Developing Effective Response Inhibition Training for Symptom Relief in Obsessive-Compulsive and Related Disorders and Trichotillomania
Phase: NA
Conditions: Obsessive Compulsive Disorder, Trichotillomania
Sponsor: University of Wisconsin, Milwaukee

Developing Effective Response Inhibition Training for Symptom Relief in OCD and Trichotillomania 
 
NCT02059980 
7/1/2018 
 
STUDY PROTOCOL 
Effective behavioral and pharmacological treatments exist for obsessive-compulsive disorder (OCD), but a 
significant portion of patients with OCD refuse to receive, drop out of, or otherwise fail to respond to the 
currently most efficacious treatments.1,2 Suboptimal clinical outcomes and under-utilization of these treatments 
often result from practical barriers such as adverse effects (e.g., intense distress during the exposure 
procedure or side effects of medication), high costs, and a lack of trained therapists.3 Despite the 
demonstrated efficacy of existing treatments, almost half of individuals with OCD continue to suffer from this 
extremely debilitating condition without adequate treatment. Thus, disseminable and cost-efficient therapeutic 
approaches with minimal adverse effects are required for OCD. In this regard, a promising therapeutic 
approach is computerized cognitive retraining which has recently shown success in improving psychiatric 
conditions by directly modifying biased or deficient cognitive processes that are considered to be central to 
such conditions.4-6 There is compelling evidence that poor response inhibition (RI) is a core cognitive feature of 
OCD7,8 and is its putative endophenotype.9 RI is the basic cognitive ability required to inhibit potent but 
inappropriate responses,10 and research indicates that RI can be functionally changed by practice.11 Despite 
the growing evidence for the significance of poor RI in OCD, it is unknown whether OCD symptoms can be 
improved using cognitive retraining designed to enhance the individual’s RI capabilities. To improve overall 
treatment response rates in OCD, it is vital to develop an effective intervention with minimal adverse effects 
that may result in enhanced treatment acceptability, patient retention, and dissemination. 
Our long-term goal is to understand how to change anomalous cognitive processes underlying OCD 
and its related conditions such as trichotillomania (TTM) in order to develop and disseminate effective 
computer-based cognitive interventions. The objective of the current R21 application is to examine the 
feasibility of using a computerized RI training (RIT) program to improve OCD-related symptoms. Our central 
hypothesis is that cognitive training designed to enhance RI will improve this problematic cognitive process in 
OCD and TTM and produce a significant reduction in OCD/TTM symptoms. This hypothesis is based on (a) 
existing behavioral, electrophysiological, and neuroimaging data suggesting poor RI as a core feature of OCD 
and TTM and (b) our preliminary data suggesting that RIT can be a useful therapeutic intervention for OCD 
and its related conditions characterized by poor RI. The expected results will lay a strong groundwork for future 
studies at the R01 level aimed at developing, testing and disseminating evidence-based RI-focused cognitive 
training for OCD that can be used as an adjunctive intervention to enhance existing treatments or as a stand-
alone intervention. We propose two specific aims and an exploratory aim for this proposal.  
Aim 1. To determine the effectiveness of computerized RIT in enhancing RI among OCD/TTM patients. 
We hypothesize that OCD/TTM patients who undergo the 8-session RIT program will show greater RI 
capabilities, relative to OCD/TTM patients who receive placebo cognitive training. 
Aim 2. To determine the utility of computerized RIT in improving OCD/TTM symptoms. We hypothesize 
that OCD/TTM patients who undergo the 8-session RIT program will show a greater reduction in OCD/TTM 
symptoms, relative to OCD/TTM patients who receive placebo cognitive training. 
Exploratory Aim. To evaluate the subjective treatment experiences and patient retention. To assess the 
end-user acceptability of the proposed cognitive training program, we will assess treatment acceptability and 
satisfaction as well as treatment refusal and drop-out rates. 
 

This project is innovative because it uses the approach of a novel cognitive training intervention to directly 
modify underlying cognitive abilities and improve OCD symptoms. The proposed RIT program has been 
designed as an engaging and immersive computer game to target a core cognitive deficit of OCD-related 
conditions, which is also in line with the NIH’s growing interest in computer game-based neuropsychiatric 
intervention. This project is expected to have a positive impact by generating important knowledge that will 
guide the development of an effective cognitive training program for OCD-related conditions that would 
potentially result in an effective, cost-efficient, and portable intervention with low adverse effects, or enhance 
the clinical outcomes of existing treatments as an adjunctive intervention. If successful, this line of translational 
research is expected to contribute to improving overall treatment response rates among individuals suffering 
from this debilitating and costly illness, yielding significant public health impact. 
 
 
APPROACH   
      Project Overview. Over the course of 2 years, 30 individuals with 
OCD/TTM will complete either RI Training (RIT; n=15) or Placebo 
Training (PLT; n=15). At baseline, participants will complete (a) 
clinician-administered rating and self-report scales for OCD/TTM 
symptoms, (b) questionnaires for other emotional symptoms, and (c) 3 
RI assessment tasks. Participants will then undergo 8-session cognitive 
training (RIT or PLT) over a 4-week period. Both participants and the 
independent evaluator (IE) will be blinded to the training condition. 
Potential adverse events will be assessed weekly during the 
intervention period by the IE. At post-training, we will re-evaluate 
participants’ symptom severity and RI performance. Treatment 
acceptability and satisfaction will also be measured at this point. At 1-
month follow-up, participants will be assessed again for the severity of 
OCD/TTM and other emotional symptoms and RI performance (see 
Figure 1). Regarding the overall timeline of the project, active 
recruitment will occur in Month 2 through 22 after the initial preparatory 
work (Month 1). Data analyses and preparation of manuscripts, 
conference presentations, and a grant application will occur in Month 
20 through 24.  
 
RESEARCH DESIGN 
      Participants.  We will recruit 30 individuals who meet the following inclusion criteria: (a) age between 18 
and 60, (b) a primary diagnosis of OCD/TTM as determined by the Structured Clinical Interview for DSM-5 
(SCID-5), (c) moderate level of OCD or TTM symptoms,47 and (d) IQ > 80 (on the Wechsler Abbreviated Scale 
of Intelligence-II). Exclusion criteria include: (a) current substance abuse/dependence, (b) current or past 
psychotic disorder, bipolar disorder, or schizophrenia, (c) presence of ADHD, or TS (conditions known for poor 
RI), (d) severe depressive symptoms (evidence suggests that executive function deficits in OCD are 
attributable to comorbid depression48,49), (e) current psychotherapy, (f) current psychoactive medications (a 
variety of pharmacological agents were shown to be implicated in RI, including dopamine, norepinephrine, and 
serotonin50-52), and (g) current suicidality.  
 
Cognitive Training Programs.  RIT is a 30-level computer game (with a story of defending a village from 
aliens), designed to offer systematic practice of RI focused primarily on action withholding and cancellation, 
incorporating parameters of go/no-go and stop-signal tasks. Main task materials are simple geometric figures 
(e.g, squares, circles). However, RIT is different from a mere repetition of existing go/no-go or stop-signal tasks 
in several important ways: (a) with ascending levels, RIT becomes more difficult by systematically varying RI 

task parameters integrated into each game level (i.e., frequencies of no-go or stop trials, stop-signal latencies, 
and increased stimulus potency via set switching); (b) RIT guides participants to make individually-tailored 
progress toward their own levels of challenge (i.e., each level is repeated until high accuracy is reached); (c) 
RIT contains video-game features to maximize participant’s motivation (e.g., engaging story and graphics, and 
display of record scores); and (d) RIT provides trial-by-trial performance feedback to help participants make 
conscious efforts to improve their ongoing performance. In each 45-min session, five 7-min game levels are 
offered with brief inter-level breaks. After completing each level, a result page will summarize the participant’s 
performance. The central training components of RIT are the same as those used in our pilot studies. 
Similar to other cognitive retraining paradigms, the RIT is based on the rationale that repeated practice of 
the core cognitive process central to the condition would result in clinically meaningful improvement. The RIT is 
expected to allow individuals to practice (a) suppressing pre-potent stimulus-response association, (b) 
inhibiting potent ongoing response, (c) selectively inhibiting response to inappropriate stimuli, (d) exerting 
cognitive flexibility to changing targets, and (e) maintaining goal-directed responses in the given context.  
Based on the evidence suggesting RI as a core feature of OCD and our preliminary data, we predict that RIT 
will generate meaningful clinical improvement in OCD beyond a simple task practice effect which would 
improve only RI task performance without affecting OCD symptoms.  
Similarly, PLT is a 30-level computer game but presents only go trials, and thus provides no opportunity to 
practice RI components (i.e., action withholding and cancellation).  However, its 30-level structure and task 
stimuli are identical to those of the RIT program, and they also become increasingly difficult across level (by 
more abrupt onsets and increasingly shorter duration of the stimuli). We expect PLT to have negligible effects 
on RI capabilities and OCD symptoms. The RIT/PLT will be administered in a small therapy room at the UWM 
Psychology Clinic and Anxiety Lab. The participant will complete each training session following the 
computerized instructions. A trained administrator will be present in all sessions to assist in the event of any 
technical difficulties. 
 
Primary and Other Outcome Measures 
Considering the inclusion of two diagnostic conditions (OCD and TTM), we will obtain clinician-rated 
symptom ratings for both conditions, using the Yale-Brown Obsessive-Compulsive Scale and the NIMH TTM 
Symptom Severity Rating Scale. The primary outcome index will be a z-transformed score of the symptom 
ratings obtained from the two rating scales. We will also use the Clinical Global Impression (CGI) rating scale 
is a widely used brief assessment tool for evaluating illness severity, global improvement or change, and 
therapeutic response. 
We will also use the stop-signal and go/no-go task, in which participants should promptly indicate the 
direction (left vs. right) of an arrow on each trial, but inhibit response when an auditory stop signal is presented. 
Stop Signal Reaction Time (SSRT; time taken to complete the inhibitory process) is estimated using the 
tracking algorithm, which adjusts the stop signal delay automatically (by 50ms) to maintain the rate of 
successful inhibition on stop-signal trials at 50%.10 This particular version has successfully demonstrated the 
RI deficits in both OCD patients and unaffected first-degree relatives.7,43 The SSRT is a behavioral RI outcome 
measure for this study. The go/no-go task asks participants to quickly press a button for letters (e.g., Q, P, T; 
go trials) except to the letter X (no-go trial).67-69 Twenty-five percent of the task constitutes no-go trials. The RI 
index from this task is the number of commission errors. Patients with OCD showed abnormal activity in fronto-
striatal circuits while performing this type of go/no-go task.35,69   
 
 
STATISICAL ANALYSIS PLAN 
Power Analysis.  We conducted power analyses using a conventional large effect size (f = .40). With α 
= .05, a correlation of .5 among repeated measures, and a nonsphericity correction of .6, the required sample 
size is 9 per group to achieve the power of .80 in detecting a large group X time interaction effect (f=.40). 
Based on the recommendation from Ukoumunne et al.70 that allows standard power analyses to be used for 

multilevel models by multiplying the sample size by the design effect, the necessary sample size is 20 after an 
adjustment by a factor of 1.1, which was derived from an assumed intraclass correlation of .05. Taking into 
account 25% patient attrition (n=5), a total of 25 would offer an adequate sample size to detect a medium to 
large effect size. Thus, this proposal (N=30) is sufficiently powered (=.90) to detect a large effect, but is 
underpowered (=.50) to detect a medium effect (f=.25).  
Specific Aim 1 - To determine the effectiveness of RIT in enhancing RI among OCD/TTM patients. To 
attain the objective of Aim 1, we will test the working hypothesis that RIT will show greater improvement in RI 
performance than PLT. Our primary analytic strategy is multilevel modeling, which effectively handles multi-
session data with hierarchical structure (i.e., three time points nested in individuals), missing data, and serial 
correlation. To test the hypothesis, the level-1 intercept will be regressed on training condition to examine 
group differences, and the slope for time will be regressed on training condition to produce a cross-level 
interaction to examine the differential rate of change in RI performance between the two groups. 
Specific Aim 2 - To determine the utility of the RIT in reducing OCD/TTM symptoms. To attain this 
objective, we will test the working hypothesis that RIT will show a greater reduction in OCD/TTM symptoms 
than PLT. Our primary analytic strategy is random effects mixed model analyses, in which the level-1 intercept 
will be regressed on training condition to examine group differences and the slope for time will be regressed on 
training condition to produce a cross-level interaction that examines group differences in the rate of change in 
OCD/TTM symptom z-scores.