Efficacy and Mechanistic Testing of a Self-Management Intervention for Managing Chronic Pain With Cancer Survivors
Phase: NA
Conditions: Chronic Pain
Sponsor: University of Washington

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Last Approved by Human Protections Review Committee: January 28, 2019, v. 3.0 
 
 
 
 
 
 
 
 
 
Official Title: 
Hypnosis for Chronic Pain Relief in Cancer Survivors 
NCT number: 
03867760 
Document Type:  
Study Protocol and Statistical Analysis Plan 
Date of the 
Document: 
January 28, 2019 
 
 

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Last Approved by Human Protections Review Committee: January 28, 2019, v. 3.0 
 
 
RESEARCH PROTOCOL 
Methods and Design 
Design. The study design is a two-arm RCT. The study uses an expanded protocol from the pilot RCT. 
The primary outcome (pain intensity) and secondary outcomes (pain interference, anxiety, depression, fatigue, 
and sleep disturbance) will be assessed at baseline, mid-study, and end of study. In addition, pain intensity 
and anxiety will be assessed daily. Participants will be randomly assigned to the RHI or an attention control 
condition (relaxation recording). Furthermore, an extreme phenotype approach will be taken to study brain 
states as a mechanism for hypnosis-induced pain reduction. Five participants from each group who score low 
(score = 0 - 1)1 on the hypnotic suggestibility scale and 5 participants from each group who score high (score = 
4 - 5)1 will be invited to undergo qEEG measurement.  
Sample and Settings. A convenience sample of 100 cancer survivors with chronic pain will be recruited 
from the Seattle Cancer Care Alliance (SCCA) Survivorship Clinic. SCCA is a National Cancer Institute-
designated comprehensive cancer center where more than 6,000 patients with cancer received treatment last 
year. In 2016, 194 patients were seen at the Survivorship Clinic (based on chronic pain prevalence estimate of 
39%, 76 patients with pain). 
Power Analysis. Table 1 shows the minimal detectable      Table 1. Minimal Detectable Change in RHI Group 
change in the mean of the RHI group that can be detected           For N=100 (50/group), 80% power, alpha = 0.05, two-sided 
given a total sample of 100 participants and 80% power, 
based on standard deviations observed in our prior research.  
Participant Inclusion and Exclusion Criteria. Participant 
inclusion criteria are: (1) self-reporting moderate or higher 
pain on average during the last week (> 3 on a 0-10 pain intensity numeric scale), (2) self-reporting chronic 
pain related to cancer or its treatment, (3) completed active cancer treatment other than maintenance therapy, 
(4) being > 18 years of age, (5) functional fluency in English, and (6) mentally and physically able to participate 
and complete surveys. Participant exclusion criteria are: (1) a history of seizure disorder and (2) a significant 
brain injury or skull defect. Both exclusion criterion may impact qEEG measurement. We will not exclude 
potential participants based on use of pain medication, rather we will collect this information (drug, dose) and 
control for it in the data analysis.   
Participant Recruitment. Staff at the SCCA Survivorship Clinic will screen Survivor Surveys completed by 
patients prior to their initial clinic visit from the past 2 years and during the study to identify patients who meet 
the pain intensity inclusion criteria. Names and contact information for patients will be given to the research 
team who will mail an information letter describing the study. The letter will include an opt-out postcard to be 
returned if the patient is not interested in being contacted by telephone about the study. Two weeks after the 
letters are mailed, patients will be contacted by telephone to further screen for eligibility and describe the study. 
If the patient is eligible and interested in participating, verbal and written consent to participate will be obtained. 
A study visit will be scheduled at the UW Health Sciences Center (HSC) for completion of the Stanford 
Hypnotic Clinical Scale and assignment of the intervention. The consent form and baseline questionnaires will 
be mailed to the participant to sign and complete respectively and return at the Week 0 (baseline) study visit.  
Group Assignment. A SPSS randomization program will yield group assignments which will be placed in 
opaque, sequentially numbered sealed envelopes. Once the participant returns the completed baseline 
questionnaires and completes the in-person hypnotic clinical measure at the Week 0 study visit, the 
appropriate envelope will be opened and the participant will be notified of his/her group assignment. Based on 
their high or low hypnotic suggestibility score, eligible participants will be invited to participate in the qEEG 
study arm. 
Intervention/Independent Variables. Hypnosis Intervention. The RHI consists of four 12- 18-minute 
digital recordings that I will make using standardized hypnosis scripts for pain reduction2 and upload to a MP3 
player. The scripts were developed for patients with chronic pain and tested by a psychologist who is an expert 
in hypnosis research (Jensen, co-mentor). Participants will listen to the recordings daily for 28 days in the 
prescribed order (4 recordings for 3 days each, and then any recording for the remaining 16 days). Selected 
recordings will be noted by the participant on the Daily Diary. The script includes an induction, suggestions for 
how to access inner resources and manage pain, and post-hypnotic suggestions for permanence of hypnosis 
Pain Score Standard Deviation  
Small SD (1.0) 
Expected SD (1.5) 
Large SD (2.0) 
-0.57 
-0.85 
-1.13 

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benefits and self-hypnosis practice. Attention Control. The relaxation recordings will be uploaded to a MP3 
player. Four different 12- 18-minute recordings of the selected genre will be listened to daily for 28 days (same 
prescribed order as the RHI).  
 
Table 2a. Instruments.  
Aim 
Study Measures 
Variable Measured 
Week 
0  
Daily 
Week 
2 
Week 
4 
1 
*PROMIS 29 v. 1.0 
29-item questionnaire, Cronbach’s α 0.92-0.97.3 
Pain interference, anxiety, 
depression, fatigue, sleep  
X 
 
X 
X 
1 
*PROMIS v.1.0-Pain Intensity 3a 
3-item questionnaire, Cronbach’s α 0.92-0.97.3  
Pain intensity 
X 
 
X 
X 
2 
*PROMIS Self-Efficacy for Managing 
Symptoms 
Self-Efficacy 
X 
 
 
X 
3 
qEEG 
Brain activity/state 
X 
 
X 
X 
* National Institute of Nursing Research (NINR) Common Data Elements  
 
Table 2b. Instruments.  
Aim 
Study Measures 
Variable Measured 
Week 
0  
Daily 
Week 
2  
Week 
4 
1 
Daily Diary  
9-item questionnaire completed at bedtime, 
feasibility of participants completing it on a daily 
basis was established in pilot study. 
Pain intensity, anxiety, and use 
of RHI or relaxation recording 
(including which recording 
used) 
 
X 
 
 
2 
Stanford Hypnotic Clinical Scale for Adults 
 5-item scale, 20 minutes to administer, product-
moment correlation between total score and 
Stanford Hypnotic Scale C total score 0.72.1 
Hypnotic suggestibility  
X 
 
 
 
2 
Tellegen Absorption Scale 
34-item multi-dimensional scale,4 test-retest 
reliability 0.85.5 
Absorption (Imaginative 
involvement, tendency to 
become mentally absorbed) 
X 
 
 
 
2 
Credibility/Expectancy Questionnaire 
4-item questionnaire, test–retest 0.62-0.78, 
Cronbach’s α 0.84-0.85.6 
Treatment outcome expectancy 
X 
 
 
 
1 
Demographic Questionnaire 
15-item questionnaire. 
Socio-demographics; cancer & 
treatment, and pain history; co-  
morbidities; pain interventions 
X 
 
 
 
3 
Structured Interviews 
Each interview is anticipated to last 20 minutes and 
will be audio-recorded.  
Barriers and facilitators 
associated with undergoing 
qEEG measurement; how 
intervention works 
 
 
 
X 
 
Data Collection Schedule and Procedures. Study Enrollment. The research assistant (RA) will contact 
potential study participants by telephone to screen, obtain verbal consent, and schedule the Week 0 study visit 
at the UW HSC. Baseline questionnaires and consent form will be mailed to the participant with instructions to 
complete 1-2 days before the Week 0 study visit.  
Week 0 Study Visit. The RA will meet with the participant to (1) collect completed questionnaires and 
signed consent form; (2) administer the Stanford Hypnotic Clinical Scale; (3) share group assignment; (4) 
provide teaching about the RHI or relaxation recording, and participant study responsibilities; (5) administer the 
Credibility/Expectancy Questionnaire; and (6) inform participant if they are eligible for the qEEG measurement. 
Participants who are ineligible for the qEEG measurement (or eligible but not interested in participating) will 
begin using the assigned intervention at home on the same day as the Week 0 visit. The RA will schedule 
telephone calls with ALL participants to complete study measures at Week 2 (within 5 days of using the 
assigned intervention for 14 days), and Week 4 (within 5 days of using the assigned intervention for 28 days). 
Structured interviews with the RA also will be conducted by telephone. Participants will be reminded to return 
the Daily Diary in the provided pre-posted return envelope. Participants in the qEEG study arm will undergo the 
first qEEG at the Week 0 visit and begin using the assigned intervention at this time. All qEEG measurements 

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will take place at the UW Integrative Brain Imaging Center (IBIC). Week 2 and Week 4 qEEGs will be 
scheduled at the Week 0 visit and will take place within one day of completing study measures.  
 
qEEG Protocol: The participant will complete a 0-10 pain intensity numeric scale pre- and post-qEEG. 
During the qEEG, the intervention group participant will listen to the RHI and the attention control group 
participant will listen to the relaxation recording via the MP3 player (Table 3). The EEG technologist will fit an 
electrode cap with premeasured sites using the international 10/20 system7 to the participant’s head and the 
participant’s scalp and will prep the earlobes with Nuprep (Weaver and Company, Aurora, CO, USA). The 
electrode sites will be filled with Electro-Gel (Electro-Cap International, Eaton, OH, USA) and prepped to 
ensure impedance values between 3 and 5 Kohms between each electrode site and each ear individually. The 
signals will be amplified using a bandpass of 0.53-70 Hz and sampled at the rate of 250 Hz. for 10 minutes 
(eyes closed) with an EGI Geodesic EEG System 300 using 128-channel HydroCel Nets. Participants will be 
monitored throughout the recording to ensure that they remain awake. 
Per the UW IBC, raw recordings will be band-pass filtered between 0.5-100 Hz, and exported to Matlab 
(MathWorks, Natick, MA, USA) and then remontaged to the average reference montage. Plotted data will be 
inspected for potential artifacts (e.g., evidence of eye blinks, eye movements, body movements) and entire 
epochs will be removed if one or more channels exhibit presence of artifact. qEEG spectrum will be calculated 
from the first 2 minutes of artifact-free data with fast Fourier transform using 4-second epochs with 1/32 
seconds of overlapping window advancement factor. The relative EEG power will be computed for each of five 
bandwidths (delta, 1.5-4 Hz; theta, 4-8 Hz; alpha, 8-13 Hz; beta, 13-30 Hz; gamma, 30-55 Hz), and the power 
estimates will be used for all subsequent analyses by our research team. Relative power measures show a 
closer correspondence to underlying cortical activity than does absolute power.8                   
    All participants will 
Table 3. qEEG Measurement Timeline              
receive $50 for their 
participation, which will be 
distributed as follows: 
after return of the baseline 
questionnaires ($25) and diary ($25). Participants also will be given $25 to pay for parking and gas, or for 
public transportation for the visit to the UW HSC. The 20 participants undergoing qEEG will receive an 
additional $50 after completing each qEEG for a total of $150. They also will be given $25 to pay for parking 
and gas, or for public transportation to the UW IBIC for two visits ($50). Data will be managed using REDCap 
(Research Electronic Data Capture).9 The RA will be responsible for data entry and I will verify its accuracy.  
Data Analysis.  Aim 1:  Does the RHI work? Evaluate the efficacy of RHI in reducing self-reported pain 
intensity (primary outcome) and pain interference, anxiety , depression, fatigue, and sleep disturbance 
(secondary outcomes) at 4 weeks compared to the attention control condition (relaxation recording). We will 
use ANCOVA controlling for baseline scores and co-variates including pharmacologic treatments to test 
whether mean pain intensity at week 4 differs between the RHI and relaxation groups. The same analysis will 
be done for the secondary outcomes.  In addition, we will graphically describe trajectories of daily pain and 
anxiety at Weeks 0, 2, and 4, based on the Daily Diary for pain intensity and anxiety in the RHI and relaxation 
groups. This approach will allow us to understand whether an increased dose of the intervention (i.e., 4 weeks 
vs. 2) is necessary to achieved significant reduction in pain intensity.   
Aim 2: For whom does the RHI work? Examine if psychological factors (hypnotic suggestibility, mental 
absorption, treatment outcome expectancy) moderate the relationship between RHI and pain intensity at 
weeks 0, 2, and 4. The following multiple regression model will be estimated: 
PAINweek2 = Painweek0 + PSYweek0 + RHI + PSYweek0xRHI, where moderator effects will be indicated by the 
interaction term PSYweek0xRHI. We will measure Cohen’s d for each of the levels of the moderator and 
compare them to determine the moderator effect. The resulting effect size will be used to estimate the sample 
size in a larger follow-up study (e.g., R01). 
Aim 3:  How does the RHI work? Compare brain states as measured by qEEG in cancer survivors with 
chronic pain receiving the RHI relative to the attention control condition (relaxation recording) at weeks 0, 2, 
and 4. We will use multiple regression models controlling for baseline scores and co-variates (e.g., medication 
use) to compare the change in theta activity from pre-session to during session between RHI and relaxation 
groups. We will also compare the change in theta activity from pre-session to post-session between groups. 
This will be replicated for all 3 time points: Weeks 0, 2, and 4. Replication allows us to assess if theta activity 
 
                Pre-Session                    During Session                Post-Session 
Week 0  
10 minutes eyes closed 
13 minutes RHI or relaxation 10 minutes eyes closed 
Week 2  
10 minutes eyes closed 
13 minutes RHI or relaxation 10 minutes eyes closed 
Week 4  
10 minutes eyes closed 
13 minutes RHI or relaxation 10 minutes eyes closed   

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Last Approved by Human Protections Review Committee: January 28, 2019, v. 3.0 
 
changes during the study period. We will also explore other bandwidths (e.g., alpha, beta, delta, gamma) in our 
analysis. Medium or larger effect sizes for changes in bandwidth activity will be used to indicate that more 
formal testing in future research is warranted. Explore the mediation effects of brain states (theta activity) on 
pain intensity at weeks 0, 2, and 4. Cross-sectional analyses will examine mediation at weeks 0, 2, and 4 for 
how RHI and theta activity jointly affect pain intensity. The mediating effects model implicit in Figure 1 will be 
tested using multiple regression models. Effect sizes (Cohen’s d) will be computed for looking at the biological 
mechanism in a larger, more definitive study. Structured interviews. Transcribed interview data will be 
organized in ATLAS.ti7 (Scientific Software Development, Berlin, Germany). Content analysis10,11 will be used 
to understand the barriers and facilitators associated with undergoing qEEG measurement and perceptions on 
how the intervention works to reduce pain.  
In summary, this study is extremely important because it will provide scientific evidence on the 
efficacy of a symptom self-management intervention that cancer survivors can easily use to manage a 
distressing symptom. Furthermore, this study is innovative in that it will increase our understanding of 
how this intervention works and who will most likely experience pain reduction when using this low-
cost, accessible, and convenient intervention. 
 
 

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