Reward Re-Training: A New Treatment to Address Reward Imbalance During the COVID-19 Pandemic
Phase: NA
Conditions: Bulimia Nervosa, Bulimia; Atypical, Binge Eating, Binge-Eating Disorder
Sponsor: Drexel University

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reward Re-Training: A New Treatment to Address Reward Imbalance During the COVID-19 Pandemic 
Study Protocol 
NCT04661410 
May 19, 2021 
 
 

RESEARCH STRATEGY 
A. Background and significance 
A.1. Public health approaches to combat COVID-19 have caused large disruptions in social networks. 
Public health approaches to reducing the spread of COVID-19 such as social distancing, shelter-in-place 
orders, quarantine, telework, and remote learning have produced a sudden and widespread disruption to social 
networks. These large disruptions to social networks are likely to increase social isolation (i.e.  
limited interactions, contacts, and relationships with family, friends, romantic partners, or co-workers) and 
loneliness (i.e. an adverse emotional state characterized by a lack of connection and intimacy),1 particularly for 
those living alone2 or those who already felt isolated before the outbreak.3  This is particularly concerning given 
the strong evidence that social isolation and loneliness are transdiagnostic risk factors for a range of mental 
health disorders4, strongly associated with increased risk of suicidality5, and have a comparable or greater 
impact on mortality than other common risk factors such as obesity, physical inactivity, and smoking.6   
A.2.  Social isolation can exacerbate mental health concerns by limiting opportunities to experience 
pleasure and reward during day-to-day life.     
We have long understood that social interactions are among the most powerful sources of pleasure and reward 
in day-to-day life.7-10  Yet, as noted above, during the COVID-19 pandemic, individuals are increasingly being 
encouraged or required to intentionally limit opportunities for social reward by staying at home and minimizing 
in-person contact with family, friends, classmates, and colleagues.11 Reduced exposure to sources of reward 
can lead to a hypo-reward response (e.g. low activation of dopaminergic cortico-striatal reward pathways) to 
conventionally rewarding stimuli11 (particularly to social stimuli and interactions12) and reduce an individual’s 
motivation to engage in activities that they usually find pleasurable.13 Motivation to engage in typically 
pleasurable activities will often continue to worsen over time as any engagement in activities that does occur is 
insufficiently reinforced due to the low levels of anticipatory and consummatory reward experienced.13 Thus, 
over time, a vicious cycle can occur such that day-to-day opportunities to experience reward become 
increasingly limited and anhedonia and depressed mood may begin or worsen.14 This cycle (depicted in blue 
text in Figure 1 below) has long been recognized as a maintenance factors for depression15-17 and disrupting 
this cycle is a key goal of effective treatment approaches for depression such as behavioral activation.18, 19  
A.3.  Low levels of day-to-day reward may also be a relevant maintenance factor for mental health 
conditions characterized by compulsive engagement in or use of highly rewarding stimuli.   
There is a growing body of evidence to suggest that insufficient reward from day-to-day life activities is a 
relevant maintenance factor for many mental health conditions beyond depression.20-24 In particular, mental 
health conditions characterized by compulsive engagement in or use of highly rewarding stimuli despite 
adverse consequences (e.g. substance use disorder, behavioral addictions, eating disorders) appear to be 
maintained, in part, by insufficient reward from day-to-day life activities.  When day-to-day life activities are not 
providing enough reward, these individuals may be more likely to seek out other stimuli that can immediately 
and powerfully activate neural reward pathways such as illicit substances or to over-indulge in naturally 
rewarding behaviors such as the consumption of palatable 
foods.25-27  A hyper-reward response (e.g. high activation of 
dopaminergic cortico-striatal reward pathways) to disorder 
specific stimuli (e.g. the feel of holding poker chips, the smell of 
highly palatable food, sexual imagery) may develop as individuals 
seek out larger quantities or more frequent exposure to a limited 
range of intensely stimulating sources of reward.  We propose 
that these individuals may become stuck in a second vicious 
cycle (depicted in green text in Figure 1) whereby increasing 
reliance on one behavior/substance to provide reward further 
reduces the ability to experience reward from day-to-day life 
activities, which then subsequently drives continued engagement 
in highly rewarding but risky behaviors. Together, the blue and 
green pathways in Figure 1 comprise what we have termed a 
reward imbalance.  While the reward imbalance is likely an 
important maintenance factor outside of the COVID-19 pandemic, 
the resulting disruptions to social networks are almost certainly 
exacerbating this cycle as depicted in Figure 1. 

A.4. The impact of COVID-19 on the reward imbalance underlying binge eating may be particularly 
pronounced and require targeted interventions.  
There is a strong and growing body of evidence supporting reward imbalance as an important maintenance 
factor for individuals with an eating disorders (ED) characterized predominately by binge eating episodes (i.e. 
eating a large amount of food within a discrete time period accompanied by a sense of loss of control over 
eating).  Individuals with bulimia nervosa (BN) and binge eating disorder (BED) show clear evidence of both 
insufficient reward from day-to-day-life activities (e.g. elevated rates of anhedonia21, 22, 28, 29) and a hyper-
reward response to palatable foods.30-33  Recent studies suggest that momentary assessment of constructs 
indicative of insufficient reward such as low levels of positive affect34-36 and bordeom37, 38 can predict increased 
risk for the near-time occurrence of a binge eating episode. Collectively, these results provide preliminary 
support for reward imbalance as a maintenance factor for binge eating.  
Individuals with EDs may also be particularly vulnerable to the disruption of social networks during COVID-19 
given the clear evidence that even before the pandemic, individuals with EDs were more likely to be socially 
isolated,39-41 spend more time alone,42 have greater rates of social anxiety,43 experience worse social 
functioning,44, and have worse quantity and quality of social support 45 compared to peers without an ED. 
Accordingly, there is emerging evidence suggesting an outsized impact of COVID-19 on ED symptoms46, 47 
likely due to the combined impact of heightened stressors, disrupted routines, and diminished social support 
paired with constant and easy access to food within the home that can trigger binge eating episodes. For 
example, in a recent study examining the impact of the first two weeks of stay-at-home orders on EDs, over 
50% of the sample reported heightened anxiety and nearly 40% reported a worsening of ED symptoms.48  
Accordingly, many individuals with EDs are urgently seeking additional treatment resources to cope with the 
new challenges they are experiencing. In March and April, the National Eating Disorders Association reported 
a 78 percent increase in people messaging its help line compared with the same period last year.49 Similarly, 
the Crisis Text Line, a nonprofit organization that provides mental health support by text, reported a 75 percent 
increase in conversations about eating disorders in the two months since March 16.49 These results align with 
our own experience of increased treatment seeking among individuals with EDs in recent months. For 
example, in response to an advertisement placed on Facebook in June 2020 about a fully remote group-based 
clinical trial for individuals with binge eating disorder (R01DK117072), we had 480 individuals complete our 
online interest survey in a 4-day time period, with over 130 individuals meeting preliminary eligibility criteria. 
The high level of interest in treatment has resulted in a large waitlist of likely eligible participants (see 
Recruitment and Retention Plan for more details). These results suggest a clear and pressing need to develop 
and deliver highly scalable treatment approaches for binge eating during the COVID-19 pandemic.  
A.5. Reward Re-Training: A novel intervention approach designed to alter the reward imbalance.   
Prior to the COVID-19 pandemic, our team began to develop and pilot a novel treatment approach called 
Reward Re-Training (RRT) that is specifically designed to address reward imbalance. Although we believe that 
RRT could be an effective treatment approach for numerous mental health conditions, we developed our initial 
version of RRT for individuals with transdiagnostic binge eating. RRT is designed to be a brief, 10-session 
group-based behavioral treatment. One unique aspect of RRT compared to traditional behavioral treatment 
approaches for EDs is that RRT does not directly attempt to reduce binge eating episodes via commonly used 
behavioral treatment components such as regular eating interventions and self-monitoring of food intake.50 
Instead, RRT is designed to indirectly change binge eating by directly focusing on building a more rewarding 
life.  RRT hypothesizes that reductions in binge eating will occur as life becomes more rewarding because 
individuals will no longer need to rely on binge eating as a primary source of momentary reward. RRT notes 
that in order to live a satisfying life, individuals need to experience an adequate amount of reward in two 
overlapping yet distinguishable domains: momentary reward (i.e., the active experience of pleasure in the 
moment) and sustained reward (i.e., a deeper and more long-lasting sense of fulfillment and meaning that 
arises from building a personally valued life). A key aspect of RRT is an emphasize on building lasting and 
meaningful social relationships given the clear evidence that social connectedness can enhance both 
momentary reward and sustained reward.7 
A.5.1. Increasing momentary reward outside of binge eating. RRT frames the use of binge eating as a source 
of momentary reward as risky since binge eating will 1) likely provide less momentary reward over time due to 
tolerance and habituation, 2) increase short-term negative affect (e.g. guilt, regret, and shame), and 3) 
undermine attempts to increase sustained reward by continuing the cycle depicted in Figure 1 above. Based 
on evidence that pleasant event scheduling (an evidence-based component of behavioral treatments for 

depression that seeks to increase momentary reward by increasing pleasant experiences, social activity, and 
completion of productive tasks18, 19) can improve anhedonia over time, we chose to use pleasant event 
scheduling as the starting point of RRT. Individuals are instructed to continue engaging in pleasant event 
scheduling even if the new activities do not immediately provide significant momentary reward by emphasizing 
the need to “re-train” reward networks away from eating and towards these new activities through repetition 
and practice. RRT also encourages the use of several additional cognitive and affective strategies designed to 
facilitate and enhance the ability to experience reward from conventionally rewarding activities. For example, 
RRT teaches patients how to shift attention towards positive momentary experiences and how to reframe 
affective experiences to allow room for multiple emotions.    
A.5.2. Enhancing sustained reward by building a personally valued life. RRT emphasizes that in order to truly 
correct the reward imbalance, we must identify what a satisfying and fulfilling life would look like and start to 
build a life that will feel personally valued. RRT uses techniques from evidence-based treatments like 
acceptance and commitment therapy51 to help an individual clarify his or her values (defined as global, desired 
and chosen life directions52) to inform the selection of behavioral patterns that will be built during treatment. For 
example, if an individual determines that he values supportive friendships but reports having few friendships 
currently, a major emphasis of treatment would be on identifying how to change his lifestyle to expand his 
social network and enhance the quality of his existing friendships. This work may include identifying new 
activities where he may be likely to meet individuals with shared interests, facilitating more frequent contacts 
with his current social connections, and learning social communication strategies to build greater intimacy 
within his friendships. RRT acknowledges that the process of building a life that will provide sustained reward 
will at times be difficult, uncomfortable, and distressing. In the above example, developing close and supportive 
friendships may be stressful or anxiety provoking and could introduce the possibility of rejection, none of which 
will feel pleasurable in the moment. RRT provides new techniques designed to make the process of pursing 
sustained reward also provide momentary reward. For example, RRT teaches individuals how to experience a 
sense of self-efficacy and personal achievement whenever he or she makes a difficult behavioral choice that 
supports the development of a valued life capable of providing sustained reward. In this way, RRT supports 
individuals in their pursuit of a valued life by ensuring that there is also sufficient momentary reward (e.g. 
achievement, confidence, pride) that can reinforce these new values-consistent behaviors.   
A.5.3. Increasing the quantity and quality of social interactions. When choosing pleasant events, RRT 
specifically encourages individuals to prioritize activities that are social in nature given evidence that these 
activities tend to be more enjoyable in the moment than solitary activities.10, 53  Similarly, given that for most 
individuals, meaningful and fulfilling relationships are among the most important valued life domains,8, 10 RRT 
particularly focuses on building valued life domains related to relationships (e.g. romantic relationships, family 
relationships, friendships). RRT also teaches skills focused on how to develop and maintain high quality 
relationships. These include strategies for making relationships deeper and more fulfilling, strategies for 
building intimacy in new relationships, and effective communication strategies.  Because many individuals with 
EDs are socially isolated and the development of meaningful relationships will take time, RRT is delivered in a 
group format and encourages the use of the group as an immediate source of social connection.  Group 
members are encouraged to develop relationships with each other outside of the group setting that may last 
well beyond the program’s short duration.   
A.6. Preliminary results of RRT suggest the promise of this intervention paradigm, but additional 
research is needed to determine whether a fully powered trial is worth pursuing.   
In a recent pilot study of RRT, we randomized 19 individuals with transdiagnostic binge eating to receive either 
RRT or a wait-list control. As described in greater detail in the Preliminary Studies section below, we found 
preliminary support for the feasibility, acceptability, target engagement, and clinical impact of RRT. However, 
despite the promise of our early pilot data, we believe that a more rigorous pilot RCT with an active control 
condition and with follow-up data would allow us to determine whether RRT is worth testing as a treatment 
approach for transdiagnostic binge eating in a fully powered clinical trial. We also believe that there is 
considerable benefit to leveraging our existing clinical research infrastructure (see Recruitment and Retention 
plan for additional details) to evaluate RRT during the COVID-19 pandemic given that RRT is particularly well-
suited to address the disruption to social networks and resulting impact on day-to-day reward that has occurred 
due to COVID-19. The proposed study is consistent with the research priorities outlined in NOT-MH-20-047 
(e.g. Research to identify potential intervention targets for modifying social connectedness, isolation, and/or 
loneliness via social media and/or electronic communication to prevent the development of clinically significant 
mental health symptoms.) 

A.7. Current study and specific aims.  
In the current study, we will revise our existing 10-session group RRT treatment manual to specifically address 
the challenges in building social support and enhancing both momentary and sustained reward during the 
COVID-19 pandemic (Preliminary Aim 1).  In months 2-18, we will conduct a small pilot RCT that will 
randomize individuals to receive either 10-sessions of RRT (n=30) or supportive therapy (n=30), both delivered 
as group-treatments via videoconferencing software. The specific aims of the current study are to confirm the 
feasibility and acceptability of RRT for EDs (Primary Aim 1), evaluate the ability of RRT to engage critical 
targets including reward to day-to-day life activities, reward to palatable foods, social isolation, and loneliness 
(Primary Aim 2), and provide preliminary estimates of efficacy in reducing ED symptoms at both post-treatment 
and a 3-month follow-up (Primary Aim 3).  We will also evaluate the impact of RRT on secondary outcome 
variables including depression, substance use, and quality of life (Secondary Aim 1). 
B. Innovation 
B.1. Treatment target innovation.  To the best of our knowledge, there are no other treatment approaches for 
EDs that have been empirically tested that specifically attempt to improve binge eating by increasing day-to-
day reward. To date, the closet evidence-based treatment approach is Interpersonal Therapy (IPT),54 an 
intervention approach initially developed for depression that focuses on addressing interpersonal difficulties 
and works via an indirect pathway to improve ED symptoms. Meta-analyses of IPT for EDs generally suggest 
that while IPT tends to work less rapidly than more directive behavioral treatment approaches like CBT, it 
eventually reaches similar levels of efficacy and may protect better against relapse.55  The success of IPT 
suggests that that it is possible to improve ED symptoms indirectly and that interventions focused on 
relationships can be effective in doing so. While IPT and RRT both address relationships, IPT is more narrowly 
focused on a specific set of relationship concerns (e.g. role disputes, role transitions, interpersonal deficits, 
and/or unresolved grief)54, which may reduce the degree to which IPT could improve day-to-day reward via 
improvements in social relationships.  RRT instead uses behavioral techniques to broadly focus on increasing 
momentary and sustained reward (often, but not entirely, by developing and improving social relationships) 
which may allow RRT to have even broader impact on ED symptoms.  
B.2. Clinical innovation.  As described above, RRT uses techniques from evidence-based treatments known 
to improve the ability to experience reward (e.g. pleasant event scheduling, values-based behavioral 
activation). RRT also shares features with other in-development treatment approaches that focus on increasing 
positive affect (e.g., positive affect treatment,56 mindfulness-oriented recovery enhancement57). However, RRT 
is distinct in four key ways: 1) RRT focuses on increasing both momentary and sustained reward, while the 
majority of other treatments primarily focus on increasing momentary reward; 2) RRT is designed for use in 
disorders characterized by compulsive engagement in or use of highly rewarding stimuli rather than mood 
disorders, which is where most of the work has been done to date for behavioral activation and positive affect 
focused treatments; 3) RRT contains new cognitive and affective strategies designed to support individuals in 
their pursuit of a valued life capable of providing sustained reward by helping the process of pursing sustained 
reward also provide momentary reward; 4) RRT specifically focuses on increasing the quantity and quality of 
social activities and relationships given evidence that support the high reward value of these domains.     
B.3. Dissemination and implementation innovations. While there is growing evidence that the provision of 
therapy via videoconferencing is an effective intervention modality,58 the majority of existing trials have tested 
individual psychotherapy which can be difficult to scale during times where there is a significant increase in 
treatment need.  The current study will be among the first to test the feasibility and acceptability of a short-term 
(e.g. 10 session) group-based videoconferencing treatment for EDs, which has high potential to be a 
disseminable and scalable treatment approach.  
C. Preliminary Studies  
C.1. Promising results from our prior studies demonstrate that 1) our hypotheses are likely to be 
supported, and 2) our team has the expertise necessary to conduct the proposed study.  
C.1.1 Feasibility and acceptability of delivering remote treatments for EDs. Our team transitioned three NIH-
funded clinical trials for BN and/or BED from in-person treatment to remote treatment in March 2020 due to the 
COVID-19 pandemic and since then have started two additional NIH-funded clinical trials that are fully remote. 
As outlined in greater details in the Recruitment and Retention Plan, we have been able to successfully 
transition to remote recruitment and enrollment and have seen increases in the number of individuals who are 
interested in participating in one of our clinical trials. In addition to high interest in remote therapy, we have also 

observed increases in our attendance and retention rates and similar efficacy with the switch over to remote 
treatment. For example, in our ongoing group-treatment study for individuals with BED (R01DK117072) we had 
a new wave of groups scheduled to start one week after the stay-at-home order was implemented for 
Philadelphia necessitating that all group session for this wave occur via teleconferencing. Surprisingly 
attendance rates for the first 10 sessions of this wave of groups have been higher than for in-person groups 
(96.5% vs. 85.0%), drop out was lower (5.0% vs.14.0%), and reductions in binge eating by the mid-treatment 
assessment were slightly better (87.3% reduction in binge eating episodes compared to 71.9% reduction). 
Overall, these results support the feasibility and acceptability of remote treatments for EDs and demonstrate 
that our team has developed the infrastructure to allow for a rapid start-up to the proposed project.  
C.1.2. Social isolation in individuals with BED during the COVID-19 pandemic. We administered a brief survey 
to individuals currently participating in R01DK117072 to assess the impact of public health initiatives to control 
the spread of COVID-19 on social networks (n = 21). The majority of our participants reported a significant 
reduction in both the frequency of social interactions (57.1%) and in satisfaction with their current relationships 
(61.9%) confirming that there have been widespread disruptions to social networks due to the COVID-19 
pandemic in our patients.  
C.1.3 RRT pilot trial. We recently conducted a small, proof-of-concept pilot 
trial where we randomized individuals with transdiagnostic binge eating 
(n=19) to receive either 10 weeks of group-based RRT or a wait-list control 
(WLC). RRT produced a significant reduction in binge eating episodes 
(Figure 2) and 40% of individuals in RRT were in remission by the end of 
treatment compared to 0% in WLC. Preliminary results support our targets 
with individuals who received RRT experiencing greater pleasure from social 
activities (Figure 3), more momentary reward during day-to-day life activities 
(Figure 4), and less reward to palatable foods (Figure 5). 
D. Approach 
D.1. Participants.  60 participants will be recruited for this study. Participants must: A.) be age 18-65, and B.) 
have a diagnosis of either BN or BED. Individuals will be excluded if they are 1) below a BMI of 17.5, 2) are 
already receiving treatment for an ED, 3) require immediate treatment for medical complications as a result of 
eating disorder symptoms, or 4) are experiencing other severe psychopathology that would limit the 
participants’ ability to comply with the demands of the current study (e.g. severe depression with suicidal intent, 
active psychotic disorder). Participants will be screened by phone to assess preliminary eligibility.  Phone 
screens will use questions from the Mini International Neuropsychiatric Interview (MINI)59 to assess psychiatric 
comorbidity and will be conducted by trained doctoral students, similar to procedures used successfully in our 
teams other NIH trials.  
D.2.  Refining RRT for use during the COVID-19 pandemic. In month 1, we will revise our existing RRT 
manual to facilitate delivery via videoconferencing software by applying “lessons learned” from our ongoing 
remote groups for R01DK117072. For example, we will add instructions to use video conferencing features 
such as breakout rooms to facilitate in-session experiential activities and whiteboards to facilitate ‘real-time’ 
collaborative problem-solving. We will also revise the content of the RRT manuals to provide guidance on ways 
to build and maintain social connections during the COVID-19 pandemic as in-person social contact is limited 
(e.g., connecting with neighbors on Facebook group, scheduling virtual game nights with friends, enhancing 
intimacy with romantic partners during at home dates, attending virtual happy hours with colleagues), and 
address disruptions in current relationships due to the pandemic (e.g., conflict due to the switch to telework/ 
teleschool). Participants will be encouraged (though not required) to connect with each other outside of group 
using email, texting, and social networking platforms to enhance social support outside of weekly sessions.  

D.3. Supportive therapy as an active control condition. We considered several possible comparison 
conditions for the proposed trial including treatment-as-usual, the provision of self-help reading materials, and 
the use of a gold-standard comparison such as CBT before determining that a group-based supportive therapy 
condition was the best control condition for the current state of the research. Supportive therapy will allow us to 
control for many of the non-specifics of therapy such as working with an empathetic provider and instilling hope 
and optimism. The group-nature of the supportive therapy condition will also allow us to better determine 
whether treatment gains were due to the content of RRT or if comparable gains can be achieved by simply 
increasing social connection and support via a group treatment.  The supportive therapy condition will be 
based on existing manuals.60 As is typical for supportive therapy conditions, the group leader will be instructed 
to be non-directive and allow the patients to determine the focus of each session.61 The group leader will be 
encouraged to use reflective listening, elicit and validate affect, and offer empathic comments. Group leaders 
will also be instructed to avoid any cognitive and behavioral techniques that could overlap with RRT.   
D.4. Treatment facility, clinicians, training, supervision, competence and fidelity.  All treatment for the 
study will be provided by clinicians from the WELL Center Clinic (see Facilities for more details), an outpatient 
community clinic serving the Philadelphia metropolitan area. Weekly clinical supervision will be provided 
throughout treatment by Dr. Srivastava who will remain unblinded to allow her to provide clinical supervision. 
To maximize fidelity, we will use treatment manual which are designed for easy use during group treatment 
sessions.  All treatment groups will be audio recorded, and an independent evaluator (a doctoral student with 
intensive training) will independently monitor and rate treatment competence and fidelity for 25% of group 
sessions for both conditions.   
D.5. Remote study procedures. Study assessments and group therapy sessions will be conducted using an 
encrypted HIPAA-compliant version of Zoom videoconferencing software which we are currently using in 
several NIH-funded clinical trials during the stay-at-home orders. Informed consent will be collected using an 
electronic consent form that participants will be asked to complete during the appointment after reviewing the 
consent form jointly with a staff member.  
D.6. Assessments. Assessments will be conducted by blinded assessors at baseline, mid-treatment (after 
session 5), post-treatment (after session 10), and at a 3-month follow-up. Our assessment strategy was 
specifically designed to allow for remote assessment during the COVID-19 pandemic and thus will only include 
measures that can be completed using videoconferencing or via the participants home computer. In order to 
maximize assessment completion, we will increase compensation across assessments ($50, $75, $100, $125).  
D.6.1. Feasibility and Acceptability. Assessment of feasibility will include % of eligible patients enrolled, 
attrition, and study retention. We will use a Feedback Questionnaire (FQ) to obtain qualitative acceptability 
ratings, which will be modified from FQs used in our prior intervention development projects.  
D.6.2. Primary outcomes. The Eating Disorder Examination62 is a widely utilized, semi-structured interview for 
the assessment of eating disorder symptoms. We will use number of binge episodes in the last 28 days and 
EDE global scores as the primary outcomes. Remission status will also be evaluated at each assessment 
following the baseline assessment and will be defined as the absence of any binge episodes or compensatory 
behaviors in the 28 days prior to the assessment point and an EDE global score within 1 standard deviation of 
the community norm (EDE global <1.74).50  
D.6.3. Secondary outcomes. We chose to use commonly-used and well-validated measures of depression 
(Beck Depression Inventory-II63), substance use (Alcohol, Smoking, and Substance Involvement Screening 
Test64), and quality of life (Quality of Life Inventory65) to assess secondary outcome measures.  
D.6.4. Target engagement. We chose to use the same measures of target engagement that we used in our 
pilot trial to determine whether our pilot results will replicate when compared to a more stringent control 
condition. We will use the Power of Food Scale (PFS)66 to assess reward response to palatable foods, and the 
Temporal Experience of Pleasure Scale (TEPS)67  and Dimensional Anhedonia Rating Scale68 to measure 
anticipatory and consummatory experiences of pleasure to day-to-day life activities. Additionally, we will also 
include measures of social support, companionship and social distress from the NIH Toolbox Social 
Relationship Scales Assessment Battery69 to better assess the impact of RRT on social isolation and 
loneliness as additional targets.  
D.7. Statistical analyses.  A full description of the statistical analyses and power considerations can be found 
in the clinical trial supplement document Statistical Design and Power. 
 

 
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