Writing Interventions in Breast Cancer Patients Taking Aromatase Inhibitors

Study Overview
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Brief Summary
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Aromatase inhibitors are a powerful medication for reducing the risk of recurrence and increasing survival in postmenopausal breast cancer patients. However, these medications can lead to intolerable side effects, poor medication adherence, and increased stress levels. This project's broad objective is to assess whether an intervention can improve medication adherence and reduce physical symptoms and stress in breast cancer patients prescribed aromatase inhibitors. Participants will be randomly assigned to a values affirmation or reflective journaling condition. Interventions will be writing-based, one essay per month for six months. Physical symptoms and perceived stress will be assessed at baseline, post-intervention (one month after the intervention), and follow-up (six months from the post-intervention assessment and seven months after the end of the intervention). Furthermore, an electronic pill bottle will continuously assess daily compliance so that medication adherence rates during the intervention, post-intervention, and follow-up can be calculated.

Detailed Description
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A sample of 250 participants will be recruited and randomly assigned to either the value affirmation (N=125) or reflective journaling (N=125) condition. Participants will complete baseline measures of physical symptoms, perceived stress, and other covariates. They will also be given an electronic pill bottle that will record whether they have daily opened and closed the bottle, signifying adherence to their prescribed medication regime. This pill bottle will sync to an online dashboard. Participants in both conditions will complete a brief essay online (or via paper and pencil for those who prefer or do not have internet access) every month for six months. Value affirmation condition essays will include prompts about important, core personal values. Reflective journaling essays will have prompts that do not include any core personal value content but ask participants, in part, to write about typical daily routines. Following the conclusion of the intervention, participants will report on their levels of perceived stress and physical symptoms. Six months following the post-intervention assessment, participants will again report their perceived stress levels and physical symptoms. A sample size of 250 has been selected for feasibility and because this sample size provides at least 80% power to detect differences for all three outcomes of interest. A sub-study will be conducted on 80 of these participants who will complete their 3rd essay prompt in an fMRI scanner. In the scan session, participants will also complete a stress reactivity task. The sub-study will allow examination of the neural mechanism of value affirmation and reflective journaling to determine whether these neural mechanisms lead to enhanced medication adherence rates and reductions in stress and physical symptoms.

Official Title
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A Value Affirmation Intervention for Physical Symptoms and Medication Adherence in Breast Cancer Patients Taking Aromatase Inhibitors

Conditions
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Breast Cancer

Intervention / Treatment
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* Behavioral: Value Affirmation
* Behavioral: Reflective Journaling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Breast cancer diagnosis Prescribed an aromatase inhibitor within four weeks of enrollment or anticipates being prescribed one in the future Intention to take the prescribed aromatase inhibitor Fluency in English Own a smartphone that can support downloaded apps Exclusion Criteria for fMRI component only: Have implanted metal Have an implanted electronic medical device Have an IUD that contains metal Are currently pregnant Have a history of claustrophobia Weigh more than 300 pounds

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Value Affirmation<br>Participants in the value affirmation condition will complete six writing prompts regarding their personal values over the course of six months. For example, participants will be given a list of values and will be asked to rate them in order of importance within their own lives and write about a time when their top value was particularly important. Participants will write for about ten minutes each session. The intervention tasks will be completed on a secure, online website that each individual participant will be emailed a link to. Participants can also receive paper copies via postal mail if they prefer. | Behavioral: Value Affirmation<br>* Participants will complete writing tasks regarding their personal values.<br>|
| Active Comparator: Reflective Journaling<br>Participants in the reflective journaling condition will complete six writing prompts over the course of six months. However, the reflective journaling condition will be writing about values that are not important to them and discuss why they could be important to others. In other tasks, they will write about aspects of daily life (e.g. morning routine). Participants will write for about ten minutes each session. The intervention tasks will be completed on a secure, online website that each individual participant will be emailed a link to. Participants can also receive paper copies via postal mail if they prefer. | Behavioral: Reflective Journaling<br>* Participants will complete writing tasks regarding their least important values and discuss why they may be important to others. They will also describe aspects of daily life.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Physical Symptoms | The Breast Cancer Prevention Trial Symptom Checklist is a 43 item self-report of physical symptoms specific to breast cancer treatment. Participants rate how bothered they were by each symptom in the last 4 weeks on a five-point Likert scale ranging from 0 (Not at all) to 4 (Extremely). Item 43 is an open response question that asks participants to indicate and rate any additional symptoms they may be experiencing. Component symptom scale scores (e.g. musculoskeletal pain, cognitive problems, weight problems) will be determined by calculating the average score of the items that make up each scale. The symptom scale scores will range from 0 to 4. A total score for all the items will be calculated by adding the scores across all symptoms. Thus, the total scores will range from 0 to 172, with higher scores reflecting greater symptom severity. | Change from baseline to 1-month post-intervention and 7 months post-intervention | 
| Change in Perceived Stress | The 10-item Perceived Stress Scale is a self-reported assessment of perceptions of stress over the past month. Total scores range from 0 to 40, with higher scores indicating higher levels of perceived stress. | Change from baseline to 1-month post-intervention and 7 months post-intervention | 
| Change in Medication Adherence | Participants will receive an electronic pill bottle that syncs over the internet in real-time to indicate when a participant opens and closes the bottle. This gives a daily record of whether the participant took their medication. | Change in adherence assessed daily, throughout 1-year participation in the study | 
| Change in Self-Reported Medication Adherence | The NIH PROMIS Medication Adherence Scale (PMAS) is a 12-item scale that will be used to assess self-reported adherence behaviors and understand why a participant may be non-compliant or discontinue their medication with items that, in part, focus on one's attitude and experience with the medication of interest. Certain items are modified to reference aromatase inhibitors. | Change from baseline to 1-month post-intervention and 7 months post-intervention | 
| Health-Related Quality of Life in Breast Cancer Patients as assessed by the Functional Assessment of Cancer Therapy - Breast Cancer | The Functional Assessment of Cancer Therapy - Breast Cancer is an instrument used to assess health-related quality of life in breast cancer patients through five domains comprised of 37 items. Participants respond to each item on a five-point Likert scale. The domains include physical well-being (score ranging from 0 to 28), social/family well-being (score ranging from 0 to 28), emotional well-being (score ranging from 0 to 24), functional well-being (score ranging from 0 to 28), and the breast cancer subscale (score ranging from 0 to 40). A total score for the instrument, ranging from 0 to 148, is calculated by summing the five domain subscale scores. Higher scores are reflective of a better quality of life. | Change from baseline to 1-month post-intervention and 7 months post-intervention | 
| Neural Activity to the Affirmation Task | Participants will complete an fMRI scan while engaging with a values affirmation or a reflective journaling task. We will specifically assess neural reward response during the task assigned compared to a control comparison condition. | One session, midway through intervention | 
| Neural Activity to Stressful Task | Participants will complete an fMRI scan while engaging with a stressful and socially evaluative math task designed to give participants feedback that suggests they are not performing well compared to their peers. We will specifically assess neural threat response during this task and compare those who complete the value affirmation task before the math task to those who complete the reflective journaling task prior to the math task. | One session, midway through intervention | 
| Functional Neural Activity to Positive Stimuli | Functional neural activity to a task displaying positive vs. neutral images. Analyses will focus on a within-subject analysis for each group, as well as between-subject analyses focusing on differences in neural reward activation to positive images for self-affirmation vs. reflective journaling. ROI and connectivity analyses will focus on the reward network. Correlations with changes in included questionnaires and medication adherence will also be assessed. | One session, midway through intervention | 
| Functional Neural Activity to Negative Stimuli | Functional neural activity to a task displaying negative vs. neutral images. Analyses will focus on a within-subject analysis for each group, as well as between-subject analyses focusing on differences in neural activation to negative images for self-affirmation vs. reflective journaling. ROI and connectivity analyses will focus on the threat/salience network. Correlations with changes in included questionnaires and medication adherence will also be assessed. | One session, midway through intervention | 
| Change in Perceived Stress | The 4-item Perceived Stress Scale is a self-reported assessment of perceptions of stress over the past month. Total scores range from 0 to 16, with higher scores indicating higher levels of perceived stress. | Once a month for the 6-month duration of the intervention | 
| Change in Bodily Pain as assessed by the RAND 36-Item Health Survey 1.0 | We will utilize two questions from the RAND 36-Item Health Survey 1.0 that comprise the questionnaire's bodily pain component. The bodily pain component score is calculated by taking the average of the two pain items, which each have a range of 0 to 100. The component score also ranges from 0 to 100, where a lower score is indicative of a higher pain impact. | Change from baseline to 1-month post-intervention and 7 months post-intervention | 
| Change in Self-Reported Medication Adherence | The Basel Assessment of Adherence to Immunosuppressive Medication Scale (BAASIS) is used to assess self-reported medication adherence. Originally used to understand adherence to immunosuppressive medications, three items from the original scale will be modified to understand adherence to aromatase inhibitors in our study involving women diagnosed with breast cancer. | Once a month for the 6-month duration of the intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Recovery from Stress | The Brief Resilience Scale is a six-item instrument that will be used to assess one's ability to recover from stress. A final score for the instrument, which ranges from 1 to 5, is determined by taking the average of the six items that comprise the instrument. Scores ranging from 1 to 2.99 indicate low resilience, 3 to 4.3 signify normal resilience, and scores 4.31 to 5 reflect high resilience. | Change from baseline to 1-month post-intervention and 7 months post-intervention | 
| Change in Gratitude | The Gratitude Questionnaire-Six Item Form will be used to assess one's proneness to experience gratitude in daily life. Total scores for the instrument range from 6 to 42 where a higher score reflects a more grateful disposition. | Change from baseline to 1-month post-intervention and 7 months post-intervention | 
| Change in Well-Being as assessed by the Mental Health Continuum Short Form for Adults | The Mental Health Continuum Short Form for adults will be used as a measure of well-being. The instrument measures each facet of well-being: emotional, psychological, and social. The emotional well-being component score ranges from 0 to 15, the psychological well-being score ranges from 0 to 30, and the social well-being score ranges from 0 to 25. A total score is determined by calculating the sum of all items. The total score ranges from 0 to 70, with a higher score signifying a higher level of well-being. | Change from baseline to 1-month post-intervention and 7 months post-intervention | 
| Change in Depression Severity | The Patient Health Questionnaire is a nine-item instrument that will be utilized as a brief measure of depression severity. A total score ranges from 0 to 27 and is calculated by adding each of the nine items' scores. A higher total score signifies more severe depression levels. | Change from baseline to 1-month post-intervention and 7 months post-intervention | 
| Change in Engagement of Enjoyable Activities as assessed by the Pittsburgh Enjoyable Activities Test | The Pittsburgh Enjoyable Activities Test is a brief, ten-item measure that will be used to assess the frequency of a participant's engagement in various activities on a scale of 0 (never) to 4 (every day). A total score ranges from 0 to 40 where a higher score reflects the increased frequency of participation in enjoyable activities. | Change from baseline to 1-month post-intervention and 7 months post-intervention | 
| Change in Physical and Mental Fatigue | The Pittsburgh Fatigability Scale is a self-report questionnaire that assesses one's physical and mental fatigue in relation to activities with specific intensities and durations. Mental and physical fatigue component scores range from 0 to 50 and are determined by adding the scores of the items within the components. A higher score reflects a greater perceived physical/mental fatigability. | Change from baseline to 1-month post-intervention and 7 months post-intervention | 
| Change in Sleep Measures | The Pittsburgh Sleep Quality Index will be used to obtain self-reported ratings of sleep. The instrument contains numerous sleep-related components, all with score ranges from 0 to 3. A higher subjective sleep quality component score signifies poor sleep quality. A higher sleep latency component score signifies increased sleep latency. An increased sleep duration component score signifies decreased sleep duration. A greater sleep efficiency component score reflects decreased efficiency. A higher sleep disturbance component score represents higher levels of sleep disturbance. A greater use of sleep medication component score signifies increased sleep medication use. A higher daytime dysfunction component score reflects increased daytime dysfunction. Finally, a global score is determined by calculating the sum of the seven component scores. The global score ranges from 0 to 21, where a higher score signifies decreased sleep quality. | Change from baseline to 1-month post-intervention and 7 months post-intervention | 
| Change in Positive and Negative Emotional Style | The Positive and Negative Emotional Style instrument is a twelve-item measure of emotional style which asks participants how accurately six positive and six negative adjectives describe how they felt during the past day. Positive and negative emotional style component scores are determined by calculating the sum of the adjective ratings within each component. Component scores range from 0 to 24, with a high score signifying increased positive and negative mood on the respective scales. | Change from baseline to 1-month post-intervention and 7 months post-intervention | 
| Change in Self-Esteem | The Rosenberg Self Esteem Scale is a ten-item instrument that assesses global self-esteem. A total score is determined by calculating the sum of the item scores. The range of total scores is 10 to 40. Higher total scores reflect higher self-esteem. | Change from baseline to 1-month post-intervention and 7 months post-intervention | 
| Changes in Perceived Social Support | The Social Provisions Scale is a twenty-four-item measure of perceived social support that asks participants to think about the support they receive in current relationships. The six-component scores (attachment, social integration, reassurance of worth, reliable alliance, guidance, opportunity for nurturance) are determined by adding the scores of the items that comprise each component's scale. Component scores range from 4 to 16. A total score can be calculated by summing all of the items in the scale. The total scale score ranges from 4 to 96, with higher scores indicating increased levels of perceived support. | Change from baseline to 1-month post-intervention and 7 months post-intervention | 
| Change in Spontaneous Self-Affirmation | The Spontaneous Self-Affirmation Measure is an instrument that asks participants how they think about themselves when they feel threatened or anxious to assess the tendency to utilize self-affirming cognitions. Component scores are used to determine if participants focus on personal strengths and attributes, values and principles, or important social relationships. A total score, ranging from 1 to 7, is calculated by taking the average of the three component scores. A higher total score reflects an increased tendency to utilize self-affirming cognitions when one feels threatened or anxious. | Change from baseline to 1-month post-intervention and 7 months post-intervention | 
| Change in Loneliness | The UCLA Loneliness scale will be used to measure subjective feelings of loneliness and social isolation. A total score that ranges from 20 to 80 is calculated by summing the score of each item. A higher total score signifies increased feelings of loneliness. | Change from baseline to 1-month post-intervention and 7 months post-intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer, Aromatase Inhibitors, Value Affirmation