Cognitive Rehabilitation and Exposure Therapy for Veterans With Hoarding Disorder
Phase: NA
Conditions: Hoarding Disorder
Sponsor: VA Office of Research and Development

Cognitive Rehabilitation and Exposure Therapy for 
Veterans with Hoarding Disorder 
 
NCT02402647 
 
February 1, 2023 

Current Proposal 
Proposed Study Design 
The proposed study includes a 26-session controlled, randomized clinical trial designed to test the 
hypothesis that while targeting avoidance produces changes in HD symptoms, targeting executive dysfunction 
as well as avoidance will lead to even greater symptomatic changes, and secondarily in functioning and quality 
of life. Further, we will explore outcome moderators (age and baseline executive functioning) and time to 
maximum effect. To do this, we will compare CREST (CCT + ET) to ET alone. The study will be comprised of 4 
phases (see Figure 2) (1) Pre-Treatment Evaluation Phase (1 assessment); (2) During Treatment Evaluation 
Phase (3 assessments; at sessions 7, 13, and 21); (3) End of Treatment (1 assessment after session 26); and 
4) 3 and 6-month Follow-up Phase (2 assessments).
Patient Inclusion/Exclusion
The inclusion criteria are designed to enroll a sample of Veteran HD patients with some level of 
executive functioning impairment in order to engage treatment targets. We do not believe this will exclude a 
significant number of Veterans. In our most recent sample of 55 HD patients over age 60, 73% were impaired 
on one or more of four DKEFS subtests (Tower, Trail Making, Verbal Fluency, or Color-Word Interference 
Tests). For the proposed study, patients must demonstrate impaired performance on one or more of the five 
DKEFS subtests given (Color-Word Interference, Verbal Fluency, Trail Making, Design Fluency, Tower Test). 
These criteria are optimal in that it will allow for a range of executive functioning within our sample to look at 
predictors of response as well as allow us to engage this intermediary target.  
Further, in order to ensure that we 
have an enriched ED sample, we will include 
individuals between the ages of 45-85. This 
older sample will allow for increase efficiency 
in finding Veteran participants with a level of 
ED, given that we know older adults with HD 
show ED22,31, and that HD symptoms (which 
are correlated with ED) may become worse 
with age45. Given the mixed findings on ED 
in younger HD populations, this will prevent 
us from having a floor effect, thus ensuring 
that we have a sample where we can 
engage targets. Further, with this age range 
we will be able to examine how aging 
contributes to treatment outcomes, a gap in 
the existing research. 
Other inclusion criteria include (1) 
Veterans age 45-85; (2) Hoarding Disorder 
diagnosis outlined by the Diagnostic and 
Statistical Manual of Mental Disorders, Fifth 
Edition (DSM-5)6 as measured by the 
Structured Interview for Hoarding Disorder 
(SIHD)67; (3) HD as a primary diagnosis; (4) 
executive dysfunction as defined by an 
impaired scaled score (i.e., <7) on any of the following tests; DKEFS Color-Word Interference, Verbal Fluency, 
Trail Making, Design Fluency, Tower Test (5) stable on medications for at least 12 weeks, with no 
pharmacologic changes expected or made during the 12-month study (6) voluntary consent to participate. 
Exclusion criteria includes (1) diagnosis of a psychotic disorder, bipolar I, bipolar II disorder, substance abuse 
disorder as measured by the Mini-International Neuropsychiatric Interview (M.I.N.I.)68 (3) current or history of any 
neurodegenerative disease; (4) active suicidal ideation; (5) concurrent participation in any form of 
psychotherapy, or prior ET, CBT for HD, or CREST for HD. 
Recruitment and Randomization 
Recruitment will take place in through the San Diego VA utilizing existing recruitment method for our 
HD studies including review of consults submitted to the VA San Diego Anxiety Disorders clinic, posted flyers 
in the hospital, VA clinician outreach, participation in the San Diego Hoarding Task Force (PI is a founding 

member), and electronic media advertisements. The PI on the proposed project is the Program Director of the 
VA San Diego Anxiety Disorders Clinic, where Veterans with known HD symptoms are referred.  
Our group has a successful history of recruiting HD patients. Since 2009, we have received over 270 
geriatric (over age 60) HD referrals and since 2011 we have received over 125 midlife (under age 60) HD 
referrals. We have received an increase in calls (7 calls per week) since July 2013 due to our established 
reputation within the VA Healthcare System and San Diego County. Interestingly, through task force 
participation and electronic advertisements, we have been able to reach Veterans who were previously not 
receiving services at the VA and were able to enroll them in our local VA healthcare system.  Our funded HD 
studies within the lab have been completed ahead of schedule due to availability of participants. Thus, we will 
be able to meet our enrollment goals with our existing recruitment system.  
Recruitment targets will be 11-12 patients per study wave (see timeline below) for a total of 136 
patients, half of whom will be randomly assigned to CREST. Participants will be administered the Hoarding 
Rating Scale (HRS)69 over the phone by the study coordinator. If they score above a 4 on any item on the 
HRS, they will be scheduled for an in-person baseline assessment in their home to establish eligibility. 
Following informed consent, an independent rater will complete a baseline assessment to determine 
eligibility. After review of the baseline scores, Drs. Ayers and Twamley (Co-I) will determine eligibility based on 
consensus. Dr. Golshan, the study statistician, will prepare the randomization table prior to recruitment of 
subjects. Subjects will be randomized 1:1 ratio to one of two conditions.  
 
Retention 
Our group currently has a markedly low attrition rate for HD studies. We have had 0% attrition across 2 
open trials15,33 and 8 in our current randomized controlled trial (3 for CREST; 5 for control). Participants will be 
compensated for their baseline, post-treatment and follow-up assessment points ($80 total; $20 per 
assessment) and a bonus of $20 for completing all assessments as an additional incentive to participate in 
treatment. We will optimize follow-up with regular patient contact in treatment, mailings to confirm whereabouts 
(e.g., birthday and holiday cards), and consent to contact at least one person likely to know subject 
whereabouts. 
 
Treatment Conditions 
Format and Course of Treatment Given the chronic and severe nature of HD, researchers have found that it 
requires a relatively lengthy course of treatment14 (24-26 individual sessions)57,70. Both the control and 
experimental condition utilizes a 60 minute session-by-session manualized treatment protocol and will take 6 
months to complete. Each participant will 
receive 26 sessions of individual treatment. In 
the experimental condition, patients will receive 
7 sessions of CCT and 19 sessions of ET 
(consisting of exposure to discarding and 
acquiring modules). In the control condition, 
patients will receive 26 sessions of ET. The 
patient and therapist have their own workbook 
copy for both conditions to follow along during 
each session (Appendix 1 for CREST and 
Appendix 2 for ET condition). For the 
conceptualization of CREST, refer to Figure 3. 
 
Experimental Condition: CREST 
Compensatory Cognitive Training (CCT) 
Modules (7 sessions). Compensatory 
Cognitive Training60,61,62 is a manualized, low-
tech, cognitive training intervention designed to 
target cognitive impairments common in people 
with psychiatric illness. The original CCT 
treatment manual has been distributed to over 
250 clinicians and has been used with 
schizophrenia, brain injury, mild cognitive 
impairment, multiple sclerosis, Parkinson’s 

disease, and substance use disorder patients. The CCT modules specifically selected for CREST map onto 
known areas of HD neurocognitive deficits or weakness and include training in prospective memory, 
prioritizing, problem solving, planning, and cognitive flexibility. Because habit learning is also highly resistant to 
forgetting71, we aimed to help Veteran participants form new habits in executive functioning to automate tasks 
and reduce the active cognitive effort usually demanded for effective performance. CCT does not use 
computers, and strategies taught do not “train to the test” or use any of the outcome measures during training. 
It is believed that using CCT will aide in the implementation of ET exercises. That is, CCT will provide patients 
with the necessary skills to fully comply with treatment (attendance and homework completion) and tools to 
prevent relapse.  
A full outline of CCT modules is seen in Table 1. Given that HD patients are often disorganized and 
cannot manage their day to day demands, patients will be taught how to use a calendar system and practice 
utilizing their new scheduling skills. Specific details about calendar use are reviewed (e.g., when to check it, 
when to have a planning session, when to record dates, what to record, where it is kept, etc.).  
Next, Veteran participants are taught how to start new behavioral routines by linking tasks (e.g., doing 
therapy homework after taking medications) and how to use a to-do list. Often HD clients are unrealistic about 
how many tasks they can accomplish in one day and the amount of time required for each item. To-do item 
creation, checking of the list, and scheduling to-dos are discussed and added to the calendar system.  
 
Problem solving skills are then taught as HD patients have difficulty finding solutions and taking action 
towards solving everyday problems. The 6-step approach; Define the problem, Brainstorm solutions to the 
problem, Evaluate each solution, Select a solution to try, Try the solution, and Evaluate the solution (DBESTE) 
is reviewed through the use of worksheets. Appropriate planning strategies are then reviewed in conjunction 
with their new problem solving skills (e.g., You selected to call an exterminator for your roach problem, what 
steps do you have to take to accomplish this task?). Further, learning how to shift set or change their behaviors 
 
 
 
Table 1. CREST Modules, Target Domains, and Manual Content 
CCT Module (Target Domain) 
Session/Homework Content 
Session 1. Introduction to CCT and psychoeducation 
about the link between brain functioning and HD  
Discussion of patient’s experienced consequences of HD, barriers to treatment 
adherence and possible solutions, and treatment goals and expectations 
Session 2. Calendar use (Prospective Memory) 
Discussion of current/past calendar system; goal setting of where to keep calendar 
and when to use it; practicing use of calendar with “real-world” type scenario; using 
linking tasks and automatic places to help with daily activities 
Session 3. Linking tasks, using a “to do” list (Prospective 
Memory) 
Review of calendar use and linking tasks; using “to-do” lists along with calendar; 
determination of to do categories and frequencies; short-term prospective memory 
strategies (e.g., “can’t miss reminders”) 
Session 4-5. Problem solving  
Brainstorming practice exercises (therapist- and patient- provided examples); 6-step 
problem solving method; practice evaluating solutions for feasibility 
Session 6. Thinking flexibly and planning (Cognitive 
Flexibility) 
Self-talk and self-monitoring, brainstorming steps to meet a goal; practicing setting 
time lines for long-term goals. 
Session 7. Home visit and organizational preparation 
(Cognitive Flexibility) 
Creating a plan for organizing home (i.e., where types of items should be stored); 
brain storm "to-do" list for organization; rules of organizing; home maintenance 
system (current and proposed rules) 
ET Module  
Session/Homework Content 
Session 8. Exposure preparation 
Discussion of expectations, decision making, habituation, and avoidance; rules of 
discarding; motivational interviewing about willingness to change; acquisition 
hierarchy; fear of discarding hierarchy 
Session 9. Introduction to exposure therapy 
Review of organizational plan, rules of organizing, maintenance system, and rules of 
discarding; introduction to Subjective Units of Distress (SUDS) Ratings; discarding 
exposure 
Sessions 10-22: Exposure to discarding & acquiring 
Evaluation of progress; discarding exposure; discussion of reasons for saving and 
strategies for making discarding choices; introduction to advanced exposure (e.g., 
discussion of rules, preparing for sorting for a longer time and use of outside help); 
review of treatment goals 
Sessions 23-24: Advanced exposure 
Longer exposure time (2-4 hours) with outside help; Evaluation of progress; 
discussion of reasons for saving and strategies for making discarding choices; review 
of treatment goals 
Sessions 25-26: Relapse prevention and maintenance 
Review of progress in therapy; discussion of everyday uses for cognitive strategies 
(e.g., calendar use, "to do" lists, problem solving); exposure review; planning for the 
future 
 

when a previously identified “solution” is not working is also reviewed with real life examples (e.g., How many 
times do you tell yourself you will clean out the garage each weekend without success before you try another 
strategy? You still have a mouse infestation after trying your homemade remedy – when do you try something 
else?). Finally, basic organizational skills (e.g., filing, categorization) and maintenance routines (e.g., trash 
removal, home cleaning) are reviewed and operationalized. Daily homework is emphasized and reviewed at 
the beginning of each session. 
 
Exposure to Discarding and Acquiring Modules (19 sessions in CREST condition; all 26 
sessions in ET control condition). Symptoms of acquiring and saving are themselves avoidance behaviors 
that are performed to avoid internal distress related to negative thoughts and emotions72. Avoidance serves to 
reduce distress related to the beliefs regarding the necessity and utility of possessions73,72. In the CREST 
condition, the second part and the majority of treatment is dedicated to ET for discarding and not acquiring 
while in the control condition, the entire treatment will consist of ET. The ET utilizes in-vivo exposure exercises, 
beginning in the therapist’s office, but eventually taking place during home visits as these home sessions assist 
with the generalization of their new skill sets22. Pure ET is different than exposures provided in CBT for HD in 
that ET is not combined with cognitive therapy, motivational interviewing or any of the other components of 
CBT for HD.   
In ET for HD, the clients develop a hierarchy list of spaces in that evoke progressively greater fear if 
they were faced with having to make a decision about discarding. These discarding scenarios or spaces may 
range from some that are relatively easy to others that are incredibly difficult. For HD clients, fear hierarchies 
typically start with a space that has low clutter volume or there is less of an urge to save a particular type of 
item in that environment. The patient and therapist collaborate on creating this list and selecting a mild to 
moderately difficult space where the client will start exposure exercises.  
Concrete rules are established for exposure activities, such as only two piles to place items in during 
exposure (keep and discard), only the client can make the decision about the item, only handle the item once, 
kept items must be put away immediately after the exposure, discarded items must go to the 
trash/recycle/donation area immediately after the exposure, and report distress ratings out loud to track 
progress. 
 Clients are asked to bring the items into the office from the identified space on their hierarchy and then 
to pick up each item one by one and make a choice about keeping and discarding. There is an agreed upon 
length of time that the patient must engage in exposure exercises and the rationale for ET is reviewed at the 
beginning of each session. During exposures, therapists remind patients of their self-identified treatment goals 
and concrete challenge questions (e.g., How does keeping this help you with your hoarding problem? Would 
you be able to live without this item? If you really need it again, could you get one?) are asked in an effort to 
encourage discarding. Clients progress through own hierarchy and move into different spaces or scenarios 
once the space is completed.  
Ideally, habituation occurs over time and context and patients learn that they can tolerate the distress 
from the exposure activity74. Even if their distress does not decrease during the exposure, clients learn 
experientially that they can tolerate the distress. When obsession-related stimuli are repeatedly triggered, their 
toleration of fear increases75. Throughout sessions, clients learn that they do not experience terrible 
consequences when experiencing states of high anxiety while discarding. The goal is to generalize lessons 
learned from repeated exposures that trigger the feared reason for discarding or not acquiring. 
A small percentage of clients have excessive acquiring behaviors. If it is determined excessive 
acquiring is a problem based on the initial assessment (SI-R, Acquiring Subscale; score >13), exposures to not 
acquiring are designed (e.g., go to Walmart with cash in hand and not purchase items, go to swap meet and 
not purchase items, watch home shopping network with credit card in hand and not purchase) and guided by a 
hierarchy. The clinician will work with the participant on these non-acquiring exposures and discarding 
exposures simultaneously.  
 
Control Group: Exposure to discarding and acquiring (26 sessions). We propose to use a robust control 
condition, ET, with the same frequency and amount of therapist contact as CREST. Twenty-six weekly, 
individual ET sessions (6 months) will be delivered. The control group will receive ET for all 26 sessions and no 
cognitive training. As in CREST, the ET sessions will be manualized and copies utilized during session by both 
the patient and therapist.  
 
While we considered using the currently available CBT for HD21 as our control condition, ET will allow 
examination of the specific role that exposure plays in decreasing HD symptoms. Thus, we are investigating 

the impact of a concentrated individual component of treatment, which we believe is the true mechanism of HD 
symptom change. Further, we may find subgroups that benefit from a specific condition, allowing for refinement 
of future treatment. 
 
Staff 
Two part-time PhD-level clinicians experienced in exposure-based treatments will be hired and trained 
in both CREST and ET. These clinicians will be at the postdoctoral level and license eligible. Study clinicians 
will rotate on taking new participants. Volunteer research assistants (VRAs) will be utilized as clinician 
extenders due to the necessity of at-home labor assistance required in cluttered homes. Our lab has a history 
of recruiting and maintaining VRAs for HD treatment studies and currently has 10 HD clinical VRAs that are 
approved by our local VA. For the proposed project, a total of 6 clinical VRAs will be trained (see below) along 
with the clinicians. The VRAs will attend home visits with the study therapists and assist with exposure 
activities. The VRAs are present during supervision and their work is audiotaped. Two part-time (15 hrs per 
week) independent raters will be hired to conduct in home assessments throughout the study. One part-time 
study coordinator/data manager will be hired for the project and assist with phone screening, data 
organization/entry, and recruitment.  
 
Training and Supervision 
 
Both the clinicians and VRAs will attend the initial training and weekly supervision. The amount of 
training and preparation proposed for this investigation is influenced by standard clinical practice within mental 
health care and consistent with many VA evidence based training roll-outs. The initial 2-day training workshop 
(8 hours per day) will be provided by Dr. Ayers and will include review of manuals and homework sheets, 
videotaped demonstration, and role-played/modeled delivery of CREST and ET. Dr. Ayers has conducted over 
10 HD treatment workshops to mental health clinicians. Weekly 90-minute face-to-face skills based group 
supervision will be provided by Dr. Ayers. Supportive coaching, modeling, role-play, review of session 
audiotapes, and feedback of fidelity ratings will be used in supervision. The type of training program we have 
designed that places an emphasis on supervision and fidelity is also consistent with training models used for 
roll out of evidence based practices in large healthcare programs (e.g., VA). Independent raters will receive an 
initial 2-day training on neuropsychological assessment and ongoing weekly supervision from Dr. Elizabeth 
Twamley (Co-I).  
 
Fidelity 
In an effort to avoid therapist effects, the therapists will deliver both treatment conditions. While we 
considered issues of contamination, the cognitive rehabilitation components vary from the exposure sessions 
thus it would not be intuitive or feasible to deliver rehabilitation modules during the exposure sessions. The ET 
sessions start with the rationale for exposure and quickly moving to exposure to discarding and not acquiring; 
leaving no room for teaching compensatory cognitive strategies.  
In the present protocol, we propose to promote and measure treatment fidelity in several ways. First, in 
addition to training outlined above, study therapists will receive weekly supervision from Dr. Ayers. Second, 
therapists will have a checklist to guide them during the conduct of sessions. Third, all sessions of both 
interventions will be videotaped, and a random sample of 20% of videos from each randomized group will be 
selected by study statistician, Dr. Golshan, and will be reviewed within a week and rated for treatment fidelity 
and discriminability by Dr. Ayers utilizing a standard checklist to document presence of all program elements 
(See Appendix 3 and 4). We will define therapist compliance as 90% adherence to the items on the weekly 
checklist. Specific plans have been developed for responding to sub-threshold adherence, ranging from extra 
training to statistically controlling for adherence to replacing therapists (in the extreme).   
 
With respect to our blind, independent raters, intra-class correlation coefficients (ICC) will used to 
determine inter-rater reliability of individual items and scale scores for appropriate measurements. We will 
establish a good inter-rater reliability (ICC=.85) prior to any data collection. Each rater's score will be compared 
to the "Gold Standard" rater. The raters are required to achieve an ICC of at least .85 for all rating scales. To 
protect against "rater drift" over the course of the study, all raters will undergo reassessment semiannually. 
New raters hired during the course of the study will go through the reliability training and testing described 
above before they rate subjects. 
 
Measures  

Demographic and Diagnostic assessment (at baseline only) will assess inclusion criteria, including 
diagnosis, co-morbidities and cognitive impairment (Table 2). Diagnosis of HD will be assessed using the 
Structured Interview for Hoarding Disorder (SIHD)67, a recently developed but well-validated clinician-
administered instrument for diagnosing HD based on the DSM-5 criteria. The SIHD has demonstrated strong 
inter-rater reliability, convergent validity, and discriminant validity. Potential comorbidities will be assessed with 
the Mini-International Neuropsychiatric Interview (M.I.N.I.)68, a brief diagnostic interview that uses decision-tree 
logic to assess different mental disorders. This interview has demonstrated excellent reliability and validity (it 
produces the same diagnoses as the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) or 
Composite International Diagnostic Interview (CIDI) in 85-95% of cases), and it can be administered much 
more rapidly than other diagnostic interviews (e.g., SCID-I). 
 
Hoarding symptom severity (primary outcome) will be measured using the Savings Inventory-
Revised (SI-R)56, a 23-item self-report measure used to assess common hoarding symptoms. Subtests include 
excessive clutter, compulsive acquisition, and difficulty discarding. The SI-R has demonstrated good internal 
consistency, divergent validity, concurrent validity, divergent validity, test-retest reliability in clinical samples 
with hoarding. The total score will be used for analyses. 
 
Functional Capacity (secondary outcome) will be assessed using two different measures. The 
UCSD Performance-Based Skills Assessment (UPSA)76 is an assessment of everyday functioning skills 
involved in household chores (e.g., writing a shopping list based on a provided recipe), communication (e.g., 
rescheduling a doctor’s appointment), finance (e.g., paying a utility bill), recreation planning (e.g., planning an 
outing to the beach or zoo), and transportation (e.g., reading comprehension of a bus schedule). The UPSA 
has demonstrated high inter-rater reliability (0.91) and convergent validity with other performance-based 
measures. The total UPSA summary score will be used for analyses.  The UCSD SORT Test (U-SORT)77 will 
be used to measure Veteran participants’ organizational skills as they relate to functional capacity. During the 
administration of the U-SORT, participants are instructed to sort 42 household objects (e.g., bent and unbent 
paper clips, used and unused condiment packets) from a hypothetical “junk drawer” into either “keep” or “trash” 
piles. Participants are given two minutes to complete the task and one point is awarded for each correctly 
sorted item, for a total of 42 points. The U-SORT has high internal consistency ( = .86) and adequate 
convergent validity. The total U-SORT score will be used in analyses.  
 
Self-reported functioning (secondary outcome) will be assessed with the Specific Levels of 
Functioning test (SLOF)78, a 43-item questionnaire regarding areas such as interpersonal relationships, 
participation in community activities, and work skills. The SLOF has demonstrated excellent reliability and 
internal consistency. Further, the World Health Organization Disability Assessment Schedule (WHODAS 2.0)79, 
a 36-item, six domain (Cognitive, Mobility, Self-Care, Getting Along, Household, Work, Participation) 
assessment instrument developed by World Health Organization (WHO) to provide a standardized method for 
measuring health and disability across cultures will also be utilized. The WHODAS demonstrated total internal 
consistency (0.96) as well as domain-specific reliability (0.79-0.98) and concurrent validity with similar disability 
measures. A summary score will be generated using the “complex” scoring method.  
 
Quality of Life (secondary outcome) will be assessed using the Quality of Life in Neurological 
Disorders (Neuro-QoL) Positive Affect and Well-Being Short form80. The Neuro-QoL Positive Affect and Well-
Being - Short Form is a 9-item self-report measure that assesses aspects that related to a sense of well-being, 
life satisfaction, purpose and learning. The total score will be used for analyses.  
 
Avoidance (intermediary target) will be measured by the Acceptance and Action Questionnaire 2 
(AAQ-2)81, a 10 item, self-report measure of experiential avoidance and immobility that has demonstrated 
strong reliability (0.78-0.88). There is a precedence of using the AAQ-2 for measuring avoidance as a mediator 
of HD82. A Behavioral Avoidance Test (BAT) will also be utilized for assessing avoidance to sorting and 
discarding possessions in HD patients. The BAT has been validated for measuring avoidance in clinical 
obsessive compulsive disorder (OCD) samples83, and will be adjusted for use in HD samples. Participants and 
assessors will select three kinds of personal objects that cause the Veteran participants distress to discard and 
agree on 3-7 steps that would go into sorting/discarding the object (deciding whether to keep it, throw it away, 
or give it away; deciding where to put the object if keeping it, where to throw it away if tossing it, and where to 
take it if giving it away, etc.). The assessor will observe the participant performing as many steps for each 

object as they feel comfortable doing and for each step the participant at least partially completes, they will 
give a rating of their Subjective Units of Distress (SUDS) from 0-10. For each of the three object tasks the 
clinician will give a rating of 0-2 of the avoidance they observe in the participant, where zero indicates no 
avoidance, one indicates partial avoidance or that the participant did not fulfill all of the steps of the task, and 
two indicates that there was complete avoidance of the entire task of discarding the object. This process will be 
repeated in three rooms of their home; ideally the kitchen, bedroom, and living room pending accessibility. To 
create a composite, score the SUDS and the Avoidance scores will each be divided by their respective 
standard deviations and then summed together.  
 
Executive Functioning (intermediary target) will be assessed using multiple measures. The Delis-
Kaplan Executive Function System (D-KEFS)65 was specifically designed to detect deficits in high-level 
cognitive functions, such as from mild brain damage to the frontal lobe84 and has demonstrated strong 
reliability and validity in various clinical populations. We will administer five tests from the D-KEFS that 
examine components of executive functioning, such as inhibition (the Color-Word Interference Test), cognitive 
flexibility or switching (Verbal Fluency, Trails Tests, Design Fluency) and Planning (Towers). The Penn 
Conditional Exclusion Test (PCET)85 will be used as a measure of executive functioning in which Veteran 
participants must perform a computerized sorting task with three shifting sorting principles. The PCET is similar 
to the Wisconsin Card Sorting Test86, a classic test of executive functioning, but it has four alternate test 
versions that can be administered with comparable validity and reliability, better allowing for repeated testing 
over time.  
 
 
Table 2. Assessments and Timeline 
Measure 
Baseline 
Session 
7 
Session 
13 
Session 
21 
Post 
Assessment 
(After 
Session 26) 
3-Month 
Follow-
up 
6-
Month 
Follow-
up 
Diagnostic Assessment 
Structured Interview for Hoarding Disorder (SIHD) 
X 
  
  
  
  
  
  
Mini-International Neuropsychiatric Exam (MINI) 
X 
  
  
  
  
  
  
Hoarding severity (Primary Outcome) 
Savings Inventory-Revised (SI-R) 
X 
X 
X 
X 
X 
X 
X 
Functional Capacity (Secondary Outcome) 
UCSD Performance-Based Skills Assessment 
(UPSA) 
X 
X 
X 
X 
X 
X 
X 
UCSD SORT Test (U-SORT) 
X 
X 
X 
X 
X 
X 
X 
Self-Reported Functioning (Secondary Outcome) 
Specific Levels of Functioning test (SLOF) 
X 
X 
X 
X 
X 
X 
X 
World Health Organization Disability Assessment 
Schedule (WHODAS 2.0) 
X 
X 
X 
X 
X 
X 
X 
Quality of Life (secondary outcome) 
Quality of Life in Neurological Disorders (Neuro-QoL) 
X 
X 
X 
X 
X 
X 
X 
Executive Functioning (Intermediary Target) 
Delis-Kaplan Executive Function System (D-KEFS) 
Color-Word Interference, Verbal Fluency, Trails 
Tests, Design Fluency, Towers 
X 
X 
  
  
X 
X 
X 
Penn Conditional Exclusion Test (PCET) 
X 
X 
  
  
X 
X 
X 
Avoidance (Intermediary Target) 
Behavioral Avoidance Test (BAT) 
X 
X 
X 
X 
X 
X 
X 
Acceptance and Action Questionnaire 2 (AAQ-2) 
X 
X 
X 
X 
X 
X 
X 
 

Adherence to treatment (mediator) will be measured in the following ways: (1) Number of sessions attended; 
(2) Therapist ratings of homework compliance (0-100%) based on written assignment review and patient report 
after each session. Composite adherence score will be calculated on a 10-point Likert scale ranging from 0 
(Almost never/never adherent) to 10 (Always adherent). 
 
Timeline 
 
The first 3 months of the project are designed to hire staff, train clinicians, the blind raters, and VRAs 
(Table 3). There will be a total of 7 overlapping study waves, each lasting 12 months, in which we will enroll 9-
10 patients. During the last 3 months of the project, we will finalize data analysis, publish the results and 
determine the next step for competitive funding.  
 
 
 
 
 
Statistical Plan 
 
Missing data will be minimized by intensive training of the raters in techniques of clarifying answers and 
checking questionnaires while Veteran participants are on-site. When missing values are identified, several 
approaches to acquire the necessary data will be employed: (1) if at all possible, Veteran participants will be 
rescheduled within 24 hours of completion of tests or interviews; (2) if a participant cannot be rescheduled, an 
effort will be made to send a tester to the individual’s place of residence within the same period; (3) missing 
data will be examined to assess randomness. Missing data (i.e. loss to follow-up) will be tested to determine if 
it is informative, and the methods developed by Diggle87 and Ridout88 to test for completely random dropouts 
will be applied. If necessary, the techniques of Paik89 applicable to generalized estimating equations models 
will be used to impute missing values. However, the primary data analysis method allows inclusion of subjects 
with missing data or those who terminated the study early, without relying on data imputation procedures.  
Furthermore, we will test whether the drop-outs are random or systematic by comparing the drop-outs with the 
study completers on the baseline data. The importance of missing data will be examined in the second stage of 
data analysis (see below). 
Data analysis will be performed in multiple stages. In the initial stage, preliminary analyses will be 
performed by examination of the distribution of variables to assess their characteristics (means, standard 
deviations, and skewness). Descriptive statistics and graphs will used to summarize the characteristics of the 
study population. Continuous measures will be tested for normality and homogeneity of variance. Non-normally 
distributed variables will be transformed to meet the normal distribution assumption for linear models. 
Randomization will be assessed by performing a series of Wilcoxon-rank sum tests, Chi-square or Fisher’s 
exact tests to compare the groups on demographic and initial baseline clinical variables. Any variables on 
which the groups differ initially will be explored as covariates in subsequent analyses, and we will take this into 
account in the interpretation of the outcome. At the second stage, we will perform sensitivity analyses for the 
impact that potentially informative missing data may have on the analyses. We will use pattern-mixture models 
to assess if there is bias due to drop out or missing data. In addition, we will consider the extension of the 
pattern-mixture models as described by Guo, Ratcliffe, and Ten90, which includes the incorporation of random 
effects in the pattern-mixture model, which allow subject-to-subject heterogeneity.  
Wave 1: 10 ET; 10 CREST
Total: 10 ET; 10 CREST
Wave 2: 10 ET; 10 CREST
Total: 20 ET; 20 CREST
Wave 3: 10 ET; 10 CREST
Total: 30 ET; 30 CREST
Wave 4: 10 ET; 10 CREST
Total: 40 ET; 40 CREST
Wave 5: 10 ET; 10 CREST
Total: 50 ET; 50 CREST
Wave 6: 9 ET; 9 CREST
Total: 59 ET; 59 CREST
Wave 7: 9 ET; 9 CREST
Total: 68 ET;  68 CREST
Intervention (6 months) and follow-up (6 months)
Hire 
and 
train 
study 
staff
Recruitment, enrollment, and randomization
Analyze 
data and 
publish 
results
Table 3. Study Timeline 
Year 1
Year 2
Year 3
Year 4
Year 5

At the final stage, hypotheses will be tested using Mixed Effects models, a generalized linear model 
described by Gibbons et al.91, Hedeker et al.92 and Laird et al.93. Responses at baseline, throughout treatment 
(sessions 7, 13, 21), post treatment (session 26), 3- and 6-month follow-up will be nested within subjects. 
Intercept and slope will be modeled as random effects nested within subject; Treatment group, time, and 
group-by-time interaction will be a fixed effect. A fully saturated treatment by time model will be utilized for 
inference. Co-variance structure will be chosen based on Akaike’s Information Criterion (AIC). Data will be 
analyzed from all randomized subjects on whom we have a baseline assessment and at least one post-
baseline evaluation. If it is needed based on analyses on stage one, baseline covariates (e.g., demographics) 
will also be added to the model. All hypothesis tests will be intent-to-treat, and will be two-sided at the .05 level. 
We will adjust p-values for multiple testing within each hypothesis separately by using a Bonferroni correction 
whenever more than one variable is being tested. Although we didn’t have any drop-out in out pilot study, we 
included a drop-out rate of 10% after the baseline assessment but prior to the first post-baseline evaluation in 
our power analyses. 
 
Hypothesis 1.1-1.3: Relative to those assigned to ET alone, CREST participants will show significant 
reduction in hoarding severity (primary outcome), improvement in functioning (both functional capacity and 
self-reported functioning; secondary outcomes) and improvement in quality of life over time.  
 
Independent Variables: Treatment Groups (CREST and ET), Time points (baseline, throughout treatment 
(sessions 7, 13, 21), post-treatment (session 26), 3 and 6-month follow-up). 
Dependent Variable: Hoarding severity (SI-R), Functioning (UPSA, USORT, SLOF, WHODAS 2.0.), Quality of 
Life (Neuro-QOL). 
Statistical Analysis: The dependent variable will be analyzed by mixed effects model methods as described 
above. Baseline demographic and other clinically important characteristics at baseline will be assessed 
for imbalance between the two groups and their association with the outcome using a univariate 
analysis. Those found to be significantly unbalanced between intervention groups (p < 0.10) and 
moderately associated with the outcome (p < 0.15) will be included as covariates in the model. We will 
adjust p-values for multiple testing within each hypothesis separately by using a Bonferroni correction 
whenever more than one variable is being tested 
 
Hypotheses 2.1: Treatment adherence, improvement in executive functioning, and reduction in avoidance will 
mediate hoarding symptom reduction in CREST. 
 
Dependent Variables: Hoarding severity (SI-R) 
Independent Variables: Executive Functioning (D-KEFS scaled scores and PCET), Avoidance (AAQ and BAT) 
and Treatment Adherence score.  
Statistical Analysis: The effect of mediator variables will be tested following the procedures recommended by 
Kraemer94, Bauman95, Cohen and Cohen96, and Busemeyer and Jones97. Briefly, treatment mediators explain 
how or why one variable affects the treatment effect and are defined as mechanisms through which a 
treatment might achieve its effects. The mediator’s effect is measured during the treatment and is correlated 
with treatment choice and may possibly be a result of treatment and have either a main or interactive effect on 
the outcome. The dependent or outcome measure (SI-R) will be evaluated throughout the study and will be 
used as a repeated measure for all the available time points. In essence, the slope of each outcome measure 
on time will be used as a dependent measure. The mediation effect will be quantified by calculating the 
proportion of the treatment effect explained by the mediator and bootstrap technique will be used to calculate a 
95% confidence interval for mediation effect. Random effects models will be used for analysis and the change 
score of mediators will be included in the model. 
 
Hypotheses 2.2: Symptom severity reduction and improved functional capacity will mediate improved quality 
of life in CREST. 
 
Dependent Variables: Hoarding severity (SI-R), Functioning (UPSA, USORT, SLOF, WHODAS 2.0) 
Independent Variables: Quality of life (Neuro-QoL) 
Statistical Analysis: The effect of mediator variables will be tested similar to the hypothesis 2.1. 
 

Exploratory Aim 3: To explore age and baseline executive functioning as moderators in order to determine 
subpopulations in which CREST work best. 
Exploratory Aim 4: To examine time to maximum effect of treatment gains. 
 
These aims are focused on exploring on whom and under what conditions the treatment works best. These 
analyses may identify subpopulations with possibly different mechanisms and must be a baseline or pre-
randomization characteristic that could impact treatment outcome. We will focus on the moderator effect of age 
and baseline executive functioning and their interactions with treatment group. Age will be explored as 
continuous and ordinal (i.e. 45-55, 56-65, 66-75, 76-85) in format.  If the interaction effect is significant, 
pairwise comparisons of groups will be performed. These analyses will examine interactions of group with time 
at each level of the moderator, and evaluate treatment within each moderator subgroup. These exploratory 
aims will be examined using random effects regression analyses for each candidate moderator as a main 
effect and in interaction, similarly to methodology used for the hypothesis testing.  Furthermore, we will explore 
time to maximum effect of treatment gains (>35% reduction on SI-R) using survival analysis. The estimated 
survivorship curves will be obtained from Kaplan-Meier maximum likelihood estimates for each treatment 
group. The parameter estimates and 95% CI for the hazard ratio will be obtained from the Cox proportional 
hazards. Subjects who do not respond to treatment will be censored on their last visit date.  
 
Power Analysis  
Power analyses are performed for all hypotheses, incorporating the longitudinal nature of the design. Within 
this design, repeated observations within subjects are potentially correlated. This has a profound impact on the 
resulting tests of significance98. When the within subject correlation is properly incorporated, the repeated 
measures analysis takes full advantage of all information obtained from each subject, thereby greatly 
increasing statistical power over methods that compare treatments cross sectionally99. Using the method 
described by Diggle, Liang, & Zeger100 and Ahn et al.101, power calculations can be made for repeated 
measures designs under specified assumptions. Hedeker, Gibbons, & Waternaux102 extend Diggle et al.1-3’s 
method for various covariance structures.  Procedures describes by Hedeker et al.102 for Random Regression 
Models which incorporated these principles was used for the proposed study to estimated needed sample size 
(RMASS program provided by Hedeker for the Random Regression Model). The design assumptions consist 
of a 2 treatment groups and up to 7 visits (baseline, sessions 7, 13, 21, 26, and 3- and 6-month follow-up) 
where the slope is the dependent measure. Other assumptions used were alpha-level, nature of the hypothesis 
(two-sided versus one-sided), drop-out rate, and variance-covariance matrix of the longitudinal data. We 
assume a Type-I error level (alpha-level) of .01 to 0.05, drop-out rate of 15% and an autoregressive covariance 
structure. Data reported in the preliminary studies section which included our own pilot studies were used to 
calculate effect sizes. From the preliminary analysis of pilot study, the estimated standard deviation (SD) for SI-
R score ranges from 12.75-12.82 and the between visit correlation coefficient of 0.71. We considered a range 
of estimates of stand deviations of 12.5, 12.8 and 13.0, and correlations of .45 to 0.70 in our power analysis. 
We have reported large effect sizes of 1.02 and 1.51 from our previous studies which converted to differences 
of 60 to 37 for our primary outcome.  However, for these calculations, we conservatively selected smallest 
clinically meaningful differences that we would like to be able to detect. This was then converted to a medium 
effect size, defined mathematically as a between-group difference increasing linearly from 0 at baseline to .5 
SD units at the last time point. Calculations using the above assumptions indicated that the study will have 
minimum power of 80% to yield a statistically significant result for a medium effect size with the proposed 
sample size of 136 patients (68 for each of the two groups).