in our phase-IIB trial—with a focus on 
treatment feasibility in PSD—candidates will receive ILAT only if enough fellow players are 
available to form groups of three individuals. Otherwise, candidates will receive the control 
intervention. The quasi-randomisation procedure will be administered by a person who does not 
participate in any stage of therapy or testing. A neuropsychologist with expertise in aphasia will 
perform all diagnostic sessions. This person will be blinded to group assignment and will not 
have patient contact aside from the testing. Data will be unmasked for final evaluation purposes 
by the study team who will not attend any of the therapy or testing sessions. 
Treatment and procedures 
ILAT requires individuals with aphasia to engage in everyday request and planning 
communication.18 Groups of three individuals and a therapist are seated around a table and 
provided with picture cards showing different objects (e.g., bottle) or action 
scenes (e.g., drinking). Barriers on the table prevent players from seeing each other’s cards. 
Each card has a duplicate that belonged to one of the other players. The goal is to obtain this 
duplicate from a fellow player by requesting the depicted object (e.g., “Give me the […]”) or by 
proposing an action based on the visualised scene (e.g., “Let’s […] together”). The rich turn-
taking structure of ILAT serves as a vehicle for intensive use of formulaic expressions: (i) If the 
duplicate is available, the players compare the depicted objects or scenes; in the case of a match, 
the addressee hands over the corresponding card to the person who initiated the request or 
action-planning sequence (e.g., “Here you are”—“Thank you”—“You’re welcome”). (ii) If the 
duplicate is not available, the addressee rejects the request or proposed action (e.g., “I’m 
sorry”—“No problem”—“Too bad”). (iii) In the event of misunderstandings, the players ask 
clarifying questions (e.g., “Pardon me?”). 
We will recreate training materials and procedures described previously.23 The therapist 
will continuously apply positive reinforcement via encouraging feedback to diminish the 
likelihood of cognitive-affective distress caused by lack of social stimulation, in line with a 
common model of depression aetiology.1 Practical experience with ILAT demonstrates that 
players often imitate the therapists’ behaviour by starting to support one another verbally, thus 

The CONNECT Trial: Study Protocol and Statistical Analysis Plan 
 
 
 
 
 
4 
multiplying the amount of positive reinforcement exchanged during treatment (e.g., “Well 
done!”). Self-cueing strategies will be allowed, along with gestures to accompany—but not 
replace—spoken language. ILAT involves five weekly sessions, each with a duration of one 
hour, over a total treatment period of one calendar month. We do not set a minimum amount of 
treatment in our protocol to compensate for missed sessions, since dropout rates for ILAT have 
been extremely low in prior work.19, 23 The treatment will be delivered by a team of speech-
language therapists and neuropsychologists who will receive training and continuous 
supervision before and during the trial. 
Standard care will conform to state-of-the-art procedures of rehabilitation centres certified 
in Germany. Depending on the participants’ diagnoses and needs, standard care will include: 
antidepressant medication (drug and dosage defined individually by a physician blinded to 
group randomisation and study purpose; substance classes: selective serotonin reuptake 
inhibitors, tri- and tetracyclics), occupational therapy (2–3 hours weekly), physiotherapy (2–
3 hours weekly), and non-intensive speech-language therapy (2–3 hours weekly with emphasis 
on phonology, lexicon and syntax, as detailed in a large-scale RCT protocol33). 
Outcomes and testing 
Feasibility, our primary outcome, will considered to be met if at least two-thirds of 
participants in Group I complete all ILAT sessions offered during the 1-month treatment period. 
As a co-primary outcome of potential efficacy, we will administer a 20-item version of the 
BDI.34 This self-report measure is known for its excellent psychometric properties, including 
construct validity and test-retest reliability, in individuals without aphasia. The BDI has been 
successfully piloted in individuals with aphasia, as indicated by phase-IIA RCT data.20 To 
complement the BDI, we will use a clinician-rated measure with good psychometric properties 
as an additional co-primary outcome, a 7-item version of the Hamilton Rating Scale for 
Depression.35 
Reflecting the potential influence of treatment-induced or spontaneous progress in verbal 
expression on change in depression severity, we will employ the combined Aachen Aphasia 
Test (AAT) subscales “Repetition” and “Naming” as a secondary outcome and covariate in our 
analyses.36 These two AAT subscales proved to be most sensitive to ILAT-mediated gains in 
chronic aphasia, as shown by RCT data.19, 23 Moreover, participants will complete the Self-
Efficacy Questionnaire, a self-report measure conceived to quantify personal confidence in 
overcoming obstacles when accomplishing difficult tasks.37 Low scores on this secondary 

The CONNECT Trial: Study Protocol and Statistical Analysis Plan 
 
 
 
 
 
5 
outcome constitute a risk factor for cognitive-affective distress, suggesting a significant negative 
relationship between results on the Self-Efficacy Questionnaire and BDI.38 The Self-Efficacy 
Questionnaire will provide an external criterion to determine the psychometric adequacy of our 
self-report co-primary outcome, the BDI, in individuals with aphasia, given the possibility of 
serious deficits in understanding spoken instructions not ruled out during eligibility screening, 
as specified above. 
A neuropsychologist blinded to group allocation will conduct all diagnostic sessions. The 
neuropsychologist will have substantial experience in communication with individuals suffering 
from aphasia-immanent comprehension problems. Testing will take place immediately 
before (baseline: T1; BDI, HAM-D, and AAT) and within 24 hours after the 1-month treatment 
period (endpoint: T2; BDI, HAM-D, AAT, and Self-Efficacy Questionnaire). 
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