Acceptance and Commitment Training for Adolescents and Young Adults With Neurofibromatosis Type 1, Plexiform Neurofibromas, and Chronic Pain: A Phase III Clinical Trial
Phase: PHASE3
Conditions: Neurofibromatosis Type 1, Plexiform Neurofibromas
Sponsor: National Cancer Institute (NCI)

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Abbreviated Title:  ACT Therapy for NF1Related Pain 
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Abbreviated Title: ACT Therapy for NF1Related Pain 
CC Protocol #: 15-C-0142 F 
Version Date: 02/19/2019 
NCT Number: NCT02471339 
Title: Acceptance and Commitment Training for Adolescents and Adults with 
Neurofibromatosis Type 1, Plexiform Neurofibromas, and Chronic Pain: A Phase III Clinical 
Trial 
NCI Principal Investigator:   
Staci Martin Peron, Ph.D.A-E 
Psychology Group 
Behavioral Health Core 
Pediatric Oncology Branch, CCR, NCI 
Building 82, Room 107, MSC 8200 
9030 Old Georgetown Road 
Bethesda, MD 20892-8200 
Phone: (240) 760-6025 
martins@mail.nih.gov 
 
Investigational Agents: N/A 
Commercial Agents: N/A 
 
 
 

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PRÉCIS   
Background: 
• Neurofibromatosis type 1 (NF1) is a genetic disorder that affects approximately 1 in 
3,500 individuals.  
• A number of common clinical manifestations, including plexiform neurofibromas, can 
cause frequent and significant pain and impact quality of life. 
• Often, NF1-related pain is not well-controlled with medication and many of the 
medications cause significant side effects. 
• To our knowledge, only one prior study (by our group) has examined the effectiveness of 
a psychological intervention for chronic pain in adolescents and young adults (AYA) 
with NF1. 
• Acceptance and Commitment Therapy (ACT), a “newer generation” of cognitive-
behavioral therapy, focuses on encouraging individuals to engage in more adaptive ways 
of coping with pain.   
• The goal of ACT is not to eliminate the person’s pain, but to optimize the person’s 
functioning despite their pain. 
Objective: 
• To compare pain interference mean score changes from baseline to 8 weeks between the 
ACT intervention group and the waitlist (WL) group. 
Eligibility: 
• Patients 16 – 59 years of age with a confirmed diagnosis of NF1 and >1 plexiform 
neurofibroma (PN). 
• The patient must obtain a mean score of 2.0 or higher or a score of 3 on three or more 
items on the Pain Interference Index, and report having pain that interferes with 
functioning for at least three months.   
• The patient must have regular access to a computer or tablet with internet access. 
Design: 
• This is a psychological intervention study to determine the potential benefit of ACT on 
pain interference, with patients randomized to the ACT intervention or a wait-list control 
group.  
• Patients will come to the NIH for a 2-day visit (Time 1). After baseline assessments 
(questionnaires and ECG) are completed, participants in the ACT group will take part in 
two 2-hour ACT training sessions.  At home, this group will receive weekly emails 
through week 8, and will participate in further ACT training/educational sessions via 
video chat at weeks 2, 4, and 6.   
• All patients will return to the NIH at week 8 (Time 2) to complete follow-up 
questionnaires and ECG.  At this time, the WL group will cross over and receive the ACT 
intervention (in-person sessions, weekly emails, and video chat sessions).  All patients 
will complete questionnaires again from home six months following the completion of 
the intervention.  
• To detect a change of .68 standard deviation on the primary outcome measure between 
the two groups at .80 power, 41 patients per group are needed.  
 

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TABLE OF CONTENTS 
PRÉCIS .......................................................................................................................................... 2 
TABLE OF CONTENTS ................................................................................................................ 3 
1 
INTRODUCTION .................................................................................................................. 7 
1.1 
Study Objectives .............................................................................................................. 7 
1.1.1 
Primary Objective ..................................................................................................... 7 
1.1.2 
Secondary Objectives................................................................................................ 7 
1.2 
Background and Rationale ............................................................................................... 7 
1.2.1 
Pain in Neurofibromatosis Type 1 (NF1) ................................................................. 7 
1.2.2 
Acceptance and Commitment Therapy ..................................................................... 8 
1.2.3 
Rationale for the Proposed Study ........................................................................... 12 
1.2.4 
General Overview ................................................................................................... 13 
2 
ELIGIBILITY ASSESSMENT AND ENROLLMENT ....................................................... 15 
2.1 
Eligibility Criteria .......................................................................................................... 15 
2.1.1 
Inclusion Criteria for Participant ............................................................................ 15 
2.1.2 
Exclusion Criteria for Participant ........................................................................... 16 
2.1.3 
Recruitment Strategies ............................................................................................ 16 
2.2 
Screening Evaluation...................................................................................................... 16 
2.2.1 
Pain level ................................................................................................................. 16 
2.2.2 
History and Physical Examination .......................................................................... 17 
2.3 
Registration Procedures.................................................................................................. 17 
2.3.1 
Treatment Assignment and Randomization/Stratification Procedures ................... 17 
2.4 
Baseline Evaluation ........................................................................................................ 18 
3 
STUDY IMPLEMENTATION ............................................................................................ 19 
3.1 
Study Design .................................................................................................................. 19 
3.1.1 
Baseline ................................................................................................................... 19 
3.1.2 
Follow-up ................................................................................................................ 20 
3.2 
ACT Intervention ........................................................................................................... 20 
3.2.1 
Therapist Training ................................................................................................... 20 
3.2.2 
ACT Training Content ............................................................................................ 21 
3.3 
Questionnaires ................................................................................................................ 23 
3.3.1 
Patient Questionnaires ............................................................................................ 23 

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3.3.2 
ECG procedures ...................................................................................................... 25 
3.3.3 
Word Reading test................................................................................................... 26 
3.4 
Study Calendar ............................................................................................................... 27 
3.5 
Compensation ................................................................................................................. 27 
3.6 
Criteria for Removal from Protocol ............................................................................... 27 
3.6.1 
Off-Study Procedure ............................................................................................... 28 
4 
DATA COLLECTION AND EVALUATION ..................................................................... 28 
4.1 
Data Collection ............................................................................................................... 28 
5 
SAFETY REPORTING REQUIREMENTS/DATA AND SAFETY MONITORING PLAN
 
28 
5.1 
Definitions ...................................................................................................................... 28 
5.1.1 
Adverse Event ......................................................................................................... 28 
5.1.2 
Suspected adverse reaction ..................................................................................... 29 
5.1.3 
Unexpected adverse reaction .................................................................................. 29 
5.1.4 
Serious..................................................................................................................... 29 
5.1.5 
Serious Adverse Event ............................................................................................ 29 
5.1.6 
Disability ................................................................................................................. 29 
5.1.7 
Protocol Deviation (NIH Definition) ...................................................................... 29 
5.1.8 
Non-compliance (NIH Definition) .......................................................................... 29 
5.1.9 
Unanticipated Problem............................................................................................ 30 
5.2 
NIH Intramural IRB and Clinical Director Reporting ................................................... 30 
5.2.1 
NIH Intramural IRB and NCI CD Expedited Reporting of Adverse Events, 
Unanticipated Problems, and Deaths .................................................................................... 30 
5.2.2 
NIH Intramural IRB Requirements for PI Reporting of Adverse Events at 
Continuing Review ............................................................................................................... 30 
5.3 
Data and Safety Monitoring Plan ................................................................................... 31 
5.3.1 
Principal Investigator/Research Team .................................................................... 31 
6 
STATISTICAL SECTION ................................................................................................... 31 
6.1 
Primary and Secondary Outcomes ................................................................................. 31 
6.2 
Subject Accrual .............................................................................................................. 32 
7 
HUMAN SUBJECTS PROTECTIONS ............................................................................... 32 
7.1 
Rationale For Subject Selection ..................................................................................... 32 
7.2 
Participation of Children ................................................................................................ 32 

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7.3 
Participation of Subjects Unable to Give Consent ......................................................... 32 
7.4 
Evaluation of Benefits and Risks/Discomforts. ............................................................. 33 
7.5 
Consent and Assent Process and Documentation .......................................................... 33 
7.5.1 
Request for waiver of consent for screening evaluation ......................................... 34 
7.5.2 
Consent for minors when they reach the age of majority ....................................... 34 
7.5.3 
Telephone consent .................................................................................................. 35 
7.5.4 
Telephone assent ..................................................................................................... 35 
8 
REFERENCES ..................................................................................................................... 36 
9 
APPENDICES ...................................................................................................................... 45 
9.1 
Appendix A: Screening Phone Calls to Determine Eligibility ....................................... 45 
9.2 
Appendix B: Adult Background Information Form ....................................................... 48 
9.3 
Appendix C: Adult Pain Questionnaire .......................................................................... 50 
9.4 
Appendix D: Pain Interference –Short Form 8a -Adult ................................................. 51 
9.5 
Appendix E: Pain Interference –Short Form 8a –Pediatric ............................................ 52 
9.6 
Appendix F:  PedsQL Neurofibromatosis Type 1 Module ............................................ 53 
9.7 
Appendix G:  Pain Anxiety Symptoms Scale-20 (PASS-20) ........................................ 57 
9.9 
Appendix H:  Center for Epidemiological Studies-Depression Scale (CES-D .............. 59 
9.10 Appendix I: Numeric Rating Scale-11 (NRS-11) .......................................................... 60 
9.11 Appendix J: Chronic Pain Acceptance Questionnaire (CPAQ) ..................................... 61 
9.12 Appendix K: Psychological Inflexibility in Pain Scale (PIPS) ...................................... 63 
9.13 Appendix L: Life Events Checklist ................................................................................ 65 
9.14 Appendix M:  Pain Management Inventory ................................................................... 67 
9.15 Appendix N:  Pain Management Inventory.................................................................... 68 
9.17 Appendix O: ACT Inventory.......................................................................................... 70 
9.18 Appendix P: Global Impression of Change Scale .......................................................... 72 
9.19 Appendix Q: ACT Workbook ........................................................................................ 73 
9.20 Appendix R:  Practice Exercises .................................................................................... 84 
9.21 Appendix S: Video Chat Manual ................................................................................... 88 
9.23 Appendix S: Acceptance and Commitment Therapy Core Competency Self-Rating 
Form 96 
9.25 Appendix T: Treatment Fidelity Checklist................................................................... 101 
9.27 Appendix U:  ACT Manual .......................................................................................... 102 

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9.28 Appendix V:  Recruitment E-mails .............................................................................. 108 
9.28.1 NCI Patient E-mail ................................................................................................ 108 
9.28.2 Recruitment E-mail CTF Registry ........................................................................ 109 
9.29 Appendix W:  Recruitment Flyer ................................................................................. 110 
 
 
 

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1 
INTRODUCTION 
1.1 
STUDY OBJECTIVES 
1.1.1 Primary Objective 
1.1.1.1 To evaluate whether patients receiving an Acceptance and Commitment Training 
(ACT) intervention demonstrate improved outcomes on a measure of pain interference 
(Pain Interference Index) when compared to a wait-list comparison group from baseline 
to 8 weeks (immediately post-intervention) in adolescents, and adults with NF1 and 
PNs who experience chronic pain that interferes with daily functioning.   
1.1.2 Secondary Objectives 
1.1.2.1 To examine baseline to 8-week changes in disease-specific quality of life, pain severity, 
pain-related anxiety, depression, and heart rate variability in patients receiving the ACT 
intervention.   
1.1.2.2 To examine between-group differences in disease-specific quality of life, pain severity, 
pain-related anxiety, depression, and heart rate variability from baseline to 8 weeks.  
1.1.2.3 To examine patterns of change from baseline to 8 weeks to 32 weeks in all primary and 
secondary outcome measures.   
1.1.2.4 To examine potential mediators between pre- and post-treatment pain interference, 
including pain acceptance, psychological flexibility, as well as cognitive diagnosis 
(ADHD, LD), disease characteristics (stable vs. progressive disease, location of 
plexiform neurofibroma), and recent life events to determine whether these variables 
influence the effectiveness of the intervention.   
1.1.2.5 To compare the reliability and validity of the two pain interference measures: the Pain 
Interference Index (PII) and the PROMIS Pain Interference scale.     
1.2 
BACKGROUND AND RATIONALE 
1.2.1 Pain in Neurofibromatosis Type 1 (NF1) 
Neurofibromatosis type 1 (NF1) is a genetic disorder caused by a mutation on chromosome 17 
and affects approximately 1 in 3,500 individuals (Tonsgard, 2006).  The disease is an autosomal 
dominant condition, and about half of cases arise from spontaneous mutations.  Males and 
females are equally represented (North, 2000). Many patients are diagnosed during the first year 
of life, often due to the presence of café au lait macules.  Typically, the frequency and severity of 
symptoms increases with age.  The clinical presentation varies considerably, within and between 
patients (Rieley et al., 2011). Symptoms and complications include plexiform neurofibromas 
(PNs), café au lait spots, optic pathway gliomas, short stature, Lisch nodules, scoliosis, 
malignant peripheral nerve sheath tumors (MPNSTs), as well as cognitive deficits, learning 
disabilities, and social-emotional problems (Hyman, Shores, & North, 2006; Tonsgard, 2006).   
Several clinical manifestations of NF1 can cause associated pain.  Most importantly for this 
study, PNs are benign tumors comprised of a proliferation of cells in the nerve sheath (Friedrich, 
Schmelzle, Hartmann, Funsterer, & Mautner, 2005; Gutmann et al., 1997).  Present in 30 to 50% 
of patients with NF1, PNs often exhibit rapid growth during childhood and adolescence but can 
occur at any age (Dombi et al., 2007; Tucker et al., 2009). These tumors can be internal without 
any visible indications, or they can be external and notably disfiguring.  Further, PNs often cause 

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significant pain that interferes with functioning (Kim et al., 2009; Wolters et al., in press), and 
negatively impact quality of life (QOL) (Wolkenstein et al., 2009).  
While this protocol will include only individuals with PNs, these patients may have co-existing 
symptoms that cause pain in NF1, such as headaches (DiMario & Langshur, 2000), scoliosis and 
its treatments (Jett & Friedman, 2010; Weiss, 2003), pseudoarthrosis (Georgescu et al., 2007; 
Tonsgard, 2006), glomus tumors (benign tumors of the fingers and toes; (Brems et al., 2009)), 
and gastrointestinal complications (Heuschkel, Kim, Korf, Schneider, & Bousvaros, 2001). 
The various conditions and symptoms described above emphasize the difficulties experienced by 
patients with NF1.  Not surprisingly, more severe symptoms, including pain, were associated 
with worse QOL among 170 adults with NF1 (Page et al., 2006).  Similarly, a previous study by 
our group (Burns et al., 2011a) noted that more severe pain correlated with worse QOL in 54 
children and adolescents with NF1 and PNs.  Further, more severe pain was found among the 
children with at-risk or clinically significant levels of depression and anxiety.  There are ongoing 
efforts to develop and investigate chemotherapeutic agents, a few of which are promising.  
However, at present the main treatment is surgical removal of the tumors, which is often 
complicated by the involvement of nearby nerve tissue, and tumor regrowth is common (Jett & 
Friedman, 2010).  Symptoms can be managed with pain medication, including nonsteroidal anti-
inflammatory drugs (NSAIDs), anticonvulsants, and narcotics; however, many patients taking 
these medications experience side effects (Rainsford, 1999; Rodriguez et al., 2008; Swann, 2001) 
and continue to report pain (Burns et al., 2011a; Kim et al., 2009). While one study with adults 
examined a psychological intervention for patients with NF1, the study also included individuals 
with NF2 and schwannomatosis, and not all patients with NF1 had PNs (Vranceanu, Merker, 
Plotkin, & Park, 2014).  In terms of adolescents with NF1 and PNs, only one psychological 
intervention (ACT) for pain coping has been conducted to our knowledge (Martin et al., 
manuscript accepted).  
1.2.2 Acceptance and Commitment Therapy 
1.2.2.1 General Overview 
Acceptance and Commitment Therapy (ACT) is one of the newer generations of cognitive-
behavioral therapy (CBT) that has been used successfully to treat individuals with pain.  One of 
the core therapeutic foundations of ACT is mindfulness, which is defined as “nonjudgmental, 
moment-to-moment awareness” (Kabat-Zinn, 1990).  A broad research base strongly supports 
the effectiveness of mindfulness-based techniques for the improvement of psychological 
functioning and amelioration of symptoms such as anxiety and depression (Chiesa & Serretti, 
2011; Hofmann, Sawyer, Witt, & Oh, 2010).  The effects of mindfulness have been shown to last 
for up to four years (Kabat-Zinn, Lipworth, Burney, & Sellers, 1986) and its practice 
significantly reduces the risk of relapse or recurrence, for example, among depressed patients 
(Piet & Hougaard, 2011; Teasdale et al., 2000).  A review article concluded that participation in 
mindfulness-based programs aimed at reducing stress improves coping and QOL in medical 
populations (Merkes, 2010).  Moreover, several studies have pointed to neurobiological changes, 
such as prefrontal activation and increases in gray matter concentration in the hippocampus, that 
occur over extended mindfulness practice (Chiesa & Serretti, 2010; Holzel et al., 2011).   
ACT is a therapeutic model that has grown out of CBT traditions and the mindfulness literature.  
It focuses on encouraging individuals to gain psychological flexibility so they can engage in 

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more adaptive ways of coping with emotional or physical pain.  The underlying premise is that, 
in many situations, attempting to control one’s pain or problems is futile and can lead to the 
individual focusing a huge amount of their energy on a useless endeavor. As opposed to 
traditional CBT, which attempts to change people’s irrational or negative thoughts, ACT uses 
mindfulness to help people become aware of their thoughts and accept them without judgment.  
When people increase their awareness of their thoughts, they are able to change their relationship 
with those thoughts, and not let the thoughts dictate their behavioral response.  When individuals 
learn that they do not have to act upon their thoughts, they can then re-focus their energy toward 
engaging in behaviors that are in line with their core values and thus lead a more fulfilling life 
(Hayes, Strosahl, & Wilson, 1999).  
During the past decade, ACT techniques have been applied to a wide range of presenting 
problems such as depression (Forman, Herbert, Moitra, Yeomans, & Geller, 2007), Post-
Traumatic Stress Disorder (Walser & Westrup, 2007), Obsessive-Compulsive Disorder (Twohig, 
Hayes, & Masuda, 2006), smoking cessation (Hernandez-Lopez, Luciano, Bricker, Roales-Nieto, 
& Montesinos, 2009) and pain (L. M. McCracken, Vowles, & Eccleston, 2004; Wicksell, Melin, 
Lekander, & Olsson, 2009a), all with promising results.  The effectiveness of ACT has been 
demonstrated when the treatment was administered via weekly sessions (Masuda, Cohen, 
Wicksell, Kemani, & Johnson, 2011; Wicksell, Melin, & Olsson, 2007) and in 1- or 2-day group 
workshops (Bach & Hayes, 2002; Butryn, Forman, Hoffman, Shaw, & Juarascio, 2011; Dahl, 
Wilson, & Nilsson, 2004; Pearson, Follette, & Hayes, 2011). In addition, in 2011, ACT was 
classified as having “strong empirical support” by the United States Substance Abuse and Mental 
Health Services Administration (nrepp.samhsa.gov).  It is currently the only psychological 
therapy to have earned that designation.   
1.2.2.2 The Use of ACT with individuals with chronic pain 
In using ACT to help individuals with chronic pain, the goal is not to eliminate the person’s pain, 
but to help the person achieve and maintain a high QOL while living with their pain.  More 
specifically, patients are taught to notice their thoughts about their pain from a more neutral 
perspective, without necessarily acting upon them.  Patients are then encouraged to consider their 
individual values and the way in which pain is interfering with leading a values-consistent life. 
For example, a patient may place a high value on their education, but may not spend as much 
time studying or attending classes as they would like due to their pain.  They may have the 
thought “I have too much pain to go to class today,” and then consequently avoid the associated 
behavior (i.e., going to class).  When a person learns to notice those thoughts through 
mindfulness and related processes, they can then respond to those thoughts in accordance with 
their values while accepting the fact that they may experience pain in the process (e.g., go to 
class despite the pain).  
Researchers have produced numerous studies supporting the effectiveness of ACT in individuals 
with chronic pain, including patients with severe debilitating pain (L. M. McCracken, 
MacKichan, & Eccleston, 2007).  One study (Wicksell et al., 2013) randomly assigned women 
with fibromyalgia to an ACT intervention or a wait-list control condition.  After 12 weekly group 
sessions, participants in the ACT arm demonstrated significant improvements in pain-related 
functioning, self-efficacy, depression, and anxiety, compared to the control group.  In similar 
studies, ACT has been compared to relaxation training and treatment as usual, with results 

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favoring the ACT groups on measures of pain-related disability, pain acceptance, depression, and 
overall satisfaction with life (L. M. McCracken, Sato, & Taylor, 2013; Thorsell et al., 2011).   
It should be noted that some studies have found ACT to be comparable to CBT.  In a study of 
114 adults with chronic pain, including osteoarthritis and neuropathic pain, ACT was compared 
with traditional CBT over eight weeks of small group sessions (Wetherell et al., 2011).  Results 
indicated significant improvements over time on pain interference, depression, and pain-related 
anxiety in both the ACT group and the CBT group.  While there were no differences between the 
two groups on any of the primary outcome measures, participants in the ACT group reported a 
higher level of satisfaction with treatment at the end of the intervention.  Overall, ACT is 
considered at least as effective as, and sometimes superior to, traditional therapies.  
The use of ACT with individuals with chronic pain also has important implications for healthcare 
costs.  Researchers in Sweden (Dahl et al., 2004) examined the effects of an ACT intervention on 
usage of sick leave and medical resources among public health employees considered at-risk for 
chronic pain and medical leave.  Participants were randomized to receive four 1-hour sessions of 
ACT plus usual medical treatment, or usual medical treatment only.  In the six months following 
the intervention, the ACT group utilized fewer sick days and fewer medical treatment resources 
than the comparison group.  No pre-post differences were seen in QOL among either group.  
However, these results point to the potential for ACT to have a widespread economic impact.   
ACT also has demonstrated effectiveness with adolescents with chronic pain.  For example, one 
study (Wicksell et al., 2009a) utilized an ACT intervention with children and adolescents with 
long-term idiopathic pain.  The children participated in ten weekly 1-hour sessions, and their 
parents participated in one to two 90-minute sessions.  A comparison group of patients received a 
multidisciplinary treatment consisting of relaxation and imagery techniques, physiotherapy, and 
amitriptyline.  Patients in the ACT group showed significant improvements from baseline to 3- 
and 6-month follow-ups in pain-related functioning according to both parent and child 
questionnaires.  They also reported significantly less pain interference and better health-related 
QOL at follow-up.  Compared to the multidisciplinary treatment group, the ACT group improved 
more with respect to pain impairment beliefs, pain intensity, and pain-related discomfort.  The 
ACT group also showed less depressive symptoms at follow-up than the comparison group, 
although this difference was not statistically significant.      
Finally, in 2011 a meta-analysis examined the effectiveness of ACT and other mindfulness-based 
interventions (collectively) among 19 studies of patients with chronic pain (Veehof, Oskam, 
Schreurs, & Bohlmeijer, 2011).  Moderate, significant effect sizes were found for the impact of 
ACT on pain intensity, depression, anxiety, and QOL.  The authors concluded that ACT has 
positive effects on physical and mental health among patients with chronic pain, and they cite the 
need for more scientifically sound studies to further this area of research. 
1.2.2.3 Mediators of Treatment Efficacy  
Recent publications have called for psychological intervention studies to include an examination 
of process variables, or the factors that may mediate the effectiveness of the intervention. The 
two process variables thought to be most relevant to ACT and chronic pain are pain acceptance 
and psychological flexibility.  Acceptance of pain refers to a person’s willingness to live with 
their pain as opposed to taking the stance that their pain must remit before they can live their life 
(L. McCracken & Zhao-O'Brien, 2010). In a study of adults with chronic pain, researchers 

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determined that changes in acceptance following an ACT intervention accounted for unique 
variance on all outcome measures, including pain-related disability, depression, anxiety, and 
performance on a timed-walk task (Baranoff, Hanrahan, Kapur, & Connor, 2013).  Further, in 
adults with HIV disease and chronic pain, increases in pain acceptance during a 12-week ACT 
intervention were correlated with decreased pain-related impairment (Huggins, Bonn-Miller, 
Oser, Sorrell, & Trafton, 2012).   
With respect to psychological flexibility as a process variable, Wicksell, et al. showed that the 
effectiveness of an ACT intervention in patients with chronic pain was mediated by variables 
consistent with psychological flexibility (Wicksell, Olsson, & Hayes, 2011).  Vowles and 
McCracken (2010) examined effects of an ACT treatment on measures such as depression, 
anxiety, and physical functioning.  They found that changes in psychological flexibility 
accounted for significant variance in most outcomes, while changes in more traditional pain 
management processes (e.g., distraction, relaxation, physical exercise) did not.  The authors 
suggest that psychological flexibility should be considered as central to future investigations of 
chronic pain and relevant interventions (Vowles & McCracken, 2010).   
1.2.2.4 Internet-delivered ACT 
In recent years, mental health interventions have increasingly explored technological methods of 
delivery.  Researchers are administering psychological treatments via email, online therapeutic 
materials, and smartphone applications with encouraging findings (Espie et al., 2012; 
Kirkpatrick, Manoukian, Dear, Johnston, & Titov, 2013; Swendeman, Comulada, Ramanathan, 
Lazar, & Estrin, 2014). In line with recommendations from a 2012 review article (Leykin et al., 
2012), several studies have implemented ACT interventions via the internet.  For example, one 
study randomized chronic pain outpatients to participate in seven weeks of an internet-guided 
ACT treatment or an online discussion forum about chronic pain (Buhrman et al., 2013).  
Findings were in favor of the ACT group on measures of pain interference, pain acceptance, 
anxiety, depression, and catastrophizing, with effects maintained six months post-treatment.  
Another study randomly assigned participants with chronic pain to an internet-guided ACT 
intervention, an online expressive writing intervention, or a wait-list control condition 
(Trompetter et al., 2014).  Again, ACT group participants generally showed superior 
improvements on measures of pain interference, depression, and pain-related disability.  
Video chat sessions have been utilized in a small number of studies involving individuals with 
medical conditions.  These studies have been aimed at, for example, reducing sedentary behavior 
among individuals with multiple sclerosis (Klaren, Hubbard, & Motl, 2014) and increasing 
adherence among adolescents with poorly controlled diabetes (Freeman, Duke, & Harris, 2013).  
In addition, video chat was used in a recent study investigating effectiveness of an acceptance-
based therapy similar to ACT, and the intervention was rated as feasible by the participants and 
therapists (Yuen et al., 2013).  Technologies such as these are rapidly becoming common modes 
of administering psychological interventions among a wide variety of patient populations.  
However, video chatting has not been used in any published studies including patients with NF1.   
1.2.2.5 Heart Rate Variability 
The interaction between neural structures involved in pain perception and automatic nervous 
system (ANS) function are central to the process of pain regulation (Benarroch, 2006). Heart rate 
variability (HRV) is a physiological marker that has been used in numerous studies investigating 

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ANS pain reactivity. HRV refers to the sequence of time intervals between heart beats.  
Typically this is assessed via electrocardiogram (ECG), whereby the low-frequency (LF) HRV, 
high-frequency (HF) HRV, and low-to-high frequency ratio (LF/HF) are used as indices, 
depending on the research question.  Greater HRV has been associated with better self-regulatory 
capacity (Reynard, Gevirtz, Berlow, Brown, & Boutelle, 2011; Segerstrom & Nes, 2007) and 
decreased sensitivity to experimentally-induced pain (Appelhans & Luecken, 2008). 
In addition to changes seen in response to acute pain, chronic pain can result in long-term 
decreases in HRV. For example, individuals with complex regional pain syndrome (CRPS) have 
been found to have reduced HRV compared with healthy participants, which the authors noted to 
be consistent with “a general autonomic imbalance in cardiovascular regulation” (Terkelsen et 
al., 2012).  In patients with musculoskeletal pain conditions, HRV was correlated with longer 
sick leave (Kristiansen et al., 2011).  Among children and adolescents with chronic pain, HRV is 
significantly lower than healthy youth (Evans et al., 2013).  Moreover, HRV has demonstrated 
sensitivity to change following medical (Jiang et al., 2011; Stein, Dal Lago, Ferreira, Casali, & 
Plentz, 2011) and psychological (Berry et al., 2014; Howorka et al., 2013) interventions.  One 
study examined the relationship between anxiety symptoms and HRV among individuals 
randomly assigned to an ACT or CBT intervention (Davies, Niles, Pittig, Arch, & Craske, 2015); 
all participants had been diagnosed with an anxiety disorder.  HRV was found to predict 
outcomes on an anxiety symptom questionnaire in both groups, such that patients with low 
baseline HRV improved more than those with high baseline HRV.  The authors suggest that 
ACT and CBT may be most effective for people with lower HRV (such as those with chronic 
pain, typically).   
A recent review article (Koenig, Jarczok, Ellis, Hillecke, & Thayer, 2013) summarized the 
research on HRV across pain conditions.  The authors noted that HRV is a physiologically 
grounded, theoretically sound and empirically-supported index that should be considered as an 
outcome measure for interventions targeting pain relief.  Further, the knowledge gained from 
studies of HRV “may have important clinical implications [for] a large variety of health 
conditions” (Koenig, et al., page 312).    
1.2.2.6 Preliminary Data 
In a recent pilot study by our group, twelve adolescents (6 males) with NF1 and PNs and their 
parents completed a 2-day ACT workshop (M age = 16.9 years), with 10 patients and 7 parents 
providing 3-month follow-up data.  Pre-post comparisons showed that patients and parents 
reported that pain interfered significantly less with the adolescents’ daily lives at three months 
(ps<.05).  Additionally, patient-reported pain intensity on a 100-mm visual analogue scale 
significantly declined from baseline to three months (baseline M = 43.0, 3-month M = 29.3; 
p<.05).  Parents reported marginally greater acceptance of their child’s pain (p=.07).  No changes 
were seen in functional ability or mood.  Thus, preliminary findings suggest that an ACT 
intervention has potential as a non-pharmacological method for helping individuals with NF1 
and PNs (Martin et al., manuscript accepted). 
1.2.3 Rationale for the Proposed Study 
Overall, the research on ACT to date indicates that it is as helpful as, or superior to, other 
methodologies (e.g., treatment as usual, traditional CBT, relaxation) for individuals with various 
types of pain.  Thus, it is plausible that it would be helpful to patients with NF1.  However, no 

13 
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Version Date: 02/19/2019 
 
randomized studies have investigated the use of behavioral interventions for pain in the NF1 
population, despite the need for such therapies.  Because pharmacologic treatments do not 
always eliminate painful symptoms (Burns et al., 2011b) and can cause unpleasant side effects 
(Swann, 2001), these options are not always ideal.  Members of our NF1 research team 
conducted a survey of parents with a child with NF1 who was evaluated at the NCI for a clinical 
trial (Martin, Gillespie, Wolters, & Widemann, 2011).  Results indicated that 63% of respondents 
expressed interest in future studies investigating pain.  Establishment of a successful intervention 
targeting chronic pain in NF1 would be a critical step forward in improving the functioning and 
QOL of these patients.   
Since previous studies have suggested that both in-person and internet-delivered ACT 
interventions are efficacious, the proposed study will implement an ACT intervention through 
two, 2-hour in-person sessions and online follow-up with adolescents and young adults with NF1 
and PNs who experience chronic pain.  We chose to use a slightly older age group than our pilot 
study; while the small number of patients in that study prohibited statistical analysis of different 
age groups, our clinical experience suggested that the younger adolescents had more difficulty 
understanding some of the concepts. A randomized study design is warranted based on previous 
literature supporting ACT’s efficacy including our own preliminary data in patients with NF1, 
and because the two-group comparison design will allow us to establish whether patients 
improve more with ACT compared to patients doing their usual strategies to manage pain.  
Moreover, this design will allow for all participants to receive the intervention.  The in-person 
plus internet format was chosen due to the infeasibility of conducting regularly-scheduled 
sessions with patients who live long distances from the NIH and because frequent out-of-home 
sessions are often unrealistic due to time or financial constraints. Finally, it should be mentioned 
that a notable proportion of individuals with NF1 have learning or attention deficits (Hyman et 
al., 2006).  We do not expect this to pose a problem, since ACT and related therapies have 
demonstrated efficacy among individuals with developmental delays and attention problems 
(Robertson, 2011; Zylowska et al., 2008).  While we will screen out prospective participants with 
significant cognitive deficits, we also made a number of modifications to the manual and 
workbook from our pilot study to make the intervention more appropriate for individuals with 
minor cognitive impairments, e.g., ADHD.  For example, we eliminated exercises with more 
abstract metaphors and made several of the assignments more detailed and with more specific 
instructions. In addition, extending the intervention so that we maintain regular contact over 8 
weeks hopefully will enable us to keep less focused individuals on track.   
1.2.4 General Overview  
The proposed study will use a randomized controlled trial design to compare the treatment group 
(Acceptance and Commitment Training; ACT) to a wait-list group (WL) in adolescents and 
young adults ages 16 – 59 years with NF1 and PNs who report chronic pain.  Patients will be 
recruited from Dr. Brigitte Widemann’s NF1 program at the National Cancer Institute, from NF1 
clinics around the country, and via the Children’s Tumor Foundation (CTF) registry.  With all 
patients, we will implement an 8-week in-person and internet-delivered ACT intervention.  All 
participants will complete their Time 1 assessment (ECG and questionnaires) on day 1 at the 
NIH before being randomized.   
Participants assigned to the ACT group will meet with a trained ACT therapist for two in-person 
sessions at the NIH (days 1 and 2). Upon returning home, weekly emails will be sent to patients 

14 
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for 8 weeks, each containing ACT-related information and exercises to complete at home. Video 
chat sessions will be conducted via computer at weeks 2, 4, and 6. These patients will return to 
the NIH at week 8 for their Time 2 assessment (repeat ECG and questionnaires).  They will be 
encouraged to continue using ACT techniques in their daily lives.  They will be sent follow-up 
questionnaires to complete electronically from home six months following completion of the 8-
week intervention (week 32; Time 3).  
Participants assigned to the WL group will return home after completing the Time 1 baseline 
assessment. They will return to the NIH at week 8 to complete Time 2 follow-up measures 
(ECG, questionnaires); these data will serve as the primary comparison with the ACT group and 
will also serve as their baseline assessment for the ACT arm.  These participants will then 
receive the same ACT intervention as described above (two 2-hour in-person sessions, weekly 
emails, biweekly video chat sessions).  They will return to the NIH after the 8-week ACT 
intervention (at about week 16) to repeat follow-up measures, and will then be encouraged to 
continue using ACT techniques in their daily lives.  Six months later (week 40), they will 
complete questionnaires online from home. Thus, because they cross over to the ACT 
intervention after the wait-list period, participants in this group will complete the measures a 
total of 4 times (as opposed to 3 times in the ACT immediate intervention group). 
At the completion of each visit or set of follow-up questionnaires, participants in both groups 
will receive a small amount of money ($30) to thank them for their time. The 8-week data will be 
the primary endpoint and analyses will be conducted to determine changes over time in ACT 
versus WL on the primary outcome measure (pain interference) and various secondary measures 
(outlined below). Forty-one patients per arm will provide 80% power to test the 0 to 8-week 
differences in changes from baseline between the two arms.  
 
 
Days 1-2 
Weeks 
1-8 
Week 8 
Weeks 
8-16 
Week 16 
Week 32 
Week 40 
AC
T 
• Time 1 
evaluation
s 
• In-person 
ACT 
sessions 
• Weekl
y 
emails 
• Video 
chat 
weeks 
2,4,6  
(home) 
• Time 2 
evaluations 
(NIH) 
Continue 
ACT 
practice 
(home) 
 
Time 3 
questionnaire
s 
(home) 
 
WL 
• Time 1 
evaluation
s 
 
 
 
 
• Time 2 
evaluation
s 
• In-person 
ACT 
sessions 
• Weekl
y 
emails 
• Video 
chat 
weeks 
2,4,6  
(home) 
Time 3 
evaluation
s  
(NIH) 
Continue 
ACT practice 
(home) 
Time 4 
questionnaire
s (home) 
 

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2 
ELIGIBILITY ASSESSMENT AND ENROLLMENT  
2.1 
ELIGIBILITY CRITERIA 
2.1.1 Inclusion Criteria for Participant 
2.1.1.1 Patients must be between 16 and 59 years of age at the time of the baseline assessment.  
Because the research on the effectiveness of ACT with younger children is still 
emerging, children 15 and younger will be excluded from the present study.   
2.1.1.2 Diagnosis of NF1 through germline mutation OR clinical diagnosis; for the clinical 
diagnosis of NF1 all study subjects must have two or more diagnostic criteria for NF1 
listed below (NIH Consensus Conference): 
1. Six or more café-au-lait spots (≥0.5 cm in prepubertal subjects or ≥1.5 cm in 
postpubertal subjects) 
2. ≥ 2 neurofibromas or 1 plexiform neurofibroma 
3. Freckling in the axilla or groin 
4. Optic glioma 
5. Two or more Lisch nodules 
6. A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or 
thinning of long bone cortex) 
7. A first-degree relative with NF1 
2.1.1.3 Participants must have documentation of a PN, based on either clinical exam or 
imaging.   
2.1.1.4 Patient must self-report having chronic pain for at least the past 3 months that has 
interfered with their daily functioning, as assessed by the Pain Interference Index (must 
get a mean score of 2.0 or higher, or score a 3 on three or more individual items).   
2.1.1.5 Patients must have regular access to a computer or tablet with internet access. 
2.1.1.6 Ability of subject or Legally Authorized Representative (LAR) to understand and the 
willingness to sign a written informed consent document. 
2.1.1.7 No anticipated major changes in their pain treatment regimen (i.e., new class of pain 
medication starting or change in the class of pain medication) or enrollment on a new 
treatment study presumed to impact pain in the near future. 
2.1.1.8 Subjects must be able to read and comprehend the English language, since the highly 
trained ACT therapists are not fluent enough to conduct the trainings in Spanish or other 
languages.   
 

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2.1.2 Exclusion Criteria for Participant 
2.1.2.1 In the opinion of the PI or an AI, the subject has significant cognitive or emotional 
difficulties that would prevent them from being able to understand and/or participate 
fully in the intervention or the measures.   
2.1.2.2 Subjects who are participating in any other treatment studies, either medical or 
behavioral, specifically for pain management.   
2.1.2.3 Subjects who began a medical intervention for treatment of their disease that has a 
possible impact on pain (including MEK trials) will not be eligible until after one year 
on the medical treatment; at that time, eligibility will be discussed with the PI of the 
medical study to assess the stability of the patient’s pain and whether further pain-
related changes due to the medical treatment are likely. 
2.1.2.4 Inability to travel to the NIH, for example, due to physical limitations, for the in-person 
evaluation(s).   
No groups in regards to gender, race, or ethnicity are being excluded from  participation in the 
trial.    
2.1.3 Recruitment Strategies 
Dr. Widemann has an active clinical trials program for NF1 consisting of both natural history 
and treatment protocols for PNs and MPNSTs, which draws patients from a national referral 
base.  All patients on Dr. Widemann’s study who have reported moderate to severe pain to the 
medical team and are within the study’s age range will be informed about the study unless they 
meet exclusion criteria.  Subjects will be recruited from this referral base, as well as from 
medical centers around the country. We also plan to advertise the study in the Children’s Tumor 
Foundation (CTF) newsletter and website, as well as the CTF Registry.  There are some external 
funds available to assist with travel costs.   
2.2 
SCREENING EVALUATION  
2.2.1 Pain level 
Because it is not feasible to bring patients here from long distances for this protocol and then 
find them ineligible based on questionnaire responses, a screening questionnaire will be 
administered by study staff over the telephone prior to bringing potential subjects to NIH for the 
complete screening evaluation (See Appendix A).   
The screening questionnaire consists of the 6-item Pain Interference Index (PII), which will be 
administered verbally, with the researcher reading the questions to them.  We will ask each 
participant if they prefer to read the questions along with the researcher, in which case we will 
email the questions to them and then resume the call.  To be found eligible, individuals must 
obtain a mean score of 2.0 or higher OR respond with a ‘3’ or higher to three or more items.  
Patients will not be told in advance what PII score criteria they have to meet to be eligible.  In 
addition, they must report that their pain has been present for at least the past three months. They 
also must confirm that they have access to a computer (or tablet or smartphone) with internet 
capability, and that they can read and speak standard English.  Patients who meet these criteria 
and who are interested in participating will be brought to NIH for complete screening at which 
time they will be given a copy of the screening consent that has been reviewed; the consent will 

17 
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then be signed in the clinic.  Patients who are already enrolled on Dr. Widemann’s Natural 
History protocol may be approached in clinic or by phone or email and may be given the 
screening evaluation for the current study at that time if the patient expresses interest in learning 
about the study.   
2.2.2 History and Physical Examination 
Patients who meet the initial phone screening evaluation and who are interested in participating 
will meet with a nurse practitioner or physician for a history and physical examination at the NIH 
Clinical Center.  This will include a complete history (including prior and concurrent 
treatments); physical examination including a neurological examination, documentation of 
performance status, blood pressure, and signs and symptoms of NF1, including a thorough 
history of pain experiences; and pain medications, doses, frequency, etc., and history of cognitive 
diagnoses (ADHD, LD). If the subject is co-enrolled on NCI protocol #08-C-0079 (Natural 
History Study and Longitudinal Assessment of Children, Adolescents, and Adults with 
Neurofibromatosis Type 1), the physical evaluation will not be repeated for this intervention 
study if obtained within 4 weeks of study entry, and the results may be included in the data 
analysis for this study.  If a patient has been evaluated in the past 6 months for the Natural 
History Study, an abbreviated history and physical examination will be conducted, with a 
particular emphasis on recent pain history and pain management.  No other medical screening 
procedures will be done.   
2.3 
REGISTRATION PROCEDURES 
Registration will be a two-part process as patients are screened on this protocol. Authorized staff 
will register an eligible candidate with NCI Central Registration Office (CRO) within 24 hours 
of signing consent.  To initially register a subject after the participant has signed the consent, 
complete the top portion of the registration Eligibility Checklist from the website 
(http://home.ccr.cancer.gov/intra/eligibility/welcome.htm) indicating that the patient is being 
registered for screening and sent via encrypted email to:  NCI Central Registration Office 
ncicentralregistration-l@mail.nih.gov.  Once eligibility is confirmed after completion of 
screening studies, complete the remainder of the form which is the eligibility checklist, 
indicating that the patient is being registered for treatment and email the completed registration 
checklist to the CRO at NCI Central Registration Office ncicentralregistration-l@mail.nih.gov. 
Verification of registration will be forwarded electronically via e-mail to the research team. A 
recorder is available during non-working hours. 
Subjects that do not meet screening criteria should be removed from the study following the 
procedure in section 3.6.   
2.3.1 Treatment Assignment and Randomization/Stratification Procedures 
2.3.1.1 Cohorts 
Number Name 
Description 
1 
Patients 
Patients diagnosed with NF1 through germline mutation 
OR clinical diagnosis 
 

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2.3.1.2 Arms 
Number Name 
Description 
1 
ACT 
ACT intervention 
2 
WL 
Wait List Control Group 
2.3.1.3 Stratifications 
Name 
Distinct Options 
Notes 
Age  
16-24 years 
25-59 years 
 
 
 
 
 
2.3.1.4 Randomization and Arm Assignment 
All patients in cohort 1will be stratified for age and randomized between arms 1 and 2. After 
patients have been on the Wait List Arm for 8 weeks, they will cross over to the ACT arm.     
2.4 
BASELINE EVALUATION   
After signing consent for participation in this study, the following baseline assessments will be 
conducted: 
1. The following questionnaires will be required of all participants (See Section 3.3.1 for 
a complete description of these questionnaires): 
Table of Questionnaires:  
Domain 
Questionnaire Name  
Location 
Completion 
Time* 
Demographics 
Background Information Form 
Appendix B 
2 min 
Pain Interference 
Pain Interference Index 
PROMIS Pain Interference SF – Adult  
PROMIS Pain Interference SF – Pediatric 
Appendix C 
Appendix D 
Appendix E  
2 min 
3 min 
3 min 
NF1 Quality of Life 
PedsQL Neurofibromatosis Type 1 Module  
Appendix F 
5 min 
Pain-related Anxiety 
Pain Anxiety Symptoms Scale-20 (PASS-20) 
Appendix G 
5 min 
Depression 
Center for Epidemiological Studies-Depression 
Scale (CES-D) 
Appendix H  
 
5 min 
Pain Intensity 
Numeric Rating Scale-11 (NRS-11) 
Appendix I 
1 min 

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Pain Acceptance 
Chronic Pain Acceptance Questionnaire 
(CPAQ) 
Appendix J 
5 min 
Psychological 
Inflexibility 
Psychological Inflexibility in Pain Scale (PIPS) 
Appendix K 
3 min 
Recent Life Events  
Life Events Scale (LES) 
Appendix L 
1 min 
Pain Management 
Strategies 
Pain Management Inventory (PMI) 
Appendix M 
Appendix N 
2 min 
ACT adherence 
ACT Inventory** 
Appendix O 
 
Subjective Overall 
Change  
Patient Global Impression of Change scale 
(PGIC)** 
Appendix P 
1 min 
Estimated Reading 
Ability 
Wide Range Achievement Test – Fourth 
Edition (WRAT-4) 
not shown  
2 min 
* Total time required for patients: about 32 – 37 minutes at each time point. 
** The ACT Inventory and PGIC scales are given at follow-up time points only.   
2. Electrocardiogram: a baseline ECG will be performed on all patients.  The ECG will be 
administered in a room in the Pediatric clinic by a trained member of the research 
group (see section 3.3.2).  
3. Imaging (optional): We will examine prior scans of patients’ plexiform tumor if 
available.  We will not perform imaging as part of the current study.  If patients have a 
prior scan taken within one year of beginning this study, we will use this to document 
location of the PN.  If two prior scans are available taken approximately 1 – 2 years 
apart, we will use these to determine if the PN is stable vs. progressive.  We will ask 
patients who have scans from an outside institution to have them mailed to Eva Dombi, 
NCI Pediatric Oncology Branch, 10 Center Drive, Building 10, room 1-5750, 
Bethesda, MD, 20892, or dombie@mail.nih.gov.   
3 
STUDY IMPLEMENTATION 
3.1 
STUDY DESIGN 
3.1.1 Baseline 
On Day 1 after signing consent, participants will be randomized to their group as described 
above (section2.3.1.4). All patients will receive an electrocardiogram (ECG) to assess HRV and 
will be asked to complete a baseline demographic questionnaire and nine baseline 
questionnaires.  The brief demographic questionnaire asks about level of independence, 
occupation and educational history, and history of psychiatric diagnoses.  This form should take 
about 5 minutes to complete. The other nine baseline questionnaires should take 30-35 minutes 
total. The patient will also take a 1- to 2-minute word reading test as an estimate of reading 
ability. Following these baseline procedures, patients will be informed of their randomized group 
assignment.  
Patients who are assigned to the ACT group will meet with their assigned trainer for Session 1, 
typically that same day, and will take part in Session 2 typically the following morning. One 5-

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Abbreviated Title:  ACT Therapy for NF1Related Pain 
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10 minute break will be given during each 2-hour session (see Section 3.2.2 for more 
information on the content of these sessions). At the end of the Day 2 ACT session, patients will 
be given materials to take home so they may continue to practice ACT techniques in their daily 
lives. These include a workbook (see Appendix Q) and an audio CD or MP3 download with 
mindfulness exercises focused on pain. We anticipate that most patients in the ACT group will 
be able to return home on Day 2, depending on travel arrangements.  
Patients assigned to the WL group will return home after the baseline questionnaires and ECG 
are completed. Thus, their total stay at the NIH will be less than 1 day for local patients, and 1 to 
1.5 days for patients traveling long distance.  
Participants in the ACT group will receive weekly emails with a different topic and practice 
exercise each week (Appendix R), and will participate in biweekly, individual video chat 
sessions with their assigned trainer.  This will be the same trainer who conducted their in-person 
sessions, whenever possible (e.g., unless that trainer is out sick for an extended period). These 
sessions will be scheduled to last about 30 minutes each. See Appendix S for the video chat 
manual.   
3.1.2 Follow-up  
Participants in both groups will return to the NIH at the end of the 8-week intervention (not to 
exceed 12 weeks after their initial NIH visit). During this visit, all participants will repeat the 
baseline evaluations: they will complete follow-up questionnaires as listed in section 2.4 and will 
have a second ECG. After those evaluations, the ACT participants will return home with 
instructions to continue using the ACT techniques in their daily lives. The WL participants will 
then receive the 2-session in-person ACT intervention (typically over two days), and then will 
return home to take part in the weekly emails and individual video chat sessions.  
At the end of their 8-week intervention, participants in the WL group will return to the NIH for 
their final in-person visit when they will complete the follow-up questionnaires again and will 
receive their final ECG.  If it is a hardship for patients in the WL group to return for a third visit 
(i.e., for those who live across the country), they will be given the option to complete the 
questionnaires online from home.  Thus, we will have questionnaire data for these patients but 
will forego their second follow-up ECG data.   
Both groups will complete a final set of questionnaires from their home computer, tablet, or 
smartphone about six months (about 24 weeks) after the formal intervention ends.  
3.2 
ACT INTERVENTION  
3.2.1 Therapist Training 
The ACT training sessions (in-person and video chat) will be led by one of four therapists: Dr. 
Staci Martin Peron, who is a licensed psychologist, Dr. Kari Struemph (licensed psychologist), 
Mary Anne Tamula, MA (Psychology Associate), or another Psychology Associate (probably a 
post-doctoral fellow) to be hired for this study; this person will see the majority of patients. All 
sessions led by the Psychology Associates will be supervised by Dr. Martin Peron. Dr. Martin 
Peron and Ms. Tamula have participated in formal ACT training, including attending numerous 
workshops with experts in the field, studying books and articles on ACT techniques, and 
attending a monthly peer consultation group. Dr. Martin Peron has given numerous talks on ACT 

21 
Abbreviated Title:  ACT Therapy for NF1Related Pain 
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for pain management, and has trained and supervised other psychologists, Psychology 
Associates, and psychology graduate students in this area. The other two therapists will 
participate in a local ACT training if one becomes available and will engage in structured 
training and supervision with Dr. Martin Peron. All therapists will complete the Acceptance and 
Commitment Therapy Core Competency Self-Rating Form (Hayes & Strosahl, 2004). To assess 
treatment fidelity, trainers will complete a checklist of techniques and intervention procedures 
after each in-person session (see Appendix T).   
3.2.2 ACT Training Content 
3.2.2.1 In-person ACT sessions 
The in-person ACT sessions will consist of structured techniques focused on helping participants 
cope with their pain more effectively. The sessions will follow a manual that was adapted from 
our previous pilot study for groups of patients with NF-related pain; the format for the current 
study has been adapted for use with individuals. Content also was based on previous manualized 
ACT interventions outlined in books (Dahl, Wilson, Luciano, & Hayes, 2005; Hayes et al., 1999) 
and articles (Masuda et al., 2011; Wicksell, Dahl, Magnusson, & Olsson, 2005; Wicksell et al., 
2007) and used in prior ACT studies with chronic pain patients.   
The ACT manual is presented in Appendix U.  In general, the content of the in-person and video 
chat sessions will be based on the six core therapeutic processes of ACT, each of which are 
interrelated and build upon the others: 
(1) Mindfulness.  Mindfulness is of central importance in ACT. Participants will be taught to 
practice mindfulness exercises to help them be aware of internal and external events as they 
occur. Engaging in mindfulness helps people become more aware of their automatic, 
maladaptive thoughts and be more flexible in their reactions to them.  Basic mindfulness 
exercises, such as focusing on one’s breathing or on particular sights or sounds, will help 
individuals learn to observe and describe these things in a neutral manner. Then the focus of 
mindfulness exercises will be extended to thoughts about the person’s pain.   
(2) Acceptance.  Patients will be encouraged to be willing to experience their pain and the 
thoughts and feelings they have about their pain without judging or trying to change them. They 
will be taught to let go of their struggle against pain as a means of opening themselves up to 
more adaptive ways of living. One’s willingness to experience pain can lead to the creation of a 
more full and vital life, since all the energy once spent avoiding pain can now be focused on 
valued activities and goals.  
(3) Cognitive Defusion.  Defusion refers to the process of separating the words people use from 
their literal meaning. For example, just because a patient has the thought “I can’t stand this pain” 
does not make it true.  Participants will be taught to observe their thoughts without necessarily 
believing them to be true or acting upon them. The therapist accomplishes this by labeling the 
person’s thoughts as only thoughts rather than known facts. If a patient states “I can’t go to the 
football game because my arm hurts” the therapist can reframe that as “You’re having the 
thought that you can’t go to the game” to emphasize that the statement may not be true. This 
gradually helps the people disentangle themselves from their thoughts, and frees them up to 
make choices based on factors other than the immediate thoughts they have about their pain.   

22 
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(4) Self as Context. This aspect of ACT refers to helping participants become more aware of a 
sense of self from which they can observe and accept their thoughts, emotions, and experiences. 
Doing so helps individuals become disentangled from their maladaptive thoughts, since they are 
encouraged to experience them as an observer rather than a participant. This, in turn, helps the 
participant to view his or her struggle with more objectivity and compassion.   
(5) Defining Valued Directions.  Patients will participate in exercises aimed at helping them 
define their core values and then will examine the ways in which their current behaviors are 
interfering with their ability to live their life consistent with their values. The therapists will 
demonstrate how focusing on avoidance of pain means that one is not focusing on valued 
activities. Living in accordance with one’s values and without pain may not be possible.  This is 
an important point for patients to realize.  
(6) Committed Action.  Participants will be asked to define concrete goals that are consistent 
with their core values, and then commit to living in accordance with these goals. Potential 
barriers to reaching their goals will be addressed, with specific focus on how to respond when 
faced with obstacles. Therapists also will focus on how to engage the support of significant 
others (for example, parents, friends, spouses) in one’s pursuit of his or her goals.   
Participants will complete practice exercises on their own in between the two sessions. At the 
end of the second session, patients will be given a workbook to take home that includes a 
summary of the topics discussed during the sessions and exercises for continuing to work on 
ACT techniques at home. In addition, patients will be given an audio CD or MP3 download that 
contains mindfulness meditations geared towards individuals with chronic pain (“Mindfulness 
Meditation for Pain Relief” by Jon Kabat-Zinn).  
3.2.2.2 Emails 
Weekly emails will be sent to each ACT group participant during weeks 1 – 8 (see Appendix 
Q).  These emails will contain a brief summary of a topic relevant to ACT concepts, and an 
exercise or assignment for the participant to complete that week. If the participant emails the 
trainer with a specific question, the trainer will respond as soon as possible (typically within 24 
hours, not including weekends). Any medical questions will be referred to the patient’s medical 
provider. The main content of the emails will be the same across patients, but certain examples in 
the emails may be adapted slightly depending on the patient’s age or individual goals. For 
example, we may discuss a 16-year old patient’s goal of doing well in school, or a 28-year old 
patient’s goal of joining a book club.   
3.2.2.3 Video chat Sessions  
Each individual, 30-minute video chat session will be structured as follows (approximately): 5 
minutes to review the topics from the weekly emails, 15 minutes to introduce a new topic 
(related to previous content), and 10 minutes to discuss any difficulties the patient may be 
experiencing in relation to their pain or the intervention exercises.  The manual for video chat 
sessions is in Appendix S.   

23 
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3.3 
QUESTIONNAIRES  
3.3.1 Patient Questionnaires 
3.3.1.1 Pain Interference  
The Pain Interference Index (PII) is a 6-item questionnaire meant to assess the degree to which 
pain has interfered with daily activities in the past week (Appendix C).  This measure initially 
was developed and validated in Sweden with youth with longstanding idiopathic pain (Wicksell, 
Melin, Lekander, & Olsson, 2009b).  In collaboration with the Swedish researchers, the authors 
of the current study translated the measure to English and also created a parallel parent report 
version (PII-P) and an adult self-report version.  The youth self-report PII has been validated in 
patients ages 6 to 25 years with NF1 and other chronic illnesses (Martin et al., 2014).  For this 
study, this version will be administered to patients ages 16 to 17 and to 18-25 year olds who are 
still in school.  The adult self-report version is parallel to the youth self-report version, with 
minor wording modifications made (changing “school” to “work”).  Initial reliability and validity 
data of the adult self-report version are positive (alpha = .94; manuscript in preparation).  Both 
versions of the scale take about 2 minutes to complete.   
The PROMIS Pain Interference scales will be administered as another assessment of pain 
interference (Appendices C and D); (Amtmann et al., 2010; Varni et al., 2014). The adult 8-item 
short form will be administered to participants ages 18 - 59, and the pediatric 8-item short-form 
will be given to participants ages 16 and 17 years. Both of these scales ask the respondent to 
consider how much pain has interfered with things like sleep, mood, and leisure activities, in the 
past week.  Items are formatted on 0-4 Likert scales.  These measures each take about 2 minutes 
to complete. The PII and the PROMIS pain interference scales are both being given since they 
each have advantages and disadvantages.  Specifically, the PII’s limited items may not capture 
all relevant aspects of pain interference in NF1, but this measure has strong preliminary 
reliability and validity data in this population, which the PROMIS does not yet have.  Moreover, 
giving both measures in conjunction is the current recommendation of the Patient-Reported 
Outcomes (PRO) working group of the Response Evaluation in Neurofibromatosis and 
Schwannomatosis (REiNS) collaboration. 
3.3.1.2 Disease-specific Quality of Life  
The PedsQL NF Module, Adult form is a questionnaire designed to assess various aspects of 
quality of life in individuals with NF1 (Nutakki, Hingtgen, Monahan, Varni, & Swigonski, 2013) 
(Appendix F).  Items on this scale ask the respondent to indicate the extent to which they have 
had problems performing various activities over the past month, using a 0 – 4 Likert scale (0 = 
Never, 4 = Almost Always).  The subscales that will be administered on this study include 
Physical Functioning (7 items) and Daily Activities (12 items).  Mean scores for each subscale 
are linearly transformed to a 0-100 scale, and then can be compared to means and standard 
deviations of a normative group of patients with NF1.  These two subscales should take less than 
five minutes to complete.   
3.3.1.3 Pain-related Anxiety 
The Pain Anxiety Assessment Scale – 20 (PASS-20) is a 20-item measure developed to assess 
pain-related anxiety in medical patients (McCracken & Dhingra, 2002; see Appendix G).  Items 
are answered on a 6-point Likert scale with anchors of “never” and “always.”  Responses provide 

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a total score and scores on four subscales: Cognitive Anxiety, Pain-related Fear, Escape and 
Avoidance, and Physiological Anxiety.  The PASS-20 is reliable (Cronbach’s alpha = .81) and 
valid (L. M. McCracken & Dhingra, 2002; Roelofs et al., 2004).  The measure takes about 5 
minutes to complete.  
3.3.1.4 Depression  
The Center for Epidemiological Studies – Depression scale (CES-D) (Radloff, 1977) is a 20-item 
measure originally developed for use with individuals 18 years and older, and has since been 
validated with adolescents as young as 12 years (Garrison, Addy, Jackson, McKeown, & Waller, 
1991). Respondents are asked to rate how frequently in the past week they have experienced a 
list of symptoms, such as feeling depressed, enjoying life, having problems sleeping, and feeling 
liked by people.  Items are scored on a 0 (rare or none of the time) to 3 (most of all of the time) 
format.  Individual responses yield scores on four subscales: depressive affect, positive affect, 
somatic activity, and interpersonal.  A total depression score is obtained that can range from 0 to 
60, with higher scores representing worse depressive symptoms.  This tool has been shown to be 
valid and reliable in clinical populations (Orme, Reis, & Herz, 1986) and with medical patients, 
including those with chronic pain (Hann, Winter, & Jacobsen, 1999; Turk & Okifuji, 1994).  
This questionnaire takes approximately 5 minutes to complete (See Appendix H).   
3.3.1.5 Pain Intensity   
The Numeric Rating Scale – 11 (NRS-11) consists of two questions that assess pain intensity.  
The items are formatted along a horizontal line with from 0 (no pain) to 10 (worst pain 
imaginable) spaced equidistant along the line (Appendix I).  Respondents circle the one number 
that best represents their pain currently, and in the past week.  This measure is widely used and is 
recommended for use in clinical trials for patients with chronic pain, including NF1 (Wolters et 
al 2013; Gilron & Jensen, 2011).  It takes less than one minute to complete.  
3.3.1.6 Coping with Pain 
The Chronic Pain Acceptance Questionnaire (CPAQ; (L. M. McCracken et al., 2004) was 
designed to assess one’s ability to accept his or her pain, and is typically used with patients ages 
18 years and older.   Respondents answer 20 questions on a 0 (never true) to 6 (always true) 
rating scale, with higher scores indicating higher levels of acceptance.  Scores are obtained on 
two subscales (Activities Engagement and Pain Willingness) and an Acceptance Total scale. 
Reliability and validity, and sensitivity to change have been demonstrated (Huggins et al., 2012; 
Vowles & McCracken, 2008).  The CPAQ takes approximately 5 minutes to complete (See 
Appendix J).  
3.3.1.7 Psychological Inflexibility  
The Psychological Inflexibility in Pain Scale (PIPS) is a 12-item measure that assesses the extent 
to which an individual engages in avoidance of activities because of their pain (experiential 
avoidance) and inflexible thinking about their pain (cognitive fusion) (Wicksell, Lekander, 
Sorjonen, & Olsson, 2010); Appendix K). The measure asks respondents to rate how true the 
statements are for them currently, on a Likert scale of 1 (never true) to 7 (always true).  Eight of 
the items are summed to yield a score on the Avoidance subscale, and four of the items are 
summed for the Fusion subscale.  A total score also is obtained by summing all 12 items. The 
PIPS has been found to have good internal consistency and strong correlations with criterion 

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variables such as pain intensity, use of pain medication, and other measures of activity avoidance 
(Trompetter et al., 2014; Wicksell et al., 2010).  The form takes about 3 minutes to complete.   
3.3.1.8 Recent Life Events 
Because stressful life events may impact pain and coping, we will administer the Life Events 
Scale (LES), a measure designed to assess significant events that have occurred in the patient’s 
life in the past six months (Appendix L).  The patient is asked to indicate which events have 
occurred in their life from a list of 43 potential events.  This scale has shown reliability and 
validity (Elliott-Desorbo, Martin, & Wolters, 2009). 
3.3.1.9 Pain Management  
The Pain Management Inventory (PMI) was developed by our group to assess what techniques 
patients use to manage their pain, including pharmacological and non-pharmacological 
treatments. Specifically, respondents are asked what pain medications they have taken in the past 
month and how frequently. Another question asks about any other (non-pharmacological) 
techniques in which participants have engaged (e.g., relaxation, massage) for coping with pain in 
the past month. At the 6-month time point, there is an additional question on this form that asks 
whether the patient has had surgery for their NF1 in the past six months.  This measure takes 
about 2 minutes to complete (see Appendix M and Appendix N).   
3.3.1.10 Adherence to ACT Intervention 
The ACT Inventory was developed by our group to assess the frequency with which participants 
have engaged in ACT strategies in the past month.  Six items ask how much participants have 
used mindfulness, defusion, and other ACT techniques taught during the intervention to help 
them cope with pain in their daily lives.  One item asks how much the person liked participating 
in the study.  This will be given at follow-up time points only, and takes about 2 minutes to 
complete (see Appendix O).    
3.3.1.11 Subjective Change Rating 
The Patient Global Impression of Change (PGIC) scale is one item used to assess the patient’s 
overall impression of their level of pain interference at the end of the study compared to baseline 
(see Appendix P).  Versions of this scale have been used in studies of various pain populations 
(Arnold, Zlateva, Sadosky, Emir, & Whalen, 2011; Mohammad et al., 2014). Also, this measure 
has been recommended by the Initiative on Methods, Measurement, and Pain Assessment in 
Clinical Trials (IMMPACT) for use in clinical trials involving chronic pain (Dworkin et al., 
2005).  It takes less than one minute to complete.   
3.3.2 ECG procedures 
An ECG will be given to assess heart rate variability.  In accordance with recommendations from 
the European Society of Cardiology and North American Society of Pacing and 
Electrophysiology Task Force ("Heart rate variability. Standards of measurement, physiological 
interpretation, and clinical use. Task Force of the European Society of Cardiology and the North 
American Society of Pacing and Electrophysiology," 1996), the reading will occur for 5 minutes 
while the patient is lying down (for ease of electrode placement). We will obtain several 
measurements, including the standard deviation of the average NN (normal-to-normal) interval 
(SDANN) and the square root of the mean squared differences of successive NN intervals 

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(RMSSD).  At baseline and follow-up visits, we will attempt to take measurements at 
approximately the same time of the day, since HRV can fluctuate throughout the day.  Since the 
Wait-List group will essentially have two baseline assessments (one at enrollment and one before 
they start the ACT intervention), patients in this group will have three ECGs while the 
Immediate Intervention group will get a total of two ECGs.  A standard “ECG Procedures” form 
will be used to capture any abnormalities in administration, such as if a patient coughs or talks 
during the administration.  This form also will record whether the patient had any caffeine that 
day, and approximately how much, since caffeine can impact heart rate.   
3.3.3 Word Reading test 
The Word Reading subtest from the Wide Range Achievement Test 4 will be administered to 
patients in order to estimate their reading ability. This task is also a widely recognized proxy of 
cognitive functioning.  This will allow us to control for this variable statistically, if there are any 
systematic differences related to how people with different reading skills (and proximal cognitive 
abilities) respond to the intervention, which is conceptually diverse and involves reading weekly 
emails.  For this task, patients are asked to read a list of words aloud to the examiner.  The Word 
Reading subtest takes about one to two minutes to complete. 
 
 

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3.4 
STUDY CALENDAR 
Procedure 
Screeni
ng 
 
Baseline 
Week 8 
Week16  
Week 
32 
 
Week 
40 
History and Physical 
Exam 
X 
 
 
 
 
 
Pain Interference Index 
X 
 
 
 
 
 
Questionnaires* 
 
 
 
 
 
 
• ACT 
 
X 
X 
 
X 
 
• WL 
 
X 
X 
X 
 
X 
Word Reading 
• ACT 
• WL 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
Electrocardiogram 
 
 
 
 
 
 
• ACT 
 
X 
X 
 
 
 
• WL 
 
X 
X 
X 
 
 
Intervention 
 
 
 
 
 
 
• ACT 
 
X 
 
 
 
 
• WL 
 
 
X 
 
 
 
Adverse Events 
 
X 
X 
X 
X 
X 
*as listed in Section 3.3.1. 
3.5 
COMPENSATION 
To thank participants for their time during participation, participants will receive $30 for 
each visit. Funds will be distributed in accordance with the Clinical Center’s Research 
Volunteer system, such that participants can have the money directly deposited to a bank 
account or have a check mailed to them.   
3.6 
CRITERIA FOR REMOVAL FROM PROTOCOL 
Participants will be removed from this study for any of the following: 
• Screen failure 
• Completion of protocol requirements 
• Participant requests to be withdrawn from study 
• Patient begins a new treatment that is likely to impact pain (e.g., MEK inhibitor) 
• Patient reports a significant increase in pain that necessitates a new pain treatment or a 
medical procedure (i.e., surgery) that would notably impact pain levels. (These patients 
could re-enroll at a later date, if they again met criteria for this study and had not received 
the full in-person ACT intervention).   
• Lost to follow up 
• Investigator feels that it is in the best interest of the participant to withdraw from 
participation. 

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Note: all minors, who have signed the standard consent or assent, will be kept on study and 
followed until the age of 18 to allow consent. 
3.6.1 Off-Study Procedure 
Authorized staff will notify Central Registration Office (CRO) when a subject is taken off-study. 
A Participant Status Updates Form from the website 
(http://home.ccr.cancer.gov/intra/eligibility/welcome.htm)  main page must be completed and 
sent via encrypted email to:  NCI Central Registration Office ncicentralregistration-
l@mail.nih.gov. 
4 
DATA COLLECTION AND EVALUATION  
4.1 
DATA COLLECTION 
All questionnaires will be administered via computer or mobile tablet devices.  The PI will be 
responsible for overseeing entry of data into an in-house password protected electronic system 
and ensuring data accuracy, consistency and timeliness. The principal investigator, associate 
investigators/research nurses and/or a contracted data manager will assist with the data 
management efforts.  All data obtained during the conduct of the protocol will be kept in secure 
network drives or in approved alternative sites that comply with NIH security standards. Primary 
and final analyzed data will have identifiers so that research data can be attributed to an 
individual human subject participant.  
Adverse events occurring as a result of treatment for the underlying condition or medical 
treatment for pain will NOT be recorded or reported on this study. 
End of study procedures: Data will be stored according to HHS, FDA regulations, and NIH 
Intramural Records Retention Schedule as applicable.  
Loss or destruction of data: Should we become aware that a major breach in our plan to protect 
subject confidentiality and trial data has occurred, the IRB will be notified. 
5 
SAFETY REPORTING REQUIREMENTS/DATA AND SAFETY MONITORING 
PLAN 
5.1 
DEFINITIONS 
5.1.1 Adverse Event 
An adverse event is defined as any reaction, side effect, or untoward event that occurs during the 
course of the clinical trial associated with the intervention, whether or not the event is considered 
related to the treatment or clinically significant.   
For this study, AEs will primarily include events reported by the patient. Since this is a 
behavioral intervention and no drug therapy will be administered on this study, physical signs 
and symptoms as adverse events are not anticipated. A new illness, symptom, sign or clinically 
significant laboratory abnormality or worsening of a pre-existing condition or abnormality that 
occurs during the NIH visit which is not directly related to the participation in the baseline 
treatment sessions or completing the baseline questionnaires will not be reported on this study, 

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but will be referred to the medical physician responsible for the participant’s care. All AEs must 
be recorded on the AE case report form unless otherwise noted above in Section 4.1.  
5.1.2 Suspected adverse reaction 
Suspected adverse reaction means any adverse event for which there is a reasonable possibility 
that study participation caused the adverse event. For the purposes of safety reporting, 
‘reasonable possibility’ means there is evidence to suggest a causal relationship between study 
participation and the adverse event. A suspected adverse reaction implies a lesser degree of 
certainty about causality than adverse reaction, which means any adverse event caused by study 
participation. 
5.1.3 Unexpected adverse reaction 
An adverse event or suspected adverse reaction is considered “unexpected” if it is not listed in 
the protocol or is not listed at the specificity or severity that has been observed. "Unexpected”, 
also refers to adverse events or suspected adverse reactions that are mentioned in the protocol or 
consent but not at the severity or frequency indicated.   
5.1.4 Serious  
An Unanticipated Problem or Protocol Deviation is serious if it meets the definition of a Serious 
Adverse Event or if it compromises the safety, welfare or rights of subjects or others. 
5.1.5 Serious Adverse Event 
An adverse event or suspected adverse reaction is considered serious if in the view of the 
investigator or the sponsor, it results in any of the following: 
• Death, 
• A life-threatening adverse experience 
• Inpatient hospitalization or prolongation of existing hospitalization 
• Persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
• A congenital anomaly/birth defect. 
• Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered a serious adverse drug experience when, based upon 
appropriate medical judgment, they may jeopardize the patient or subject and may require 
medical or surgical intervention to prevent one of the outcomes listed in this definition. 
5.1.6 Disability 
A substantial disruption of a person’s ability to conduct normal life functions. 
5.1.7 Protocol Deviation (NIH Definition) 
Any change, divergence, or departure from the IRB-approved research protocol. 
5.1.8 Non-compliance (NIH Definition) 
The failure to comply with applicable NIH Human Research Protections Program (HRPP) 
policies, IRB requirements, or regulatory requirements for the protection of human research 
subjects. 

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5.1.9 Unanticipated Problem 
Any incident, experience, or outcome that: 
• Is unexpected in terms of nature, severity, or frequency in relation to  
(a) the research risks that are described in the IRB-approved research protocol and 
informed consent document; Investigator’s Brochure or other study documents, and 
(b) the characteristics of the subject population being studied; AND 
• Is related or possibly related to participation in the research; AND 
• Suggests that the research places subjects or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or 
recognized. 
5.2 
NIH INTRAMURAL IRB AND CLINICAL DIRECTOR REPORTING 
5.2.1 NIH Intramural IRB and NCI CD Expedited Reporting of Adverse Events, Unanticipated 
Problems, and Deaths 
The Protocol PI will report in the NIH Problem Form to the NIH Intramural IRB and NCI 
Clinical Director: 
• All deaths, except deaths due to progressive disease  
• All Protocol Deviations 
• All Unanticipated Problems 
• All non-compliance 
Reports must be received within 7 days of PI awareness via iRIS. 
5.2.2 NIH Intramural IRB Requirements for PI Reporting of Adverse Events at Continuing 
Review 
The protocol PI will report to the NIH Intramural IRB:  
1. A summary of all protocol deviations in a tabular format to include the date the deviation 
occurred, a brief description of the deviation and any corrective action. 
2. A summary of any instances of non-compliance 
3. A tabular summary of the following adverse events: 
• All Grade 2 unexpected events that are possibly, probably or definitely related to the 
research;  
• All Grade 3 and 4 events that are possibly, probably or definitely related to the 
research;  
• All Grade 5 events regardless of attribution;  
• All Serious Events regardless of attribution.  
NOTE: Grade 1 events are not required to be reported.  

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5.3 
DATA AND SAFETY MONITORING PLAN 
5.3.1 Principal Investigator/Research Team  
The clinical research team will meet on a regular basis to ensure that treatment implementation 
and follow up data collection are organized and completed in a timely fashion. The principal 
investigator or AI will review all data within one week of submission.  Adverse events will be 
reported as required above.  Any safety concerns, new information that might affect either the 
ethical and or scientific conduct of the trial, or protocol deviations will be immediately reported 
to the NIH Intramural IRB using iRIS.  
The principal investigator will review adverse event and response data on each patient to ensure 
safety and data accuracy.  The principal investigator will personally conduct or supervise the 
investigation and provide appropriate delegation of responsibilities to other members of the 
research staff.  
6 
STATISTICAL SECTION   
6.1 
PRIMARY AND SECONDARY OUTCOMES 
The primary objective of the trial is to compare pain interference mean score changes from 
baseline to 8 weeks between the ACT intervention group and the WL group.  In the pilot study 
conducted by our group, mean scores on PII self-report went from 2.1 (1.0) to 1.5 (1.1), with 
paired differences having a mean change of -0.68 and SD=1.3.  Based on this preliminary 
estimated change for the ACT group, and an assumption of no change in the WL group and a 
corresponding, reduced SD = 0.8, forty-one patients will be needed per group to have 80% power 
to detect a difference in change score between the two arms of -0.68, using a t-test with 
significance level of .05 (two-sided). Secondary analyses will be performed to compare between-
group changes from baseline to 8 weeks and from baseline to 32 weeks on the following 
endpoints: disease-related quality of life, pain severity, pain-related anxiety, and depression.  
Given the wide age range of the study, we will stratify analyses by age (16 – 24 years; 25 – 59 
years).  Descriptive statistics will be computed on the primary and secondary outcome measures 
(means, standard deviations, etc.).  If there are significant differences between the groups at 
baseline (for example, with respect to gender or number of patients on pain medication), analysis 
of covariance (ANCOVA) may be used to control for these differences statistically during 
follow-up analyses (treating baseline as a covariate).  We also will assess for differences between 
the group randomized to ACT and the WL group on primary and secondary outcomes, 
particularly comparing primary results from 0 to 8 weeks for ACT vs. 8 to 16 weeks for WL 
(receiving ACT starting at 8 weeks); if the results are similar (for example, p>0.30 
approximately), we will combine these groups to report the overall effect of ACT for 8 weeks, 
and also examine changes from baseline to 8 weeks and 8 to 16 weeks using an appropriate 
statistical test. Finally, based on a priori hypotheses and prior literature, we will test for indirect 
effects of acceptance and psychological flexibility with simple mediation model analyses.  We 
will generate 5,000 bootstrapped samples using Preacher and Hayes’ (Preacher & Hayes, 2004) 
INDIRECT macro.  Post-treatment scores will be used for these analyses.  Additionally, we will 
examine whether a previous cognitive diagnosis (ADHD or learning disability), reading ability, 
disease characteristics (stable vs. progressive disease, location of plexiform neurofibroma), or 
recent life events, relate to changes over time in the primary outcome with an ANOVA, and if so 

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we may control for these variables in other analyses with an ANCOVA.  Finally, we will 
compare the psychometric properties of the PII and PROMIS Pain Interference Scale by 
examining internal consistency in the patient sample (computed by Pearson correlations) and the 
response to change (as described in the primary objective analysis above). Data will be entered 
into a secure database, then analyzed using SAS statistical software.  
6.2 
SUBJECT ACCRUAL 
We will attempt to enroll up to 41 patients per group.  Patients who complete the WL arm of the 
study will cross-over to the ACT arm.  To provide for patients who enroll but then drop out 
before completing all follow-up measures, we will attempt to enroll up to 90 patients total. As of 
January 2015, approximately 70 of the patients enrolled on the NF1 Natural History study (08-C-
0079) are within the eligible age range of the study, and are not on a MEK inhibitor trial (or 
planning to start one in the next six months).  In addition, about 300 individuals are signed up on 
the CTF registry and are within the study’s age range and have a PN.  We will email these 
individuals as another recruitment source (see Appendices S & T for emails). Additionally, we 
will send email fliers to other NF clinics in the U.S. that see patients within this study’s age 
range (e.g., Johns Hopkins, University of Chicago, Massachusetts General Hospital, etc.).  The 
flier is in Appendix W.  If 5 – 6 patients per month are entered onto this intervention study, data 
collection could be completed within 30 months.  Given that external funding will provide a full-
term postdoctoral fellow who will help with scheduling and will conduct the majority of the 
ACT treatment sessions, this is presumed to be a reasonable goal.   
7 
HUMAN SUBJECTS PROTECTIONS  
7.1 
RATIONALE FOR SUBJECT SELECTION 
Neurofibromatosis type 1 is a genetic disorder with a worldwide incidence of 1:3500 individuals. 
No groups, in regards to gender, race or ethnicity, are being excluded from participation in the 
trial. Because the research on the effectiveness of ACT with younger adolescents is still 
emerging, children 15 and younger will be excluded from the present study. 
7.2 
PARTICIPATION OF CHILDREN 
Children 16-17 years of age will be entered onto this research trial. Children will be evaluated by 
clinicians trained in pediatrics, and will be cared for in the pediatric clinic or outpatient setting.  
Some of the participants will be co-enrolled on Dr. Brigitte Widemann’s NCI protocol 08-C-
0079 (Natural History Study and Longitudinal Assessment of Children, Adolescents, and Adults 
with Neurofibromatosis Type 1), where the physical needs of participants will be addressed.  If 
patients require hospital admission, they will be cared for on the pediatric unit of the CRC by the 
POB staff or on the adult unit of the CRC, depending on age.   
7.3 
PARTICIPATION OF SUBJECTS UNABLE TO GIVE CONSENT 
Subjects unable to give consent are excluded from enrolling in the protocol. Should the subject 
become decisionally impaired during participation he/she will be removed from study as they 
will no longer be capable of completing the research interventions. 

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7.4 
EVALUATION OF BENEFITS AND RISKS/DISCOMFORTS. 
As this is a behavioral intervention study, no medical treatments will be administered and 
therefore the risks are considered minimal. The completion of questionnaires requires a 
maximum of 35 minutes at baseline and follow-up time points. Although we do not anticipate 
this, one potential risk of participation is significantly increased levels of anxiety related to the 
sessions, such as discussing the impact of pain on quality of life and the time involved in 
completing exercises at home.  The study’s PI (Dr. Martin Peron) and the other trainers will be 
closely monitoring patients for any such distress.  They are prepared to address any signs or 
symptoms of anxiety or emotional distress that occur throughout the sessions.  Also, if patients 
endorse a significant level of depression on the CES-D, defined as a raw score of 27 or higher 
(Geisser, Roth, & Robinson, 1997), Dr. Martin Peron or another trainer under Dr. Martin Peron’s 
supervision will be available to respond (this form will be checked within 24 hours of 
completion and before the patient leaves the NIH). Responses could include discussing these 
concerns with the participant, referral for a psychiatry consult while at the NIH, and/or providing 
referrals for therapeutic services in the participant’s local area beyond the scope of the 
intervention.  Any services provided at the NIH in response to an urgent psychological problem 
that occurs during the workshop will be at no cost to the participant.  While this is not anticipated 
to be necessary, if it is judged to be in the best interest of the participant to stop the study 
sessions prematurely, this will be done.  Another small risk is involved with electrocardiogram, 
in that the person may develop a mild rash where the electrodes were attached.  This is rare, and 
the rash often goes away without treatment.   
The research on ACT to date indicates that it is at least as helpful as standard care and other 
methodologies (e.g., traditional cognitive-behavioral therapy, relaxation training) for individuals 
with various types of pain, and more effective than treatment as usual or inactive control groups. 
Thus, there is the potential for direct benefit to participants.  
For participants who are 16-17, this research does not involve greater than minimal risk, and 
participants in this age group will be provided with the opportunity to assent to participate.  
Hence this study meets the requirements of 45 CFR 46.404 in that it does not involve greater 
than minimal risk, but there may also be the potential for direct benefit from participation.  
7.5 
CONSENT AND ASSENT PROCESS AND DOCUMENTATION 
The questionnaires and training sessions involved in this study and the attendant risks, 
discomforts and benefits of these processes, will be carefully explained to the patient and the 
patient’s parents or guardian if he/she is a minor.  All family members who are present will be 
given the opportunity to ask questions.  Patients (and parents in the case of minors) will be given 
the opportunity to discuss their decision privately for as long as they request, either in the clinic 
room or in a location of their choice.  A signed informed consent document will be obtained 
prior to entry onto the study and completion of baseline questionnaires. Written consent or assent 
for children 16-17 years of age for participation in this study will be obtained by the principal 
investigator or an associate investigator.  
For adolescent participants (ages 16-17 years), the investigators are requesting a waiver from the 
IRB to allow only one parent to sign the informed consent for protocol entry.  Because many 
patients must travel to the NIH from long distances at substantial expense, requiring both parents 
to be present for the consent process could be a financial hardship for many families.  The PI or 

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an associate investigator will obtain consent in all cases. When guardianship status of the child is 
uncertain, documentation of custody status must be obtained. 
In situations where there is joint custody of a child, both parents must sign consent. If only one 
parent can be present at NIH, the other parent’s consent can be obtained by telephone via the 
procedure described in section 7.5.3. 
Where deemed appropriate by the clinician and the adolescent’s parent(s) or guardian, the 
adolescent will also be included in all discussions about the trial and age-appropriate language 
will be used to describe the procedures and tests involved in this study, along with the risks, 
discomforts and benefits of participation. Adolescents under the age of 18, but who are age >16 
or older will be asked to sign an age appropriate assent form. The consent/assent process will be 
documented in the adolescent’s medical record, including the assessment of the adolescent’s 
ability to provide assent (verbal versus written) as applicable.   
7.5.1 Request for waiver of consent for screening evaluation 
Although consent will be obtained prior to enrollment on this study, a waiver is requested for 
obtaining informed consent to send recruitment e-mails and to conduct initial screening questions 
over the phone.  According to OHRP, “In order to permit investigators to obtain and record 
identifiable private information for the purposes of identifying potential subjects, OHRP expects 
that IRBs routinely will waive the requirement for informed consent for such activities. In 
assessing the level of risk to determine whether a waiver of informed consent or parental 
permission is permissible for the identification of potential subjects, the IRB need only consider 
the risk of investigators accessing the subjects’ identifiable private information, not the risks of 
the research in toto. (From Frequently asked questions from OHRP: 
http://answers.hhs.gov/ohrp/categories/1566). 
7.5.2 Consent for minors when they reach the age of majority  
When a pediatric subject reaches age 18, continued participation (including ongoing interactions 
with the subject or continued analysis of identifiable data) will require consenting of the now 
adult with the standard protocol consent document to ensure legally effective informed consent 
has been obtained. Given the length of time that has transpired for some of the subjects since 
their last visit for this study, we request waiver of informed consent for those individuals who 
have completed their participation in the research study. 
Requirements for Waiver of Consent consistent with 45 CFR 46.116 (d): 
(1) The research involves no more than minimal risk to the subjects. 
a. Analysis of samples and data from this study involves no additional risks to 
subjects. 
(2) The waiver or alteration will not adversely affect the rights and welfare of the 
subjects. 
a. Retention of these samples or data does not affect the welfare of subjects.  
(3) The research could not practicably be carried out without the waiver or alteration. 
a. Considering the length of time between a minor’s enrollment and their age of 
majority, it is possible that more than a few subjects may be lost to follow 

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up.  A significant reduction in the number of samples analyzed could impact 
the quality of the research.  
(4) Whenever appropriate, the subjects will be provided with additional pertinent 
information after participation. 
a. We only plan to request a waiver of consent for those subjects who have been 
lost to follow-up or who, prior to the approval of Amendment D, have been 
taken off study prior to reaching the age of majority. 
7.5.3 Telephone consent 
The informed consent document will be sent to the subject.  An explanation of the study will be 
provided over the telephone after the subject has had the opportunity to read the consent form.  
The subject will sign and date the informed consent. 
The original informed consent document will be sent back to the consenting investigator who 
will sign and date the consent form with the date the consent was obtained via telephone.   
A fully executed copy will be returned via mail for the subject’s records. 
The informed consent process will be documented on a progress note by the consenting 
investigator. 
7.5.4 Telephone assent 
The informed consent and assent documents will be sent to the parents/guardian and child. An 
explanation of the study will be provided over the telephone after the parents/guardian and child 
have had the opportunity to read the documents.  Age-appropriate language will be used to 
discuss the study with the child.  The parents/guardian will sign and date the informed consent, 
including the line for verbal assent of a child if appropriate. If an assent form is used (see above 
for when an assent form will be used), the child will sign and date that form. 
The original signed informed consent and assent documents will be sent back to the consenting 
investigator who will sign and date the consent form with the date the consent was obtained via 
telephone.   
A fully executed copy will be returned via mail to the subject. 
The informed consent and assent process will be documented on a progress note by the 
consenting investigator. 
 
 

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8 
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Turk, D. C., & Okifuji, A. (1994). Detecting depression in chronic pain patients: adequacy of 
self-reports. Behav Res Ther, 32(1), 9-16.  
Twohig, M. P., Hayes, S. C., & Masuda, A. (2006). Increasing willingness to experience 
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10.1016/j.beth.2005.02.001 
Varni, J. W., Magnus, B., Stucky, B. D., Liu, Y., Quinn, H., Thissen, D., . . . DeWalt, D. A. 
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1233-1243. doi: 10.1007/s11136-013-0544-0 
Veehof, M. M., Oskam, M. J., Schreurs, K. M. G., & Bohlmeijer, E. T. (2011). Acceptance-
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Vowles, K.E., & McCracken, L. M. (2008). Acceptance and values-based action in chronic pain: 
a study of treatment effectiveness and process. Journal of Consulting and Clinical 
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10.1007/s11060-014-1522-2 
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10.1177/1087054707308502 
 
 
 
 

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9 
APPENDICES 
9.1 
APPENDIX A: SCREENING PHONE CALLS TO DETERMINE ELIGIBILITY 
I) Introduction 
• Hi, this is ______ calling from the NIH.  I’m calling to tell you about a study we are 
conducting for people with NF1 and plexiform tumors who have chronic pain.  Do you have 
a few minutes now to hear about the study?   
II) ACT 
• The study is investigating something called Acceptance and Commitment Training, or ACT.  
ACT is a type of therapy that focuses on things like values and living in the present moment.  
It has been found to be effective in helping people with other medical conditions cope with 
their pain, and we have a small amount of data in adolescents with NF1 that suggests it is 
helpful in reducing the amount that pain interferes with the person’s life. The study would 
involve coming to the NIH two or three times over the course of a few months, and will also 
involve doing some of techniques in your day-to-day life at home.  We are hoping that the 
ACT training will help people cope with their pain so that it has less impact on their life, and 
that it will improve people’s quality of life.  To thank participants for their time, we will be 
providing $30 each time you complete a set of baseline or follow-up questionnaires.  You 
would get the money by check or direct deposit.  Do you think you might be interested in 
hearing more about the study?   
• If no: Thank you for your time.   
• If yes: Okay, before I go into too much detail, let me ask you a few questions to see if you’re 
eligible.  This should take less than five minutes.  If you want, I can email you these 
questions to read along with me.  Would you prefer that?  [If yes, email the questions and 
resume the call when they receive it.] 
III) Screening 
I’m going to ask you six questions about your pain.  On a scale of 0 to 6, where 0 means not at 
all and 6 means completely, please think about the following questions: 
 
Has your pain: 
Not at 
all 
 
 
Some 
 
 
Comp-
letely 
1. 
made it difficult for you to do work (in or 
outside the home)? 
0 
1 
2 
3 
4 
5 
6 
2. 
made it difficult for you to do activities 
outside of work (leisure activities)? 
0 
1 
2 
3 
4 
5 
6 
3. 
made it difficult for you to spend time with 
friends and family members? 
0 
1 
2 
3 
4 
5 
6 

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4. 
affected your mood? 
0 
1 
2 
3 
4 
5 
6 
5. 
affected your ability to do physical activities 
(like run, walk up stairs, play sports, do 
chores)?  
0 
1 
2 
3 
4 
5 
6 
6. 
affected your sleep? 
0 
1 
2 
3 
4 
5 
6 
 
Three or more items answered as “some”?        
Yes 
 
No 
OR 
Mean score of 2.0 or above?    
 
 
Yes 
 
No 
 
Okay, now just four more questions:  
[Circle the patient’s responses to the following questions:] 
 
• 
How long have you had this pain?  (> 3 months?) 
   Yes     No 
• 
Do you have access to a computer, tablet, or smartphone with internet 
capability? 
   Yes     No 
• 
Do you have any problems reading English? 
   Yes     No 
• 
Are you planning to start any other new studies for treating your pain or 
your tumors?   
   Yes     No 
 
• If not eligible: I’m sorry, but you are not eligible for the study because ______________.  
However, if you are interested, I can provide you with some online resources about ACT 
that you can read on your own.   
• If eligible: Okay, these initial screening questions suggest that you are eligible for the 
study.  Now I’ll tell you a little more about it to see if you are interested.    
IV) Procedures 
• People who participate in this study will come to the NIH two to three times. The first time, 
you would come for about two days. During this visit:  
o Randomization – we will randomly assign people to the immediate intervention 
group or to the delayed intervention group.   
o All patients will:  
▪ Fill out questionnaires asking about pain, quality of life, emotional well-
being 
▪ Get an electrocardiogram, or EKG – painless, to read heart rate 
o Immediate Intervention group –  

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▪ This group will stay and do four hours of ACT Training (two 2-hour 
sessions) with a psychologist or psychology associate. 
o Delayed/Wait-list group –  
▪ Go home and do nothing different for two months, return for intervention 
after 8 weeks.  During this time, if you were to start a new pain treatment 
or treatment study that might impact your level of pain, we would have to 
remove you from this study.   
V) ACT Training 
• You will learn some techniques that have been found effective for helping people deal 
with pain; ACT does not get rid of pain, it helps people change their relationship with 
their pain.  In other words, instead of trying to fight your pain, we can talk about ways of 
living with your pain while focusing your energy on things that are most important to 
you.  In this way, we try to help you have the best quality of life you can have, even 
while you have pain.   
• You will continue to practice the ACT techniques at home: 
o Weekly emails – on an ACT-related topic with an assignment, something to 
practice during that week 
o Biweekly video chat sessions with a trainer to check on progress, continue to 
work on ACT techniques 
VI) Follow-up 
• All patients will return to the NIH after they complete the 8-week intervention: 
o Repeat questionnaires and EKG 
• Final follow-up 6 months later from home 
o Repeat questionnaires from home computer 
• To thank you for your time, we will be providing participants with a small amount of 
money each time they complete the follow-up questionnaires.  We will also cover the 
costs of travel and some meals during your visits.   
 
VII) Patient Interested? 
Does this sound like something you would be interested in?   
If no: Thank you for your time. 
If yes: Okay, great!  Let’s try to find some possible dates when you could come for your first 
visit (ask about any upcoming surgeries that we may need to schedule around).   
If eligible and interested, find possible dates for first visit: 
 
 
 

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9.2 
APPENDIX B: ADULT BACKGROUND INFORMATION FORM 

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ADULT BACKGROUND INFORMATION FORM 
(To be completed by adult participants at baseline) 
 
Name:_____________________________________ Date:____________  
Date of 
Birth:____________ 
Phone Numbers: 
Home ________________ 
Work ________________ 
Cell  
_________________ 
Email: 
______________________________ 
Do you prefer:   Skype           Other: ___________  
                           Facetime     
Demographics 
Sex: 
 Male 
 Female 
Race: 
 
 
Ethnicity: 
❑White    
❑Asian      
❑Unknown 
Hispanic or 
Latino  
❑African American/Black 
❑Native Hawaiian/Pacific Islander 
❑American Indian/Alaskan Native   
 Not Hispanic or Latino     
 Unknown 
Marital Status: 
 Single 
 Married             Divorced             Separated             Widowed 
Occupational Status: 
 
  Are you currently working?  No    Yes     On disability    
If working, hours per week:  ______ 
Occupation: 
_____________________________________________________________________ 
How long at current job?    ________________  
  Are you currently in school (e.g., college, vocational school, taking a class)?  No    Yes 
       If yes, please specify:_______________________ ______________________________________ 
  Are you receiving/Did you receive any special educational accommodations?  No    Yes 
Level of Independent Living: 
    I take care of myself (i.e., cooking, cleaning, bathing, dressing) independently. 
    I need some help taking care of myself. 
    I live in residential care. 
    Other (please specify:____________________________________________________________) 
Educational History 
 
   Highest grade level in school completed (1 – 12):  
   Years of college completed (1 – 4): 
   Years of graduate/professional school completed: 
________ years 
________ years 
________ years 
School Performance:  
 
High School:   
College:   
Average    Above Average     Below Average 
Average    Above Average     Below Average      Not     
                                                                                   applicable 
Psychological/Neurological History  
 
Have you been diagnosed with any of the following: 
 
Attention Deficit: 
No     Yes  
Learning Disability: No     Yes    Specify type: ______________________________ 
Depression: 
No     Yes  
Anxiety: 
No     Yes  
Other psychiatric   
 diagnosis:  
No     Yes    Specify diagnosis: ______________________________ 
 

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9.3 
APPENDIX C: ADULT PAIN QUESTIONNAIRE 
(Self report form for 18+ years) 
Pain Interference Index – Adult 
 
Below you will find a list of questions about you and your pain. Please answer each question by 
circling a number between 0 and 6. 
 
Please note that we are asking about your pain during the last week.  
Has your pain: 
Not at 
all 
 
 
Some 
 
 
Comp-
letely 
1. 
made it difficult for you to do work (in or 
outside the home)? 
0 
1 
2 
3 
4 
5 
6 
2. 
made it difficult for you to do activities 
outside of work (leisure activities)? 
0 
1 
2 
3 
4 
5 
6 
3. 
made it difficult for you to spend time with 
friends and family members? 
0 
1 
2 
3 
4 
5 
6 
4. 
affected your mood? 
0 
1 
2 
3 
4 
5 
6 
5. 
affected your ability to do physical activities 
(like run, walk up stairs, play sports, do 
chores)?  
0 
1 
2 
3 
4 
5 
6 
6. 
affected your sleep? 
0 
1 
2 
3 
4 
5 
6 
 
Adapted by the Neurobehavioral Group, NCI (8/23/13) 
 
  
 
 

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9.4 
APPENDIX D: PAIN INTERFERENCE –SHORT FORM 8A -ADULT 
 

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9.5 
APPENDIX E: PAIN INTERFERENCE –SHORT FORM 8A –PEDIATRIC 
 

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9.6 
APPENDIX F:  PEDSQL NEUROFIBROMATOSIS TYPE 1 MODULE 
Neurofibromatosis Type 1: QOL instrument- Pediatric 
DIRECTIONS 
This survey is for individuals with NF 1.  Neurofibromatosis type 1 sometimes 
causes special problems.  Please tell us how much of a problem each one has 
been for you during the past ONE month by circling: 
0 if it is never a problem 
1 is it is almost never a problem 
2 if it is sometimes a problem 
3 if it is often a problem 
4 if it is almost always a problem 
There are no right or wrong answers.  
If you do not know an answer, take your best guess. 
Thank you for your help! 
 
In the past ONE month, how much of a problem has this been for you… 
PHYSICAL 
FUNCTIONING 
(problems with…) 
Never 
Almost 
never 
Some-
times 
Often 
Almost 
Always 
1.  Feeling physically weak 
0 
1 
2 
3 
3 
2. Walking more than one 
block 
0 
1 
2 
3 
3 
3. Climbing stairs 
0 
1 
2 
3 
3 
4. Running 
0 
1 
2 
3 
3 
5. Doing a sports activity or 
exercise 
0 
1 
2 
3 
3 

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6. Lifting something heavy 
0 
1 
2 
3 
3 
7. Doing chores around the 
house 
0 
1 
2 
3 
3 
 
In the past ONE month, how much of a problem has this been for you… 
DAILY ACTIVITIES 
(problems with…) 
Never 
Almost 
Never 
Some-
times 
Often 
Almost 
Always 
1. Putting on shoes 
0 
1 
2 
3 
4 
2. Buttoning my shirt 
0 
1 
2 
3 
4 
3. Combing my hair 
0 
1 
2 
3 
4 
4. Getting into the bathroom to 
use the toilet 
0 
1 
2 
3 
4 
5. Undressing to use the toilet 
0 
1 
2 
3 
4 
6. Getting in and out of 
bathtub or shower 
0 
1 
2 
3 
4 
7. Brushing my teeth 
0 
1 
2 
3 
4 
8. Eating with a fork or knife 
0 
1 
2 
3 
4 
9. Using a phone 
0 
1 
2 
3 
4 
10. Shopping 
0 
1 
2 
3 
4 
11. Managing money 
0 
1 
2 
3 
4 
12. Driving 
0 
1 
2 
3 
4 
 
 
 
 

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Neurofibromatosis Type 1: QOL instrument- Adult 
DIRECTIONS 
This survey is for individuals with NF 1.  Neurofibromatosis type 1 sometimes 
causes special problems.  Please tell us how much of a problem each one has 
been for you during the past ONE month by circling: 
0 if it is never a problem 
1 is it is almost never a problem 
2 if it is sometimes a problem 
3 if it is often a problem 
4 if it is almost always a problem 
There are no right or wrong answers.  
If you do not know an answer, take your best guess. 
Thank you for your help! 
 
In the past ONE month, how much of a problem has this been for you… 
PHYSICAL 
FUNCTIONING 
(problems with…) 
Never 
Almost 
never 
Some-
times 
Often 
Almost 
Always 
1.  Feeling physically weak 
0 
1 
2 
3 
3 
2. Walking more than one 
block 
0 
1 
2 
3 
3 
3. Climbing stairs 
0 
1 
2 
3 
3 
4. Running 
0 
1 
2 
3 
3 
5. Doing a sports activity or 
exercise 
0 
1 
2 
3 
3 
6. Lifting something heavy 
0 
1 
2 
3 
3 

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7. Doing chores around the 
house 
0 
1 
2 
3 
3 
 
 
In the past ONE month, how much of a problem has this been for you… 
DAILY ACTIVITIES 
(problems with…) 
Never 
Almost 
Never 
Some-
times 
Often 
Almost 
Always 
1. Putting on shoes 
0 
1 
2 
3 
4 
2. Buttoning my shirt 
0 
1 
2 
3 
4 
3. Combing my hair 
0 
1 
2 
3 
4 
4. Getting into the bathroom to 
use the toilet 
0 
1 
2 
3 
4 
5. Undressing to use the toilet 
0 
1 
2 
3 
4 
6. Getting in and out of 
bathtub or shower 
0 
1 
2 
3 
4 
7. Brushing my teeth 
0 
1 
2 
3 
4 
8. Eating with a fork or knife 
0 
1 
2 
3 
4 
9. Using a phone 
0 
1 
2 
3 
4 
10. Shopping 
0 
1 
2 
3 
4 
11. Managing money 
0 
1 
2 
3 
4 
12. Driving 
0 
1 
2 
3 
4 
 
 
 

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9.7 
APPENDIX G:  PAIN ANXIETY SYMPTOMS SCALE-20 (PASS-20) 
Name: ______________________________ 
 
 
Date: _______________ 
PAIN ANXIETY SYMPTOMS SCALE-20 (PASS-20) 
 
Individuals who experience pain develop different ways to respond to that pain.  We would 
like to know what you do and what you think about when in pain.  Please use the rating scale 
below to indicate how often you engage in each of the following thoughts or activities.  Circle 
any number from 0 (NEVER) to 5 (ALWAYS) for each item.   
 
 
 
 
 
 
 
 
1. I think that if my pain gets too severe, it will never decrease 
 
0 1 2 3 4 5 
2. When I feel pain I am afraid that something terrible will happen 
 
0 1 2 3 4 5 
3. I go immediately to bed when I feel severe pain 
 
0 1 2 3 4 5 
4. I begin trembling when engaged in activity that increases pain 
 
0 1 2 3 4 5 
5. I can’t think straight when I am in pain 
 
0 1 2 3 4 5 
6. I will stop any activity as soon as I sense pain coming on 
 
0 1 2 3 4 5 
7. Pain seems to cause my heart to pound or race 
 
0 1 2 3 4 5 
8. As soon as pain comes on I take medication to reduce it 
 
0 1 2 3 4 5 
9. When I feel pain I think that I may be seriously ill 
 
0 1 2 3 4 5 
10. During painful episodes it is difficult for me to think of anything else besides the pain  
0 1 2 3 4 5 
11. I avoid important activities when I hurt 
0 1 2 3 4 5 
12. When I sense pain I feel dizzy or faint 
0 1 2 3 4 5 
13. Pain sensations are terrifying 
 
0 1 2 3 4 5 
14. When I hurt I think about the pain constantly 
0 1 2 3 4 5 
15. Pain makes me nauseous (feel sick) 
 
 
0 1 2 3 4 5 
16. When pain comes on strong I think I might become paralyzed or more disabled 
0 1 2 3 4 5 
17. I find it hard to concentrate when I hurt 
0 1 2 3 4 5 
18. I find it difficult to calm my body down after periods of pain 
0 1 2 3 4 5 
19. I worry when I am in pain 
0 1 2 3 4 5 
20. I try to avoid activities that cause pain 
 
0 1 2 3 4 5 
NEVER                       ALWAYS 

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9.9 
APPENDIX H:  CENTER FOR EPIDEMIOLOGICAL STUDIES-DEPRESSION SCALE (CES-D 
Name: ______________________________ 
 
 
Date: _______________ 
CES-D 
Please indicate how often you have felt this way during the last week. 
3 = Most or all of the time (5 to 7 days a week). 
2 = Occasionally or a moderate amount of time (3 to 4 days a week). 
1 = Some or a little of the time (1 to 2 days a week). 
0 = Rarely or none of the time (less than once a week). 
1.  I was bothered by things that usually don't bother me.  
0       1       2       3 
2.  I did not feel like eating: my appetite was poor.   
0       1       2       3 
3.  I felt that I could not shake off the blues.   
0       1       2       3 
4.  I felt that I was just as good as other people. 
0       1       2       3 
5.  I had trouble keeping my mind on what I was doing. 
0       1       2       3 
6.  I felt depressed. 
0       1       2       3 
7.  I felt that everything I did was an effort.  
0       1       2       3 
8.  I felt hopeful about the future. 
0       1       2       3 
9.  I thought my life had been a failure.  
0       1       2       3 
10.  I felt fearful.  
0       1       2       3 
11.  My sleep was restless.  
0       1       2       3 
12.  I was happy. 
0       1       2       3 
13.  I talked less than usual. 
0       1       2       3 
14.  I felt lonely. 
0       1       2       3 
15.  People were unfriendly. 
0       1       2       3 
16.  I enjoyed life. 
0       1       2       3 
17.  I had crying spells. 
0       1       2       3 
18.  I felt sad. 
0       1       2       3 
19.  I felt that people disliked me. 
0       1       2       3 
20.  I could not get going. 
0       1       2       3 
 
 
 

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9.10 APPENDIX I: NUMERIC RATING SCALE-11 (NRS-11) 
 
I am going to ask you two questions about how much your plexiform neurofibroma 
tumor hurts. 
 
First, where is the location of your most important tumor pain?  
(Specify the location of that tumor:___________________________________________). 
 
Below are lines with numbers from 0 to 10 where 0 means no pain and 10 means the worst 
pain you can imagine.  
 
1. Please circle the one number that best describes that most important tumor pain at its 
worst during the past week.   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 0 
1 
2 
 3 
 4 
5 
6 
7 
8 
 9 
10 
No  
 
 
 
 
Worst pain 
pain 
 
 
 
 
you can imagine 
 
 
2. Please circle the one number that best describes your overall tumor pain at its worst 
during the past week. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 0 
1 
2 
 3 
 4 
5 
6 
7 
8 
 9 
10 
No  
 
 
 
 
Worst pain 
pain 
 
 
 
 
you can imagine 
 
 
 
 

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9.11 APPENDIX J: CHRONIC PAIN ACCEPTANCE QUESTIONNAIRE (CPAQ) 
 

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9.12 APPENDIX K: PSYCHOLOGICAL INFLEXIBILITY IN PAIN SCALE (PIPS) 
 
Below you will find a list of statements.  Please rate how true each statement is for you right now 
by circling a number next to it. 
 
1  
2 
 
3 
 
4 
 
5 
 
6 
 
7 
Never  
  Very  
Seldom 
Sometimes 
  Often  
Almost           Always 
  true  
  rarely  
  true  
    true  
   true  
always  
  true 
 
 
   true  
 
 
 
 
 
 
  true  
______________________________________________________________________________ 
1. I cancel planned activities when I am in pain. 
 
 
 
    1   2   3   4   5   6   7  
 
2. I say things like “I don’t have energy”, “I 
am not well enough”, “I don’t have time”, “I 
don’t dare”, “I have too much pain”, “I feel 
too bad”, or “I don’t feel like it”. 
    1   2   3   4   5   6   7  
 
3. I need to understand what is wrong in order to move on.  
 
    1   2   3   4   5   6   7 
 
4. Because of my pain, I no longer plan for the future. 
 
 
    1   2   3   4   5   6   7 
 
5. I avoid doing things when there is a risk it will hurt or make  things worse. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    1   2   
3   4   5   6   7 
 
6. It is important to understand what causes my pain.  
 
 
    1   2   3   4   5   6   7 
 
7. I don’t do things that are important to me to avoid pain.  
 
    1   2   3   4   5   6   7 
 
8. I postpone things because of my pain.  
 
 
 
 
    1   2   3   4   5   6   7 
 
9. I would do anything to get rid of my pain.  
 
 
 
    1   2   3   4   5   6   7 
 
10. It’s not me that controls my life, it’s my pain. 
 
 
    1   2   3   4   5   6   7 
 
11. I avoid planning activities because of my pain 
 
 
    1   2   3   4   5   6   7 
 
12. It is important that I learn to control my pain.  
 
 
    1   2   3   4   5   6   7 
 
 

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9.13 APPENDIX L: LIFE EVENTS CHECKLIST 
Name:  
 
      
__________  
 
 
Date:  
 
 
 
Please place a checkmark next to the events that you have experienced during the past 6 months.   
_____ 1.  Birth or adoption of a sibling by parent 
____ 18a  Hospitalization  
          
         18b  Please specify # of days:  
_____ 2.  Marriage of a parent 
              ___ 1-5  ___6-10  ___11-15  ___16+ 
         18c  Reason hospitalized:_________________________ 
_____ 3.  Divorce of parents 
____ 19a  Hospitalization of your parent  
          
         19b  Please specify # of days:      
_____ 4.  Marital separation of parents 
              ___ 1-5  ___6-10  ___11-15  ___16+ 
_____ 5.  Death of a grandparent 
____ 20. Discovery of a family member's serious  
               illness  
 
_____  6.  Close family member leaving home  
                 for an extended period 
____ 21. Discovery of a serious illness   
              (please specify:________________________) 
_____ 7.  Loss of job by parent 
____ 22. Disclosure of diagnosis to others 
_____ 8.  Financial hardship (e.g., difficulty  
                  paying bills) 
____ 23. One or more changes in residence 
_____ 9.  Family gets financial assistance 
____ 24. Family member experiencing problems  
               with drugs or alcohol 
_____ 10. Death of a parent 
____25. Substantial change in peer group 
 
_____ 11. Death of a sibling 
_____26. Teased in school/college 
_____ 12. Death of a peer 
____ 27. Problems with school administration 
_____ 13. Move to a new school/college/job 
____ 28. Teacher reporting behavior problems in  
                school/college 
_____14. Repeated a grade or college course 
____ 29.  Other stressful event occurring in family 
         Please specify                                                                 . 
_____ 15. Suspension from school/college 
____ 30. Experienced a change in primary caregiver(s).   
         Please specify                                                                 .  
_____ 16. Decline in school grades or work 
performance 
 
 
____ 31. Parent has serious medical condition.   
         Please specify                                                                 . 
_____ 17. Significant number of school/work 
absences (16 or more) 
 
____ 32.  Giving birth or adopting a child 
                                               

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_____33.  Getting married  
_____34. Separated from spouse or significant other 
_____35. Divorced 
_____36. Death of your spouse  
_____37. Death of your child 
_____38. Experiencing legal issues 
_____39. Experiencing stress related to a serious illness  
_____40. Discovery of a serious illness for your child 
_____41.a Hospitalization of your child 
         41.b Please specify # of days 
               ___ 1-5  ___6-10  ___11-15  ___16+               
_____42. Loss of job 
_____43. Other stressful event related to work or school.   
           
Please specify                                                                 . 
 
   Check here if none of the above events have occurred in your life in the past 6 months. 
 
 
Please take a few seconds to make sure you have reviewed every item on page 1 and page 2.  Thank you 
for filling out this form! 
 
 
 
 
 
 

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9.14 APPENDIX M:  PAIN MANAGEMENT INVENTORY 
Pain Management Inventory 
(1) In the past month, have you taken any medication for your pain?      Yes    No 
If no, skip to question (2).  If yes, please provide the following information: 
 
   Medication 1:  Name _____________________    Dose ______________   
 
How often do/did you take this medication? (check one)  
 

 

 

 

 

Less than 
once a month 
1-3 times a 
month 
Once a week 
2-4 times a 
week 
Daily 
 
   Medication 2:  Name _____________________    Dose ______________   
 
How often do/did you take this medication? (check one)  
 

 

 

 

 

Less than 
once a month 
1-3 times a 
month 
Once a week 
2-4 times a 
week 
Daily 
 
(2) In the past month, have you done any behavioral techniques for the purpose of managing your pain 
besides ACT (for example, yoga, relaxation, exercise)?   Yes   No 
 
If yes, please list and provide the following information: 
 
 
1:  Name _________________________ 
 
 
How often do you do this?  
 

 

 

 

 

Less than 
once a month 
1-3 times a 
month 
Once a week 
2-4 times a 
week 
Daily 
 
     
 
2:  Name _________________________ 
 
 
How often do you do this?  
 

 

 

 

 

Less than 
once a month 
1-3 times a 
month 
Once a week 
2-4 times a 
week 
Daily 
(3) In the past month, have you done any other techniques for the purpose of managing your pain?   Yes   
No 
If yes, please list and provide the following information: 
 
Name _________________________ 
 
 
How often do you do this?  
 

 

 

 

 

Less than 
once a month 
1-3 times a 
month 
Once a week 
2-4 times a 
week 
Daily 
 

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9.15 APPENDIX N:  PAIN MANAGEMENT INVENTORY 
Pain Management Inventory – 6 month follow-up 
 
(1) In the past month, have you taken any medication for your pain?      Yes    No 
If no, skip to question (2).  If yes, please provide the following information: 
 
   Medication 1:  Name _____________________    Dose ______________   
 
How often do/did you take this medication? (check one)  
 

 

 

 

 

Less than 
once a month 
1-3 times a 
month 
Once a week 
2-4 times a 
week 
Daily 
 
   Medication 2:  Name _____________________    Dose ______________   
 
How often do/did you take this medication? (check one)  
 

 

 

 

 

Less than 
once a month 
1-3 times a 
month 
Once a week 
2-4 times a 
week 
Daily 
 
(2) In the past month, have you done any behavioral techniques for the purpose of managing your pain 
besides ACT (for example, yoga, relaxation, exercise)?   Yes   No 
If yes, please list and provide the following information: 
 
 
1:  Name _________________________ 
 
 
How often do you do this?  
 

 

 

 

 

Less than 
once a month 
1-3 times a 
month 
Once a week 
2-4 times a 
week 
Daily 
 
     
 
2:  Name _________________________ 
 
 
How often do you do this?  
 

 

 

 

 

Less than 
once a month 
1-3 times a 
month 
Once a week 
2-4 times a 
week 
Daily 
 

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(3) In the past month, have you done any other techniques for the purpose of managing your pain?   Yes   
No 
If yes, please list and provide the following information: 
 
 
Name _________________________ 
 
 
How often do you do this?  
 

 

 

 

 

Less than 
once a month 
1-3 times a 
month 
Once a week 
2-4 times a 
week 
Daily 
 
(4) In the past SIX months, have you had any new treatments (e.g., surgeries, alternative therapies) for your 
NF1?     Yes   No 
If yes, please specify:   ________________________________________ 
Date of Treatment:  ________________________ 
 
 

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9.17 APPENDIX O: ACT INVENTORY 
 
1. In the past month, how often have you engaged in the following strategies? (choose only one response)   
 
a. Mindfulness (e.g., mindful breathing, responding mindfully to your pain) 
 

 

 

 

 

Not at all 
1 – 2 times 
Once a week 
2 – 3 times a 
week 
Daily 
 
b. Noticing that your thoughts about your pain are just thoughts, and not judging them 
 

 

 

 

 

Not at all 
1 – 2 times 
Once a week 
2 – 3 times a 
week 
Daily 
 
c. Doing something you wanted to do even though you were in pain 
 

 

 

 

 

Not at all 
1 – 2 times 
Once a week 
2 – 3 times a 
week 
Daily 
 
d. Listening to your mindfulness CD (or downloaded audio) 
 

 

 

 

 

Not at all 
1 – 2 times 
Once a week 
2 – 3 times a 
week 
Daily 
 
e. Reading ACT materials (e.g., online or in your workbook) 
 

 

 

 

 

Not at all 
1 – 2 times 
Once a week 
2 – 3 times a 
week 
Daily 
 
2. In the past month, when have you engaged in strategies taught in the study? (check all that apply) 
 

 

 

 

 

Never 
When I 
remember 
When I have 
pain 
When I am 
upset 
Daily 
 
3.  How much did you like doing this study?   
 

 

 

 

 

Not at all 
Just A Little 
Some 
Pretty Much 
A Lot 
4. How helpful did you find the in-person ACT training sessions at the NIH?  
 

 

 

 

 

Not at all 
Just A Little 
Some 
Pretty Much 
A Lot 
5. How many of the weekly emails did you read?  
 

 

 

 

 

None 
A few (1 or 2) 
About half (3-5) 
Most (6 or 7) 
All (8) 
 

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6. How helpful did you find the weekly emails? 
 

 

 

 

 

Not at all 
Just A Little 
Some 
Pretty Much 
A Lot 
 
7. How helpful did you find the video chat sessions? 
 

 

 

 

 

Not at all 
Just A Little 
Some 
Pretty Much 
A Lot 
  
 
 

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9.18 APPENDIX P: GLOBAL IMPRESSION OF CHANGE SCALE 
 
Name: ____________________________ 
Date: ________________ 
 
Think about how much pain interferes with your life currently.  Compared to when you first started this 
study, would you say this is:  
 
 1 Very Much Improved  
 2 Much Improved 
 3 Minimally Improved 
 4 No Change 
 5 Minimally Worse 
 6 Much Worse 
 7 Very Much Worse 
 
 
 
 
 
 
  
 
 
 
References: Guy, 1976; Farrar et al., 2001 (DOI: 10.1016/S0304-3959(01)00349-9). 
 
 
 
 
 

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9.19 APPENDIX Q: ACT WORKBOOK 
 
 
ACT WORKBOOK 
 
 
 
Psychology Group 
Behavioral Health Core 
National Institutes of Health 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Noticing Your Pain 
 
Write down any thoughts that come up when you think about your worst pain.   
 
 
 
 
 
 
 
What Have you Tried? 
 
What have you tried to get rid of your pain?  What do you do when your pain is bad?   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Mindfulness in Our Daily Lives 
 
1. Mindfulness in Your Morning Routine 
 
Pick an activity that is part of your morning routine, like brushing your teeth, eating breakfast, or taking a 
shower.  When you do it, totally focus on what you’re doing – the way your body moves, the taste, the touch, 
the smell, the sound, and so on.  Notice what is happening with an attitude of being open and curious.   
 
For example, when you are brushing your teeth, notice the feel of the toothbrush in your hand.  Notice the 
smell of the toothpaste and what it looks like as you squeeze some onto your brush.  Notice the way it feels 
in your mouth, and as you brush along your front teeth, back teeth, gums, and tongue.  Notice the sound of 
the brush going up and down or side to side in your mouth.  Notice the sound of the running water, and how 
it feels to spit into the sink.   
 
 
2. Mindfulness of Domestic Chores 
 
Pick one of your chores, like making your bed, cooking, or setting the table, and do it mindfully.  For 
example, when making your bed, notice the color and shape of the pillows, and the pattern made by the 
creases in the sheets.  Notice the feel of the bedspread in your hands as you pull it up, and the movement of 
your arms and shoulders and hands.   
 
If you feel yourself being bored or frustrated, just notice it and then bring your attention back to what you’re 
doing.  Again and again, your attention will wander.  As soon as you realize this has happened, gently notice 
it, and then bring your attention back to what you are doing.   
 
 
3. Mindfulness of Pleasant Activities 
 
Pick an activity that you enjoy, such as listening to music, eating lunch, stroking the cat, playing with the 
dog, walking in the park, having a soothing hot bath, and so on.  Do this activity mindfully – engage in it 
fully, using all five of your senses, and enjoy every moment.  If and when your attention wanders, as soon as 
you realize it, notice what distracted you, and re-engage in whatever you are doing.    
 
 
 
 
 
 
 
Adapted from Act Made Simple by Russ Harris.   
 
 
 

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Examples of Defusion Metaphors 
 
When you notice a distressing or unpleasant thought, visualize… 
 
• placing the thought on a leaf floating by on a stream 
 
• the words scrolling by on a computer screen 
 
• cars passing on the street outside your window 
 
• the words printed on a sign, being held by people walking by in a parade 
 
• placing the thought on a cloud as it slowly drifts through the sky 
 
 
 
 
Which image do you like the best?   

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End of day 1: 
Keep Going… 
 
* Take a walk.   Walk around the neighborhood (or clinical center, Inn) with the goal being 
just to talk a walk.  Focus on internal sensations (your feet as they touch the ground, the 
way your arms swing back and forth) and external stimuli (sounds of birds chirping or traffic, 
breezes).  Avoid talking to others.   
 
 
* Mindfulness Exercise.  Do mindful breathing or a body scan for 5 minutes tonight. 

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Values Assessment 
 
 
Value 
Importance 1-10 
Success 1-10 
Education/learning/personal growth 
 
 
 
 
 
Employment 
 
 
 
 
 
Friendship/social 
 
 
 
 
 
Recreation/hobbies 
 
 
 
 
Spirituality/religion 
 
 
 
 
Community 
 
 
 
 
Health/physical well-being 
 
 
 
 
 
Couples/intimate relationship 
 
 
 
 
Family 
 
 
 
 
 
 
 
 
 

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Tips for Setting Goals 
 
 
Goals should be SMART:  
 
Specific: Specify the actions you will take, when and where you will do so, and who or what 
is involved.  A non-specific goal is: “I will spend more time with my family.”  A specific goal is 
“I will go for a walk with my sister on Saturday morning.”   
 
Meaningful: The goals should be personally meaningful to you.  If it is genuinely guided by 
your values then it will be meaningful.   
 
Adaptive: Does the goal help you take your life forwards in a direction that, as far as you can 
predict, is likely to improve the quality of your life?  
 
Realistic: The goals should be realistically achievable.  Take into account your health, 
competing demands on your time, financial status, and whether you have the skills to 
achieve it.   
 
Time-bound: To increase the specificity of the goal, set a day, date and time for it.  If this is 
not possible, set as accurate a time limit as you can.   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Goals Form 
 
Step 1: Write one of your values here:  ____________________________________ 
 
 
Step 2: Think about goals you can set for yourself that will help you live more consistently with the 
value indicated above.   
 
Step 3: Write some goals below: 
 
* An Immediate Goal (something small, simple, easy, I can do in the next 24 hours) 
 
 
* Short-term Goals (things I can do over the next few days and weeks) 
 
 
* Medium-term Goal(s) (things I can do over the next few weeks and months)  
 
 
* Long-term Goal(s) (things I can do over the next few months and years) 
 
 
___________________________________________________________________________ 
Step 1: Write one of your values here:  ____________________________________ 
 
 
Step 2: Think about goals you can set for yourself that will help you live more consistently with the 
value indicated above.   
 
Step 3: Write some goals below: 
 
* An Immediate Goal (something small, simple, easy, I can do in the next 24 hours) 
 
 
* Short-term Goals (things I can do over the next few days and weeks) 
 
 
* Medium-term Goal(s) (things I can do over the next few weeks and months)  
 

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* Long-term Goal(s) (things I can do over the next few months and years) 
 
 
Facing Barriers – Part 1 
 
Choose one of your goals from the goals form that you think you may have difficulty with 
and write it here:  
 
_____________________________________________________________ 
 
Now write down the possible barriers that may arise that could prevent you from 
accomplishing this goal:  
 
1. ___________________________________________________________ 
 
2. ___________________________________________________________ 
 
3. ___________________________________________________________ 
 
4. ___________________________________________________________ 
 
 
Now ask yourself two questions:  
Are you willing to have those barriers show up and still move towards your goal?   
(If not, practice expansion or re-evaluate your goals/values) 
 
and  
 
What will you do when barriers arise?   
 
 
 
 
 
 
 
 
 

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Recruiting Others: Sample Script 
 
You are very important to me, and I really need your support right now.  I have set some 
goals for myself that will help me live according to my values.  I realize that it is normal and 
okay to have pain.  I understand that it’s hard for you to see me in pain and to encourage 
me to do things when I’m really down or in pain.  It would mean a lot to me if you would do 
it anyway, like a coach.  I will care about you no matter what, but I really want to do some 
important things and you can help me with this.  Are you willing to support me in my values 
and goals, even when it’s hard for you?  This is what I want for my life.   
 
 
 
 
 
 

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9.20 APPENDIX R:  PRACTICE EXERCISES 
Continue Practicing At Home!! 
 
Mindfulness Exercises: Simple Ways to Get Present 
 
Take Ten Breaths   This is a simple exercise to center yourself and connect with your environment. 
Practice it throughout the day, especially any time you find yourself getting caught up in your 
thoughts and feelings. 
1. Take ten slow, deep breaths. Focus on breathing out as slowly as possible until the lungs are 
completely empty—and then allow them to refill by themselves. 
2. Notice the sensations of your lungs emptying. Notice them refilling. Notice your rib cage rising 
and falling. Notice the gentle rise and fall of your shoulders. 
3. See if you can let your thoughts come and go as if they’re just passing cars, driving past outside 
your house. 
4. Expand your awareness: simultaneously notice your breathing and your body. Then look around 
the room and notice what you can see, hear, smell, touch, and feel. 
 
Drop Anchor  This is another simple exercise to center yourself and connect with the world around 
you. Practice it throughout the day, especially any time you find yourself getting caught up in your 
thoughts and feelings. 
1. Plant your feet into the floor. 
2. Push them down—notice the floor beneath you, supporting you. 
3. Notice the muscle tension in your legs as you push your feet down. 
4. Notice your entire body—and the feeling of gravity flowing down through your head, spine, and 
legs into your feet. 
5. Now look around and notice what you can see and hear around you. Notice where you are and 
what you’re doing. 
 
Notice Five Things  This is yet another simple exercise to center yourself and engage with your 
environment. Practice it throughout the day, especially any time you find yourself getting caught 
up in your thoughts and feelings. 
1. Pause for a moment 
2. Look around and notice five things that you can see. 
3. Listen carefully and notice five things that you can hear. 
4. Notice five things that you can feel in contact with your body (for example, your watch against 
your wrist, your trousers against your legs, the air on your face, your feet upon the floor, your back 
against the chair). 
5. Finally, do all of the above simultaneously 
 
© Russ Harris: ACT Made Simple handouts 
 

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There are many poems, books, songs, TV shows, and movies where you can find ACT-related 
concepts.  For example, the following poem illustrates the concept of mindfulness.   
 
When Singing, Just Sing – Life as Meditation 
When sitting, just sit. 
When eating, just eat. 
When walking, just walk. 
When talking, just talk. 
When listening, just listen. 
When looking, just look. 
When touching, just touch. 
When thinking, just think. 
When playing, just play. 
And enjoy the feeling of each moment and each day. 
 
by Narayan Liebenson Grady 
 
 
See if you can notice other examples of ACT themes you might see or hear!   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Other Ways to Practice ACT in Your Life 
 
* Take 10.  Set the alarm on your watch or cell phone to go off 2 times during the next hour.  
If you don’t have an alarm, write a note on a small piece of paper that you carry around or 
put somewhere visible to remind you.  When you hear the alarm or notice the paper, stop 
what you are doing and take 10 seconds to pay attention to what is going on around you 
and within you.   
 
* Search online for “mindfulness bell”.  You can set a timer so that a bell rings periodically to 
remind you to slow down, get centered, and notice.  
 
* Wear a particular piece of jewelry or put a small sticker or pin on your wallet or purse.  Let 
this be your “values” symbol.  It could also be a photo of a special person in your life (like 
your child or partner).  Choose a value (a thing or person) that you want it to represent, 
then try to think of that value every time you see the symbol.  Let it remind you of how 
important that value is to you, and encourage you to do something to move toward that 
value today.   
 
 
 
 
 
 
 
 

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References and Resources 
 
Books 
Get Out of Your Mind and Into Your Life: The New Acceptance and Commitment Therapy 
By Steven Hayes  
 
Mindfulness for Beginners: Reclaiming the Present Moment and Your Life 
By Jon Kabat-Zinn 
 
ACT Made Simple: An Easy-to-Read Primer on Acceptance and Commitment Therapy  
By Russ Harris 
 
CDs/Downloads/Audio 
Mindfulness Meditation for Pain Relief: Guided Practices for Reclaiming Your Body and Your 
Life  
By Jon Kabat-Zinn 
 
 
Websites 
 
http://www.actmindfully.com.au/ 
 
http://www.acceptandchange.com/audio/ 
 
http://www.drluoma.com/actresources.html#materials 
 
http://julianmcnally.com/Content/psychological-services/ 
 
 
 
 
 

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9.21 APPENDIX S: VIDEO CHAT MANUAL 
Video chat Sessions 
 
Session 1 (week 2) 
 
Committed Action 
 
• Ask patient about their thoughts, impressions, etc. since the in-person sessions.  What have the last 
two weeks been like?  Discuss content of weekly email briefly.   
 
• Ask about any difficulties that have come up – focus on willingness; challenge of sitting with, or 
acknowledging those difficult thoughts and feelings in the service of their values.   
 
• Remind them to practice mindful breathing – ask about how that is going.   
 
• Check in on goals; what short-term goals did they accomplish?  Do they need help adjusting any 
goals?   
 
• Revisit concept of committed action and what they are willing to have in order to live a valued life.   
 
• Use metaphors, exercises from in-person sessions as reminders, as necessary…i.e., “How tightly are 
you holding that thought?” “Thank your mind for that thought,”  “Invite that thought to be present 
when you move towards your values.” 
 
 
Session 2 (week 4) 
 
Noticing Progress 
 
• Ask patient about their progress – how do they feel they have been doing?  What has gotten in the 
way?  What positive changes have they noticed, if any?  Discuss content of weekly email briefly.  
 
Ideas to explore:  
• Sometimes we are so wrapped up in thinking about moving from one goal to the next that we 
forget to notice how much we have accomplished.  Help patient take a minute to really notice any 
changes s/he might be experiencing and the progress made so far.  (See if they can come up with 
behaviors they have engaged in that are associated with one or more of their values) 
 
• Take a moment to really focus on that sense of accomplishment.  What comes up…pride?  
Satisfaction?  Frustration that it wasn’t more?  What does that (pride) feel like to you? See if you 
can sit with that feeling for 20 seconds, just noticing it without doing anything else.   
 
• Some people have a hard time with this…if this is the case, explore why: Is it that you haven’t 
taken the time to notice what’s going on with your emotions or behavior? They don’t understand 
some of the concepts?  

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• Clarify any questions the patient has about any of the concepts they are struggling with.   
 
 
Session 3 (week 6) 
 
Self-compassion and Review of Committed Action 
 
• How have the techniques you have learned been working in other areas of your life besides pain?  Ask 
for examples…relationships, work, school, leisure time, etc.  Discuss content of weekly email briefly.   
 
• Revisit goals.  Discuss progress, and set specific goals for them to work on between now and their return 
visit.   
 
• Often people with pain tend to experience anger or frustration related to various pain-related challenges: 
o Why can’t I control my pain better? 
o Why can’t I learn to cope better? 
o Resentment at family members or others who “don’t understand what it’s like”, and guilt for 
feeling that way 
o Anger at doctors for not making it better 
 
• Explore ideas of:  
o Connecting with others with chronic pain (and NF, and PNs)  
o Forgiveness and kindness exercises (pgs 274-278, Radical Acceptance) 
▪ Select phrases that resonate in the moment 
▪ Say the phrase out loud 
o Allowing the anger to be there but not letting it control us 
▪ Connect with the idea that the anger (or other distressing thoughts and emotions) are 
usually there to try to protect you (not always helpful!) 
o Recognizing the impermanence of waves of anger, sadness, anxiety, and even physical pain 
 
• Cultivating self-compassion in our daily lives – instead of continuing to be on auto-pilot, how do we 
remember to practice mindfulness and self-care?  
 
• How self-compassion can help keep us on track towards values (re-establish committed action) 
 
 
 

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Weekly E-mails 
 
Week One 
Noticing Your Thoughts 
We talked before about how our minds are sometimes helpful, like when they remind us that we 
need to get to work or school on time.  We also talked about the fact that our minds are not so 
helpful sometimes.   
Now that you are back home, have you noticed any thoughts your mind has had about this study?  
Maybe your mind has said, “This ACT stuff is crazy!” or “It might work for other people, but it’s 
never going to work for me!”  Or maybe your mind has told you that it is going to work – right 
away!  It might be saying “Hurry up and feel better!”   
If your mind has been telling you anything similar to these thoughts, it certainly makes sense.  All 
of those thoughts are understandable and normal.  The important thing is that you NOTICE the 
thoughts (that’s being mindful), and just let them come and go (that’s acknowledging).  Maybe 
even thank your mind for those thoughts, and then choose how to behave based on your 
VALUES!    
Take about 30 seconds right now to reflect on the above paragraphs, and then read on for your 
weekly activities…  
This week: 
1) Focus on one of the goals you set for yourself when we met at the NIH that you can work on 
this week.  When you are working towards that goal, remind yourself of the value to which it’s 
related.  You might say to yourself, “I am doing this because ________.”  Fully acknowledge how 
it feels to work towards something you truly value.   
2) Write that same value down on a piece of paper and put it somewhere in your house where you 
will see it every morning, like on your dresser or taped to your mirror, to help you remember 
it.  Every time you notice it, really think about how important that value is to you.  See if this 
makes it easier to reach your goal!   
 
Week Two 
Be Mindful When Doing…Anything!   
 
We have talked a lot about mindfulness.  Being mindful and aware of our thoughts and feelings can 
help us remain focused on our values and remind us to move towards our goals. Actually, we can be 
mindful while doing pretty much anything.  For example, when you get dressed in the morning which 
foot do you put into your pants first? You probably don’t remember because it’s something you do 
without thinking about it. If you were to practice mindfulness while getting dressed, you would notice 
all sorts of things that you usually miss. You might notice the feel of the fabric of your pants as you 
pick them up and how your body adjusts to balance on one foot. You might notice how soft the fabric 
is against your skin or how the buttons on your shirt are really pretty. Imagine how much more you 
could experience if you actually paid attention to these things!   
 
This week: 
Practice being mindful when you are going through your daily routine.  Notice the thoughts that pop into 
your mind.  Say to yourself “I’m noticing my mind having this thought,” or “I notice that my body feels 
_______.”  The things you notice could be pleasant, like “I notice the sun feels nice and warm on my 

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face.”  Or they could be unpleasant, like “I notice my head starting to hurt.”  Whatever you notice, practice 
paying attention to what you are experiencing in the moment!   
And remember to practice your mindful breathing!   ☺  
 
Week Three 
Getting Some Perspective 
Now that you are several weeks into the program, what are your thoughts?  Feelings?  Have you noticed 
any differences in any areas of your life?   
This week, let’s review how we can be aware of our thoughts but not let them change how we act and 
what we do.  We spend so much time THINKING, that sometimes it’s easy to forget that our thoughts 
aren’t always right or in control. For example, if you have the thought “I’m a banana,” does that make you 
a banana? Of course not! Go ahead and try it: say to yourself “I’m a banana.”   Now look down…are you 
still you?  I’m guessing the answer is yes!  Just like having the thought “I can’t reach my goal” doesn’t 
mean that you actually can’t reach your goal. 
There are lots of ways we can practice having thoughts without acting on them. We can look at the 
thoughts in a different way or from a different perspective.  Here’s an example: 
Imagine that you are in the woods near a stream. As you’re sitting next to the stream enjoying the 
moment, thoughts may come up. You may think about a TV show that you watched last night or 
what you have to do at work or school tomorrow. Or you may start thinking about your pain.  You 
may think, “I’d like to stay here, but I am in pain.”  When these thoughts come up, they can pull 
you out of the current moment. If you’re thinking only about your pain then you’re not enjoying 
the calming nature setting.  
We might be able to get a different perspective by changing one word in the above thought.  Let’s 
change BUT to AND.  So now, we can say “I’d like to stay here, AND I am in pain.”  Does that 
change the meaning?  Just slightly, but yes!  Now you have a choice.  This may help you realize 
that you can be in pain AND continue to enjoy sitting by the stream.   
Other examples:  
(1) “I need to call my friend back, but I’m tired,” becomes “I need to call my friend back, AND 
I’m tired.” 
(2) “I’d like to read a book to my child, but I have a headache,” becomes “I’d like to read a book to 
my child, AND I have a headache.”   
In each case, you can choose what to do next based on your values, not based on the pain.   
 
This week: 
1) Look for opportunities this week to change a “but” to an “and”.  When you start to tell yourself 
you are unable to do something because of your pain, see if you can re-word that thought so you have 
a CHOICE.  “I’d like to do X, AND I am noticing some pain.”  Then make a choice about what to do 
next.  Whatever you choose, make sure the choice comes from your values, not your pain.   
2) Find a quiet space where you can practice this activity for five minutes.  When you are settled into 
a comfortable position, think about your pain and notice any feelings that come up.  Where in your 
body are they located?  Do you feel it in your head, your jaw, your shoulders?  Some people might 
feel a tightness in their chest, or butterflies in their stomach, or sweaty palms… Next, picture yourself 
breathing in and around that sensation in your body.  Take a few deep breaths.  Now picture yourself 
creating extra space in your body, opening up that area to make room for the feeling to move 
freely.  Finally, allow the feeling to be there even though you may not like it or want it.  Softly say to 
the feeling, “I notice you. You are my guest. You are welcome to stay here with me in this moment.”   
 

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Week Four  
Revisiting Goals 
 
Have you thought about the fact that, by signing up for this study, you are doing something to 
make positive changes in your life?  Traveling to the NIH, filling out all those forms, reading all 
these emails, having those video chat sessions – all of it is to help you move closer to your values.  
Not all people make that kind of effort, so take a minute to notice why you are doing all of this.   
Sometimes, when we start something new to improve our lives, we end up doing too much too 
soon.  We may set a goal for ourselves that ends up being too big.  For example, if one of your 
values is art, you may decide your goal is to paint a picture to hang on your wall.  If you already 
know how to pain, this may be fine.  But for someone who is just starting out, it may take a while 
to reach that goal.  In that case, the best thing to do may be to set some smaller goals along the 
way.  You might first set the goal of studying various art techniques.  You could look at art books, 
get some art supplies, even sign up for an art class.  Maybe you set one of those goals for each 
week.  When you have accomplished those goals, you will be much closer to reaching your long-
term goal of painting that picture!  
 
Remember the following steps for realistic goal-setting: 
1) If you lack skills, set new goals around learning them. 
2) If your goal is too big, break it down into small chunks. 
3) If you don’t have the things you need in order to reach your goal, think about how you can get 
them or whom you can ask for help.  
4) If you feel like you don’t have enough time to reach your goal, ask yourself what you are 
willing to give up in order to make time. 
5) If the goal is truly impossible, like because of health problems, lack of money, or other 
problems you cannot control, then set a different one that is more realistic.  
 
 
This week: 
Remember all the values you identified when you were at the NIH?  Take out your workbook and 
look at the ratings you gave yourself (page 7).  Using a different color ink (or different mark), rate 
yourself again on each of those values, thinking about the progress you have made so far.   
Now review the goals you set for yourself.  Have you reached any of them?  If not, think about 
how you can break the goal into smaller parts.  Write those down.  If you have reached one or 
more goals, check that off and then focus on the next one.  
 
We will be talking via video chat soon! 
 
Week Five 
Many Ways to Say Our Thoughts 
On page 2 of your workbook, you wrote down some thoughts that you sometimes notice about 
your pain.  Pick one of those thoughts now, and try the following ten steps: 
1. Say the thought out loud.   
2. Say it again in slow motion.   

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3. Say it as fast as you can.   
4. Say it standing on one foot.   
5. Say it jumping up and down.  
6. Say it in a high, squeaky voice.  
7. Say it in a low voice. 
8. Say it while trying not to move your lips.  
9. Sing it to the tune of Happy Birthday.   
10. Say it with a British accent.   
 
Do you notice anything about how you felt saying it in the beginning compared to how you felt at 
the end of those ten statements?  There is no right or wrong reaction. The point is just to notice 
what comes up as you go through the ten statements.   
This week:  
When you notice any thoughts that your mind hands you about your pain or your goals, try saying 
them out loud using some of the ten ideas above.  If you’re around other people, you can even do it 
inside your head.  Then notice how you feel afterwards.   
 
Week Six 
Writing About Your Values 
We are at week 6!  How did your assignment go last week?  Were you able to say any thoughts 
about your pain in a funny or different voice?  How did it go?  At the very least, did you laugh at 
how silly it might have seemed?  It can be a very different experience, reciting words or thoughts 
in that way!   
Here is a question for you: since you started this study, how much have you been thinking about 
your values?  Has it been more or less than before the study?  Have you noticed anything else in 
relation to thinking about your values?  Have you felt any differently?  There is no right or wrong 
answer.  It just may be something to consider.   
Interestingly, researchers have discovered that there are health benefits from writing about life 
goals and values.  So that is what your assignment is this week.  We can talk about how you did 
when we talk on video chat, but you do not have to share anything specific that you wrote about 
unless you want to!   
This week: 
Use a blank page in your workbook, a journal (if you have one), or just a spare piece of paper.  
Spend ten minutes writing about one of your values.  For example, try writing about:  
a) why the value is important to you 
b) things you have done that support this value  
c) things you would like to do to continue supporting the value 
d) anything else that comes to mind.   
 
If you find that you are still writing at the end of the 10 minutes, feel free to continue!  Remember, 
you don’t have to share what you have written with anyone if you don’t want to.  This is just for 
you.   
 
 
 
 

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Week Seven 
Commitment 
Do you realize that you only have a couple more weeks of this training program?  We talked before 
about one thing that can help us reach our goals - our commitment.  In other words, how sure are we 
that we are going to stick with the program? One way we can help our commitment stay strong is to 
get encouragement and support from other people.  Have you talked to other people about your goals 
and values?  Is anyone in your life cheering you on and helping you reach those goals? Is there 
anyone close to you who shares one of your values?    
 
There are a lot of ways that other people can show their support.  They might check in with you every 
week about your progress, or do a goal-related activity with you, or just listen when you need to talk.  
Having someone on your side can help you stay motivated and on track!   
 
This week: 
1) Think about a person who has supported you during this study so far.  This can be a friend, parent, 
brother or sister, other relative, boyfriend/girlfriend, spouse, coach, or teacher. If you have felt 
encouraged by their support, tell them that!  It can be something as simple as “Thank you for helping 
me work on these goals.”  Or you could do something nice for that person to show him or her how 
much their support means to you.   
If you could use a little extra support, ask for it gently.  You may say something like “Your support 
means a lot to me.  One way you could help me work towards my goal is to ___________.”  
2) As a bonus activity, you could then ask that person if there is anything you can do to help them on one of 
their goals!  If you are able to do something nice for that person, think about how good it feels to help the 
people we care for.  Does that relate to one of your values?   
 
 
Week Eight 
Don’t Stop Now! 
 
Congratulations – you are at the final week of the training program!   
   
This first part of the study is almost over.  Think about what you’ve accomplished during the past 8 
weeks. Have you reached any of your short-term goals? Have you been practicing mindfulness? How 
have these activities helped you in terms of the values that are important to you? Do you feel any 
different – physically or emotionally – than when you started the program?   
 
If you have been working towards your goals, you should take a moment to congratulate yourself on 
your hard work! And although you may have been able to check some goals off of your list, 
hopefully you want to keep living in support of your values. Just because you’re almost done with the 
ACT training program doesn’t mean we want you to stop what you’re doing!  Goals help us to work 
towards those values, but as long as we’re living, we’re never done living our values.   
 
So take some time to evaluate the progress you’ve made so far and give yourself credit for all your 
hard work. At the same time, keep striving to live your values, and think about what steps you can 
take to continue leading a more valued life.  
  

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This week: 
Consider what you can do in the coming weeks and months to help you live a valued life. You may 
be ready to set some new goals.  Think of a long-term goal and 3 short-term goals that you can work 
on next.  Remember, the most important thing about any goals that you set is that they should be 
related to one of the things that matter the most to you.   
Come up with your own long and short-term goals based on your values, and keep living those values every 
day!  Let’s discuss your ideas during our upcoming visit at the NIH.   
 
 

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9.23 APPENDIX S: ACCEPTANCE AND COMMITMENT THERAPY CORE COMPETENCY SELF-RATING FORM 
Below are listed a number of statements. Please rate how true each statement is for you when you use ACT, by circling 
a number next to it. Use the scale below to make your choice.  
 
1 
2 
3 
4 
5 
6 
7 
 
? 
never 
 true 
very 
seldom 
true 
seldom  
true 
sometimes  
true 
frequently  
true 
almost 
always 
true 
always  
true 
 
don’t 
know 
 
Core Competencies Involved in the Basic ACT Therapeutic Stance  
 
The basic psychological stance of the ACT therapist is an especially important factor in providing good 
treatment. This involves being able to make contact with the “space” from which ACT naturally flows, as well as 
modeling certain facets of psychological flexibility that we seek to impart to the client. Like many treatment traditions, 
ACT emphasizes the importance of therapist warmth and genuineness. This stance emerges quite naturally from the 
core understanding of human suffering from an ACT perspective. When we see our clients trapped by language, we 
see ourselves and the traps which generate our own pain. An “I and thou” perspective is the natural precipitant of this 
recognition. Collectively, the following attributes define the basic therapeutic stance of ACT. 
 
1 
The therapist realizes that he or she is in the same soup as the client and speaks to the 
client from an equal, vulnerable, genuine, and sharing point of view 
 
2 
The therapist models willingness to hold contradictory or difficult ideas, feelings, 
memories, and the like without needing to “resolve” them. 
 
3 
The therapist takes a compassionate and humanizing stance toward the client’s suffering 
and avoids criticism, judgment or taking a “one up” position 
 
4 
The therapist always brings the issue back to what the client’s experience is showing, 
and does not substitute his or her opinions for that genuine experience 
 
5 
The therapist does not argue with, lecture, coerce or even attempt to convince the client 
of anything. If you find yourself attempting to change a client’s mind, stop. You are not 
doing ACT. 
 
6 
The therapist does not explain the “meaning” of paradoxes or metaphors to develop 
“insight” 
 
7 
The therapist is willing to self disclose about personal issues when it makes a therapeutic 
point  
 
8 
The therapist avoids the use of “canned” ACT interventions. Interventions are responses 
to the particular client we are treating. 
 
9 
The therapist tailors interventions to fit the client’s language and immediate life 
experience 
 
10 
The therapist sequences and applies specific ACT interventions in response to client 
needs, and is ready to change course to fit those needs at any moment 
 

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11 
New metaphors, experiential exercises and behavioral tasks are allowed to emerge from 
the client’s own experience and context 
 
12 
ACT relevant processes are recognized in the moment and where appropriate are directly 
supported in the context of the therapeutic relationship 
 
 
Developing Acceptance and Willingness/Undermining Experiential Control 
 
13 
Therapist communicates that client is not broken, but is using unworkable strategies  
 
14 
Therapist helps client examine direct experience and detect emotional control strategies 
 
15 
Therapist helps client make direct contact with the paradoxical effect of emotional 
control strategies 
 
16 
Therapist actively uses concept of “workability” in clinical interactions 
 
17 
Therapist actively encourages client to experiment with stopping the struggle for 
emotional control and suggests willingness as an alternative. 
 
18 
Therapist uses shifts between control and willingness as an opportunity for the client to 
directly experience the contrast in vitality between the two strategies.  
 
19 
Therapist helps client investigate relationship between levels of willingness and sense of 
suffering willingness suffering diary; clean and dirty suffering) 
 
20 
Therapist helps client make experiential contact with the cost of being unwilling relative 
to valued life ends (Are you doing your values; listing out value, emotional control 
demand, cost, short term/long term costs and benefits) 
 
21 
Therapist helps client experience the qualities of willingness (a choice, a behavior, not 
wanting, same act regardless of how big the stakes) 
 
22 
Therapist uses exercises (jumping; cards in lap, eye contact) and metaphors (box full of 
stuff, Joe the bum) to help client contact willingness the action in the presence of 
difficult material 
 
23 
Therapists structures graded steps or exercises to practice willingness 
 
24 
Therapist models willingness in the therapeutic relationship 
 
25 
Therapist detects struggle in session and teaches the clients to do so 
 
 
 

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Undermining Cognitive Fusion 
 
26 
Therapist identifies client’s emotional, cognitive, behavioral or physical barriers to 
willingness 
 
27 
Therapist suggests that “attachment” to the literal meaning of these experiences makes 
willingness difficult to sustain  
 
28 
Therapist actively contrasts what the client’s “mind” says will work versus what the 
client’s experience says is working 
 
29 
Therapist uses language tools (get off our buts, both/and), metaphors (bubble on the 
head, two computers, monsters on the bus) and experiential exercises (tin can monster) 
to create a separation between the client and client’s conceptualized experience 
 
30 
Therapist uses various interventions to both reveal the flow of private experience and 
such experience is not “toxic” 
 
31 
Therapist works to get client to experiment with “having” these experiences, using 
willingness as a stance 
 
32 
Therapist uses various exercises, metaphors and behavioral tasks to reveal the “hidden” 
properties of language (milk, milk, milk; what are the numbers?) 
 
33 
Therapist helps client elucidate the client’s “story” and helps client make contact with 
the arbitrary nature of causal relationships within the story 
 
34 
Therapist helps client make contact with the evaluative and reason giving properties of 
the client’s story (no thing matters, good cup/bad cup) 
 
35 
Therapist detects “mindiness” (fusion) in session and teaches the client to detect it as 
well 
 
 
Getting in Contact with the Present Moment 
 
36 
Therapist can defuse from client content and direct attention to the moment 
 
37 
Therapist can bring his or her own feelings or thoughts in the moment into the 
therapeutic relationship 
 
38 
Therapist uses exercises to expand the clients sense of experience as an ongoing process 
 
39 
Therapists tracks content at multiple levels and emphasizes the present when it is useful 
 
40 
Therapist models coming back to the present moment 
 
41 
Therapist detects client drifting into past and future orientation and comes back to now 
 

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42 
Therapists teaches the client to do likewise 
 
 
Distinguishing the Conceptualized Self from Self-as-context 
 
43 
Therapist helps the client differentiate self-evaluations from the self that evaluates (thank 
your mind for that thought, calling a thought a thought, naming the event, pick an 
identity) 
 
44 
Therapist employs mindfulness exercises (the you the you call you; chessboard, soldiers 
in parade/leaves on the stream) to help client make contact with self-as-context 
 
45 
Therapist uses metaphors to highlight distinction between products and contents of 
consciousness versus consciousness (furniture in house, are you big enough to have you) 
 
46 
The therapist employs behavioral tasks (take your mind for a walk) to help client 
practice distinguishing private events from self 
 
47 
Therapist helps client understand the different qualities of self conceptualization, just 
noticing events and simple awareness 
 
 
Defining Valued Directions 
 
49 
Therapist helps client clarify valued life directions (values questionnaire, value 
clarification exercise, what do you want your life to stand for, funeral exercise) 
 
50 
Therapist helps client “go on record” as wanting to stand for valued life ends 
 
51 
Therapist puts his or her own therapy relevant values in the room and models their 
importance 
 
52 
Therapist teaches clients to distinguish between values and goals 
 
53 
Therapist distinguishes between outcomes and processes 
 
54 
Therapist respects client values and if unable to support them, finds referral or other 
alternatives 
 
 
Building Patterns of Committed Action 
 
55 
Therapist helps client identify valued life goals and build an action plan 
 
56 
Therapist encourages client to “have” barriers and make and keep commitments 
 

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57 
Therapist uses exercise and non traditional uses of language to reveal hidden sources of 
interference to committed actions (fish hook metaphor, forgiveness, who would be made 
right, how is your story every going to handle you being healthy) 
 
58 
Therapist encourages client to take small steps and to look at the quality of committed 
action 
 
59 
Therapist keep clients focused on larger and larger patterns of action 
 
60 
Therapist integrates slips or relapses into the experiential base for future effective action 
 
 
 
 

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9.25 APPENDIX T: TREATMENT FIDELITY CHECKLIST 
Session 1 
 
Technique/Concept 
Presented/Discussed 
Creative Hopeless – discussion of how pain impacts the patient’s life, 
what they have avoided or given up 
 
Mindfulness exercise(s) in session with follow-up discussion of 
patient’s perceptions, reactions 
 
Avoidance versus Acceptance – with discussion of how willingness to 
experience pain is essential for living a valued life 
 
Use of metaphor/experiential exercises (e.g., Tug-of-war, Index card 
exercise) to demonstrate concepts 
 
Self-compassion – imagery exercise and/or discussion of how lack of 
self-compassion can negatively impact emotional well-being 
 
Out-of-session practice – Assign exercises to work on before Session 2 
 
 
 
Session 2 
 
Technique/Concept 
Presented/Discussed 
Values Assessment – help patient identify values; do values imagery 
exercise 
 
Completion of Values Rating Form 
 
Values vs. Goals 
 
Completion of Goal-setting Form for at least two values 
 
Dealing with Obstacles – choice point/swamp metaphor 
 
Enlisting support – discussion of how important others can support their 
pursuit of valued living 
 
Review workbook for at-home practice 
 
 
 
 
 
 
 

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9.27 APPENDIX U:  ACT MANUAL 
 
SESSION ONE  
Overview of sessions   
• This treatment is for people who have NF1 and PNs, and chronic pain.   
• Today’s session: about two hours, with a break about half way through 
• We will be talking about how pain impacts your life, about some of the main 
concepts in Acceptance and Commitment Training, or ACT, and about how these 
can be useful for people with chronic pain. 
 
Confidentiality 
• Psychologists are bound by limits to confidentiality; by law, we have to report if we 
think you are a danger to yourself or someone else, or if we learn about a situation 
involving child abuse.  
2 minutes 
 
Define ACT 
• Purpose of ACT is to help people live a full and meaningful life with the pain that 
goes with it.   
• You may not be able to change your pain, but you can change your relationship 
with your pain.  
• There are a number of central concepts in ACT, and over these two sessions we’ll 
go through them all.   
• Many things we’ll talk about and ideas I’ll ask you to consider might seem strange, 
and that’s okay. I’m not asking you to believe anything I say.  I’m just asking you 
to participate fully and see what happens.   
3 minutes 
 
How does pain impact your life? 
• How does pain impact your life?  What areas of your life would be different if you 
didn’t have pain?  Work? School? Relationships? Others? 
• What thoughts come up when you think about your worst pain?  [Workbook pg 2] 
• What have you tried to get rid of your pain?  How do you try to avoid pain? What 
has worked in the long term? [Establish creative hopelessness.] [Workbook pg 2] 
10 min 
Our minds: helpful or harmful? 
• Basic functions of our minds.  They help us think, reason, feel, behave a certain 
way, etc. When we talk about our thoughts, we are going to refer to our “minds” as 
being where our thoughts come from.  Sometimes our minds are helpful, and 
sometimes they are not.  Our minds have evolved to try to tell us when there’s 
danger, they tell you if something is good or bad for you, and they’ll talk about the 
same things over and over.   
• When our minds are not helpful: What does your mind say to you if you make a 
mistake? [Discuss how things our minds say can make us feel or act a certain way.] 
2 minutes 
 
Mindfulness  
3 minutes 

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• Mindfulness means “Noticing what’s going on around you and inside you with 
flexibility, openness, and curiosity.” 
• Discuss impact of not being mindful or aware of what we do or feel in the moment.   
• Examples of “mindlessness” – auto-pilot, sleepwalking…Finishing a meal and 
realizing that you barely remember eating it, getting to the end of a paragraph and 
not remembering anything you read.  Sometimes your thoughts will go back to the 
past or something that may happen in the future, and so you end up missing out on 
the present. 
• Why is mindfulness important?  It helps us be more aware of everything going on 
within and around us so that when we react, we do so with clarity and purpose. 
• How does someone become more mindful? It’s as simple as breathing… 
 
Mindfulness Exercise   
• Part 1: Mindfulness of Breath – notice your breathing as you inhale and exhale.  
Don’t try to change it, just remain aware.  If you get distracted, gently bring your 
focus back to your breath.  (Purpose is not to relax, just to notice).   
• Part 2: Notice any thoughts about this study, about what you’re missing at home or 
work, anything else that comes up.  Visualize letting those thoughts sit with you in 
the room while you’re here, but not letting them take over.  Connect with what 
value led you to be here.    
• Brief discussion of person’s experience. 
10 minutes 
 
Mindfulness At Home (workbook page 3) 
• Morning Routine 
• Mindfulness of Domestic Chores 
• Mindfulness of Pleasant Activities 
5 minutes 
 
Acknowledgement (the opposite of avoidance) 
• Acknowledging one’s pain means having an attitude that your situation is real and 
believable without trying to change what cannot be changed.   
• Acknowledge thoughts about pain without judging them, reacting impulsively 
• Acceptance of your pain means that you believe it to be real and true, it does not 
mean you’re giving up or that you like it. Wanting to get rid of the pain is natural, 
but that’s different from actively struggling against it.  
• Tug-of-war metaphor – use rope to exemplify how we can pull against something 
for so long, but if we drop the rope we get out of the struggle easily.   
10 minutes 
 
Acceptance Exercise: Expansion 
• Expansion means giving yourself space to experience pain (physical or emotional 
pain).   
(1) Observe → What are the feelings/physical sensations that arise when you think 
about your worst pain?  Notice them, where in your body is it located? 
(2) Breathe → Visualize yourself breathing into and around the sensation.  
(3) Create space → Imagine yourself creating extra space within your body, opening up 
to make room for the sensation to move freely. 
(4) Allow → Allow the sensation to be there even though you don’t like or want it.   
 
10 minutes 
 
 

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Practice this now.   
Discuss patient’s experience: what was it like to not resist the pain?  If the person says 
it was strange or difficult, reinforce the idea that they stuck with despite those 
thoughts… 
Relationship between thoughts, feelings, behaviors (workbook page 4) 
• Relationship between pain, thoughts/feelings, and behaviors: they each can impact 
the others, can become a vicious cycle.   
• Which of these three things do we have the most control over?   
• Chocolate Cake Metaphor - instruct patient to not think of chocolate cake for 10 
seconds.  [Illustrates lack of control over thoughts.] 
• Electric shock exercise – imagine you are hooked up to a machine that will deliver 
a painful shock if you feel any anxiety in the next minute. [Illustrates lack of 
control over feelings.]   So our best bet is our behavior. 
7 minutes 
 
 
Break 
5 minutes 
Defusion  
• Another principle in ACT relates to what we call “holding thoughts lightly”.  This 
means stepping back and separating from our thoughts, images, and memories; 
seeing our thoughts for what they are – just words or pictures. Just because we have 
thoughts does not make them true.  Some people who live with chronic pain have 
thoughts like “When I have pain I have to _________.”  [Ask patient to fill in the 
blank.]  “Hold them lightly instead of clutching them tightly”.   
• Card Exercise - Write down key phrases the patient uses to describe his/her pain on 
index cards.  First talk about how pain can feel like it’s right in front of your face.  
What’s the problem with this?  Can we have a conversation?   
• Next, toss the index cards toward the patient first instructing them to not let any 
land on them, then instructing them to let them land where they may.  Notice the 
difference in the energy expended when you are fighting to keep your pain away 
versus accepting it.   
• Examples of other metaphors - Notice a thought, picture it, then put it on a leaf 
floating by on a stream.  Words scrolling by on a computer screen.  Cars passing by 
outside your window.  Which one does the patient like best?  (workbook page 5) 
5 minutes 
 
Distancing 
• Choose one thought the patient often has about their pain.  Practice adjusting the 
content as follows: 
      I can’t stand this pain. 
      I’m having the thought I can’t stand this pain. 
      I notice my mind having the thought I can’t stand this pain. 
• Physically distancing oneself from “pain” – have person write “pain” (or a thought 
about their pain) on a piece of paper, then first stand on it, then take one step back, 
then another, noticing their experience.  Discuss.   
5 minutes 
Pain Versus Values  
15 minutes 

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• Are there times when your pain gets in the way of living according to your values? 
[discuss examples from client’s life]  
• Examples: (1) It is important to spend time with my friends, but there are times 
when I stay home or avoid group activities because of my pain.  (2) My 
education/career is important, but I sometimes don’t go to class/work because I am 
in pain.   
• Show picture of two identical circles – one surrounded by small circles, one by 
large circles.  Discuss idea that the first one looks bigger.  Those center circles are 
to represent pain.  What fills the outer circles…values.  Fill in the circles together.  
Why do those outer circles get so small sometimes?     
• A → B → C    Review ABC model where A = activating event, B = behavior, C = 
consequence.  Discuss examples where consequences are missing out on valued 
activities.   
Body Scan.   
• Review each part of the body, starting with feet, then legs, abdomen, chest, arms, 
neck, head. Ask patient to notice sensations in each body part without judging.     
10 minutes 
 
Slowing Things Down 
• Discuss slowing down the interaction between A and B.  Creating space here 
through mindfulness, acknowledging…[Give examples] 
5 minutes 
Self-compassion  
• Acknowledging that living with chronic pain is not easy; sometimes others don’t 
understand, can be unkind, sometimes our minds are unkind as well.   
• What are some examples of things our minds say to us that are unkind?  When our 
minds tell us these things, how do we feel inside?  When have others made things 
more difficult? 
• Imagery exercise: Imagine yourself as a young child of 5 or 6 years old.  Imagine 
the child asking you for what he/she needed then.  If you had one minute to tell 
them something helpful, what would it be?  Imagine giving the child compassion.  
[Discussion.] 
10 minutes 
 
Out-of-Session Assignments 
1) Talk a walk.  Walk around the neighborhood (or clinical center, Inn) with the goal 
being just to talk a walk.  Focus on internal sensations (your feet as they touch the 
ground, the way your arms swing back and forth) and external stimuli (sounds of birds 
chirping or traffic, breezes).  Avoid talking to others.   
2) Mindfulness exercise.  Do a body scan or mindful breathing for 5 minutes.   
3 minutes 
 

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SESSION TWO  
Checking In  
Ask about experiences doing the Mindfulness exercises last night.  Thoughts about 
Session 1.   
5 minutes 
Values Assessment 
• We need our minds to help us do some things, but other times it is important to 
use something else to guide us:  VALUES – the things that are most important to 
us, what we want our life to be about. ACT is based on the idea that the key to 
leading a fulfilling life is defining your values and acting on them. 
• Discuss question: What are you willing to have in order to live a valued life? 
10 minutes 
 
What Do You Want Your Life To Stand For exercise (can be brief or longer 
depending on how well the person is in touch with values) 
• Imagine you are at your next milestone birthday party. You are listening to 
people get up and talk about you, the kind of person you are, your parents, your 
siblings, your friends, your children, etc.  What would you like those people to 
say about you?  Imagine them saying exactly what you would most want them to 
say.  [If participants have a hard time thinking of values, ask them to name 
someone they admire and talk about the particular qualities s/he admires.] 
5 minutes 
Values Compass 
• Workbook page 7: Discuss areas where you might have certain values.  For 
example, in the “community” area, you might have values related to a certain 
group you’re involved with in the community (a charity or club at school that 
does community service).  Trainer can gently encourage a focus on the areas 
most impacted by pain, if patient is ready for that.   
• Make distinction between values and goals.   
• Rate each one (1-10) on how close patient is living in accordance with those 
values. 
• Importance of moving just one point in the valued direction.  
15 minutes 
 
 
 
Goal-setting  
• Discussion of Values vs. Goals 
• Introduce Goals Form and have patient start filling it out. [Workbook page 9] 
• Complete form together for at least two values. 
20 minutes 
 
 
Demons on the Boat 
• As you’ve thought about your goals, one thing you might notice (or may notice 
soon) is that your minds might start up again, telling you all kinds of not-helpful 
things, like “You can’t do that!” or “You’ve tried that before and it never 
works.”   
• When this happens, it can be helpful to think about something we call “Demons 
on the Boat.”  Explain metaphor – those thoughts sometimes come up right when 
we’re making progress, but are we willing to have them and still move towards 
our goal?   
5 minutes 
 

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Break 
5 minutes 
How to Deal With the Obstacles 
• Swamp metaphor/Choice point guided exercise: You start out towards your goal 
of reaching a desired place but soon find yourself having to trudge through a 
muddy swamp to get there.  What do you do? 
• Imagine it both ways…turning around and going home, or moving forward. 
What feelings and thoughts show up?  [Discuss reactions] 
• Review Facing Barriers exercise [workbook page 14] 
10 minutes 
Enlisting Support and Addressing Conflicts  
• How to deal with conflicts with other people in our lives about practicing ACT 
techniques at home; how to enlist their support.   
• Sample script [workbook page 15] 
• Ultimately we may have to accept others’ lack of acceptance. 
5 minutes 
Generalizing Techniques 
• How patients can apply these techniques to other areas of their life, other 
problems related to their NF (learning disabilities, visible tumors, etc) 
• Ask patient to share other areas of his/her life besides pain that cause challenges 
or difficulties – start with other aspects of NF, but anything is okay.   
• Help them come up with ACT techniques that are applicable.   
15 minutes 
 
 
Worries Moving Forward 
• Ask participants to name any worries they might be having about how they will 
do once they get back home and into their normal routine. 
• On index card: Write down fears and take the card with them.  Emphasize that 
they can move forward even while having doubts.  Also, they are not committing 
to be successful in every attempt they make.  But each time they do not 
accomplish a goal, they need to re-commit to try again.   
5 minutes 
 
 
Final Mindfulness Exercise  
• With each breath in, visualize breathing in compassion for yourself as you make 
space for the awareness that you will falter, you will trip up, and run into 
obstacles when you try to apply these techniques at home. Your breath is taking 
in an acceptance of that awareness and a gentle reminder for you to be kind and 
compassionate to yourself when that happens. With each breath out, breathe out 
kindness and warmth to others that are with you on your journey, your partners, 
friends, families, teachers, and breathe out an awareness that they will mess up 
as well, so with each exhale, you’re noticing the need to be compassionate 
towards them when that happens.  
5 minutes 
 
Wrap-up 
• Workbooks have additional exercises to continue working at home.  
• Discuss weekly emails again and biweekly video chat sessions. 
5 minutes 
 
 
 

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9.28 APPENDIX V:  RECRUITMENT E-MAILS 
9.28.1 NCI Patient E-mail 
Dear Sir or Madam: 
 
We are emailing you because you indicated on the CTF Registry that you are willing to be notified about 
research studies.  There is a new study at the National Cancer Institute evaluating an intervention to help 
people cope with chronic pain related to plexiform neurofibroma tumors.  The intervention is called 
Acceptance and Commitment Training, or ACT.  It has been found to be effective in many studies of people 
with pain who have other medical conditions.  A small study by our group suggests that it may be helpful for 
people with NF1 as well because it decreased how much pain interfered with people’s daily lives.   
 
For this new study, people will be asked to come to the NIH for a 2-day visit.  During this visit, they will fill 
out some questionnaires that ask about things like pain severity and emotional well-being.  They also will get 
an electrocardiogram (ECG), which is a painless procedure that monitors heart rate.  Next, we will randomly 
select (like flipping a coin) half of the people to do the ACT training right away.  The other half will be put 
on a wait list for two months, and then return to the NIH to do the training.   
 
There are three parts to the training.  First, you will participate in two 2-hour sessions with an ACT trainer at 
the NIH during which you will learn new ways of coping with pain.  Second, you will receive weekly emails 
for 8 weeks, each about ways you can work on ACT techniques at home.  Third, you will have three video 
chat sessions (such as Skype, done on your home computer at week 2, week 4, and week 6) with your ACT 
trainer.   
 
At the end of the 8-week training, we will ask everyone to return to the NIH to complete questionnaires 
again and get another ECG.  Six months later, we will ask you to complete the questionnaires one last time 
from your home computer.   
 
To be eligible, you must be between 16 and 59 years of age, have one or more plexiform neurofibromas, and 
have chronic pain for at least the past three months. You also must be able to read and speak English, and 
have regular access to a computer with internet access.  Individuals ages 16 and 17 years must have a parent 
or guardian give permission for their participation.   
 
The NIH will offer some reimbursement for travel and expenses for people who live more than 50 miles 
away. Also, all participants will receive a small monetary gift to thank you for your time each time you 
complete a set of questionnaires (3 to 4 times total).   
 
To learn more about the study, please contact Associate Investigator Taryn Allen, PhD (240-760-6001, 
taryn.allen@nih.gov) or the study’s Principal Investigator, Staci Martin, PhD., (240-760-6025, 
martins@mail.nih.gov).  We will be able to tell you more about the study requirements and find out if you 
are eligible.   
 
 
 

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9.28.2 Recruitment E-mail CTF Registry 
Dear Sir or Madam: 
 
We are emailing you because you indicated on the CTF Registry that you are willing to be notified about 
research studies.  There is a new study at the National Cancer Institute evaluating an intervention to help 
people cope with chronic pain related to plexiform neurofibroma tumors.  The intervention is called 
Acceptance and Commitment Training, or ACT.  It has been found to be effective in many studies of people 
with pain who have other medical conditions.  A small study by our group suggests that it may be helpful for 
people with NF1 as well because it decreased how much pain interfered with people’s daily lives.   
 
For this new study, people will be asked to come to the NIH for a 2-day visit.  During this visit, they will fill 
out some questionnaires that ask about things like pain severity and emotional well-being.  They also will get 
an electrocardiogram (ECG), which is a painless procedure that monitors heart rate.  Next, we will randomly 
select (like flipping a coin) half of the people to do the ACT training right away.  The other half will be put 
on a wait list for two months, and then return to the NIH to do the training.   
 
There are three parts to the training.  First, you will participate in two 2-hour sessions with an ACT trainer at 
the NIH during which you will learn new ways of coping with pain.  Second, you will receive weekly emails 
for 8 weeks, each about ways you can work on ACT techniques at home.  Third, you will have three video 
chat sessions (done on your home computer at week 2, week 4, and week 6) with your ACT trainer.   
 
At the end of the 8-week training, we will ask everyone to return to the NIH to complete questionnaires 
again and get another ECG.  Three months later, we will ask you to complete the questionnaires one last time 
from your home computer.   
 
To be eligible, you must be between 16 and 59 years of age, have one or more plexiform neurofibromas, and 
have chronic pain for at least the past three months. You also must be able to read and speak English, and 
have regular access to a computer with internet access.  Individuals ages 16 and 17 years must have a parent 
or guardian give permission for their participation.   
 
The NIH will offer some reimbursement for travel and expenses for people who live more than 50 miles 
away. Also, everyone will receive a small monetary gift to thank you for your time each time you complete a 
set of questionnaires.   
 
To learn more about the study, please contact Taryn Allen, PhD, at 240-760-6001 (taryn.allen@nih.gov) or 
the study’s Principal Investigator, Staci Martin Peron, PhD., at 240-760-6025, or email her at 
martins@mail.nih.gov.  We will be able to tell you more about the study requirements and find out if you are 
eligible.   
 
 
 

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9.29 APPENDIX W:  RECRUITMENT FLYER 
Coping with Pain: 
an ACTive Approach 
 
 
 
✓ Do you have NF1 and one or more plexiform neurofibromas?   
✓ Do you have pain that has lasted three months or more?   
✓ Are you between the ages of 16 and 59 years?   
 
If you answered yes to all these questions, you may be eligible for a new study at the 
National Cancer Institute in Bethesda, Maryland.   
 
The study is evaluating an intervention called Acceptance and Commitment Training, or 
ACT, which has been found effective in other medical populations for decreasing how much 
pain interferes with daily life.   
Funding is available to cover travel and lodging costs, and participants are paid to thank them 
for their time.   
To learn more about the study, please contact: 
Dr. Taryn Allen   
 
 
or  
 
Dr. Staci Martin 
240-760-6001  
 
 
 
 
 
240-760-6025 
 
 
 
taryn.allen@nih.gov  
 
 
 
 
martins@mail.nih.gov 
 
 
 
 
ACT for Pain 
Dr. Staci Martin  
240-760-6025 
ACT for Pain 
Dr. Staci Martin  
240-760-6025 
ACT for Pain 
Dr. Staci Martin  
240-760-6025 
ACT for Pain 
Dr. Staci Martin  
240-760-6025 
ACT for Pain 
Dr. Staci Martin  
240-760-6025 
ACT for Pain 
Dr. Staci Martin  
240-760-6025 
ACT for Pain 
Dr. Staci Martin  
240-760-6025 
ACT for Pain 
Dr. Staci Martin  
240-760-6025