Optimizing Psychological Treatment for Pain After Breast Cancer

Optimizing Psychological Treatment for Pain After Breast Cancer: A Factorial Design Study

The present study aims to optimize psychological treatment for pain after breast cancer by identifying active treatment components. Specifically, a factorial design will be used to evaluate the efficacy and change processes of three psychological treatment components, which have been shown to be efficacious in the treatment of pain after breast cancer.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Pain, Chronic
• Intervention / Treatment: Behavioral: Mindful attention; Behavioral: Decentering; Behavioral: Values and committed action

Detailed Description

There is a need for optimization of psychological treatment of pain after breast cancer. Optimization relies on knowledge about the active components of existing treatments. Guided by the Multiphase Optimization Strategy (MOST), the present study aims to address this challenge by identifying active contemporary cognitive behavioral therapy components for breast cancer-related pain. Consistent with the Optimization phase of the MOST framework, a full factorial design will be used to evaluate the efficacy and change processes of three selected treatment components.The overall hypothesis is that the three components will target key maintaining psychological factors in pain, thus leading to reductions in the primary outcomes of pain intensity and -interference. The treatment components and their hypothesized mechanisms of action are as follows:

1. Mindful attention practices will increase attentional control (i.e., the ability to intentionally focus and intentionally shift one's attention), thereby reducing pain hypervigilance, leading to reductions in pain intensity and -interference.
2. Decentering practices will reduce fusion with thoughts (i.e., getting caught up in one's thoughts, feelings and inner experiences), thereby reducing pain catastrophizing, leading to reductions in pain intensity and -interference.
3. Values and committed action (i.e., behavior congruent with one's values) will increase acceptance of discomfort and reduce avoidant behavior, leading to reductions in pain intensity and -interference.

• Study Type: Interventional
• Enrollment (Anticipated): 185
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Robert Zachariae, DMSc; Phone Number: +4587165878; Email: bzach@rm.dk

Study Locations

• Denmark
  • Central Denmark Region
    • Aarhus, Central Denmark Region, Denmark, 8000
      • Recruiting
      • Aarhus University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Diagnosis of primary breast cancer stage I-III
• Min. 6 months post primary treatment (i.e., surgery, chemotherapy, and/or radiotherapy). Endocrine treatment, e.g., Letrozol or Tamoxifen, and/or Zoledronic acid and/or Herceptin treatment is allowed during study participation
• Pain corresponding to a pain score of >= 3 on pain intensity and/or pain interference measured by 11-point Numeric Rating Scales (NRSs)
• Sufficient ability to communicate in Danish
• Sufficient ability to participate in an online-delivered intervention

Exclusion Criteria:

• Non-curable breast cancer (stage IV)
• Breast cancer recurrence
• Bilateral breast cancer
• Other current cancer disease
• Other primary pain condition (e.g., fibromyalgia)
• Current severe psychiatric disorder (e.g., psychosis) hindering study participation
• Insufficient ability to communicate in Danish
• Insufficient ability to participate in an online-delivered intervention

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Waitlist control; Participants randomized to condition 1 are not offered any treatment components immediately upon enrollment, but will be offered a treatment component of own choice at the end of the study. Total number of sessions: 2 (2 contact hours) following study completion.
Experimental: Mindful attention; Participants randomized to condition 2 will receive the Mindful attention treatment component. Total number of sessions: 2 (2 contact hours).	Behavioral: Mindful attention; The Mindful attention treatment component consists of a breathing exercise and is operationalized as two sessions (1 hour each) delivered over two weeks, i.e., one session per week, with homework between sessions. Sessions will be delivered online.
Experimental: Decentering; Participants randomized to condition 3 will receive the Decentering treatment component. Total number of sessions: 2 (2 contact hours).	Behavioral: Decentering; The Decentering treatment component consists of a guided imagery exercise and is operationalized as two sessions (1 hour each) delivered over two weeks, i.e., one session per week, with homework between sessions. Sessions will be delivered online.
Experimental: Values and committed action; Participants randomized to condition 4 will receive the Values and committed action treatment component. Total number of sessions: 2 (2 contact hours).	Behavioral: Values and committed action; The Values and committed action treatment component consists of identification of personal values and committed action, and is operationalized as two sessions (1 hour each) delivered over two weeks, i.e., one session per week, with homework between sessions. Sessions will be delivered online.
Experimental: Mindful attention + Decentering; Participants randomized to condition 5 will receive the Mindful attention treatment component and the Decentering treatment component in different orders. Total number of sessions: 4 (4 contact hours).	Behavioral: Mindful attention; The Mindful attention treatment component consists of a breathing exercise and is operationalized as two sessions (1 hour each) delivered over two weeks, i.e., one session per week, with homework between sessions. Sessions will be delivered online.; Behavioral: Decentering; The Decentering treatment component consists of a guided imagery exercise and is operationalized as two sessions (1 hour each) delivered over two weeks, i.e., one session per week, with homework between sessions. Sessions will be delivered online.
Experimental: Mindful attention + Values and committed action; Participants randomized to condition 6 will receive the Mindful attention treatment component and the Values and committed action treatment component in different orders. Total number of sessions: 4 (4 contact hours).	Behavioral: Mindful attention; The Mindful attention treatment component consists of a breathing exercise and is operationalized as two sessions (1 hour each) delivered over two weeks, i.e., one session per week, with homework between sessions. Sessions will be delivered online.; Behavioral: Values and committed action; The Values and committed action treatment component consists of identification of personal values and committed action, and is operationalized as two sessions (1 hour each) delivered over two weeks, i.e., one session per week, with homework between sessions. Sessions will be delivered online.
Experimental: Decentering + Values and committed action; Participants randomized to condition 7 will receive the Decentering treatment component and the Values and committed action treatment component in different orders. Total number of sessions: 4 (4 contact hours).	Behavioral: Decentering; The Decentering treatment component consists of a guided imagery exercise and is operationalized as two sessions (1 hour each) delivered over two weeks, i.e., one session per week, with homework between sessions. Sessions will be delivered online.; Behavioral: Values and committed action; The Values and committed action treatment component consists of identification of personal values and committed action, and is operationalized as two sessions (1 hour each) delivered over two weeks, i.e., one session per week, with homework between sessions. Sessions will be delivered online.
Experimental: Mindful attention + Decentering + Values and committed action; Participants randomized to condition 8 will receive the Mindful attention treatment component, the Decentering treatment component, and the Values and committed action treatment component in different orders. Total number of sessions: 6 (6 contact hours).	Behavioral: Mindful attention; The Mindful attention treatment component consists of a breathing exercise and is operationalized as two sessions (1 hour each) delivered over two weeks, i.e., one session per week, with homework between sessions. Sessions will be delivered online.; Behavioral: Decentering; The Decentering treatment component consists of a guided imagery exercise and is operationalized as two sessions (1 hour each) delivered over two weeks, i.e., one session per week, with homework between sessions. Sessions will be delivered online.; Behavioral: Values and committed action; The Values and committed action treatment component consists of identification of personal values and committed action, and is operationalized as two sessions (1 hour each) delivered over two weeks, i.e., one session per week, with homework between sessions. Sessions will be delivered online.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain intensity (11-point Numeric Rating Scale, NRS)	The NRS is a validated, self-report instrument assessing pain intensity during the last week. Answer format range: 0 (no pain) to 10 (worst possible pain); total score range: 0-10. A higher score yields more pain.	Baseline (T1) to 1 week after last session (Post-intervention, T2)
Pain interference (the 7-item subscale of the Brief Pain Inventory, BPI)	The BPI is a validated, self-report instrument assessing clinical pain. The BPI pain interference subscale assesses pain interference during the last week across 7 domains, i.e., general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Answer format range: 0 (no interference) to 10 (maximal interference); total score range: 0-10. A higher score yields more pain.	Baseline (T1) to 1 week after last session (Post-intervention, T2)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain intensity (11-point Numeric Rating Scale, NRS)	The NRS is a validated, self-report instrument assessing pain intensity during the last week. Answer format range: 0 (no pain) to 10 (worst possible pain); total score range: 0-10. A higher score yields more pain.	Baseline (T1) to 12 weeks after post-intervention (T2) (Follow-up, T3)
Pain intensity (11-point Numeric Rating Scale, NRS)	Pain intensity during the last 24 hours will be assessed every day for 6 days following the first session (Td) for each treatment component using the NRS. Answer format range: 0 (no pain) to 10 (worst possible pain); total score range: 0-10. A higher score yields more pain.	Every day for 6 days following the first session (Td) for each treatment component
Pain interference (the 7-item subscale of the Brief Pain Inventory, BPI)	The BPI is a validated, self-report instrument assessing clinical pain. The BPI pain interference subscale assesses pain interference during the last week across 7 domains, i.e., general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Answer format range: 0 (no interference) to 10 (maximal interference); total score range: 0-10. A higher score yields more pain.	Baseline (T1) to 12 weeks after post-intervention (T2) (Follow-up, T3)
Pain interference (1 aggregated item assessing pain interference during the last 24 hours within the 7 domains measured with the Brief Pain Inventory, BPI, interference subscale)	Pain interference during the last 24 hours will be assessed every day for 6 days following the first session (Td) for each treatment component using 1 aggregated item assessing pain interference across the 7 domains measured with the BPI interference subscale, i.e., general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Answer format range: 0 (no interference) to 10 (maximal interference); total score range: 0-10. A higher score yields more pain..	Every day for 6 days following the first session (Td) for each treatment component
Pain burden (11-point Numeric Rating Scale, NRS)	The NRS is a validated, self-report instrument assessing pain burden during the last week. Answer format range: 0 (no burden) to 10 (maximal burden); total score range: 0-10. A higher score yields more pain burden.	Baseline (T1) to 1 week after last session (Post-intervention, T2)
Pain burden (11-point Numeric Rating Scale, NRS)	The NRS is a validated, self-report instrument assessing pain burden during the last week. Answer format range: 0 (no burden) to 10 (maximal burden); total score range: 0-10. A higher score yields more pain burden.	Baseline (T1) to 12 weeks after post-intervention (T2) (Follow-up, T3)
Pain quality (the 22-item pain descriptors from the McGill Pain Questionnaire, MPQ)	The pain descriptors from the MPQ constitutes a validated, self-report instrument assessing pain quality (i.e., pain type, namely continuous pain, intermittent pain, neuropathic pain, affective pain) during the last week. Answer format range: 0 (no pain) to 10 (worst possible pain); total score range: 0-60 (continuous, neuropathic and intermittent pain), 0-40 (affective pain). Higher scores yield more pain.	Baseline (T1) to 1 week after last session (Post-intervention, T2)
Pain quality (the 22-item pain descriptors from the McGill Pain Questionnaire, MPQ)	The pain descriptors from the MPQ constitutes a validated, self-report instrument assessing pain quality (i.e., pain type, namely continuous pain, intermittent pain, neuropathic pain, affective pain) during the last week. Answer format range: 0 (no pain) to 10 (worst possible pain); total score range: 0-60 (continuous, neuropathic and intermittent pain), 0-40 (affective pain). Higher scores yield more pain.	Baseline (T1) to 12 weeks after post-intervention (T2) (Follow-up, T3)
Pain frequency (1 item)	Pain frequency will be assessed using a single question. Answer format range: 1 (never) to 5 (all the time); total score range: 1-5. Higher scores yield higher pain frequency.	Baseline (T1) to 1 week after last session (Post-intervention, T2)
Pain frequency (1 item)	Pain frequency will be assessed using a single question. Answer format range: 1 (never) to 5 (all the time); total score range: 1-5. Higher scores yield higher pain frequency.	Baseline (T1) to 12 weeks after post-intervention (T2) (Follow-up, T3)
Pain catastrophizing (the 13-item Pain Catastrophizing Scale, PCS)	The PCS is a validated, self-report instrument assessing pain catastrophizing. Answer format range: 0 (not at all) to 4 (all the time); total score range: 0-52. Higher scores yield more pain catastrophizing.	Baseline (T1) to 1 week after last session (Post-intervention, T2)
Pain catastrophizing (the 13-item Pain Catastrophizing Scale, PCS)	The PCS is a validated, self-report instrument assessing pain catastrophizing. Answer format range: 0 (not at all) to 4 (all the time); total score range: 0-52. Higher scores yield more pain catastrophizing.	Baseline (T1) to 12 weeks after post-intervention (T2) (Follow-up, T3)
Psychological distress (the 14-item Hospital Anxiety and Depression Scale, HADS)	The HADS is a validated, self-report instrument assessing psychological distress during the last week. Answer format range: 0 (not at all or never) to 3 (most or all of the time); total score range 0-42. Higher scores yield more psychological distress.	Baseline (T1) to 1 week after last session (Post-intervention, T2)
Psychological distress (the 14-item Hospital Anxiety and Depression Scale, HADS)	The HADS is a validated, self-report instrument assessing psychological distress during the last week. Answer format range: 0 (not at all or never) to 3 (most or all of the time); total score range 0-42. Higher scores yield more psychological distress.	Baseline (T1) to 12 weeks after post-intervention (T2) (Follow-up, T3)
Fear of cancer recurrence (the 9-item Fear of Cancer Recurrence Inventory, FCRI)	The FCRI is a validated, self-report instrument assessing fear of cancer recurrence during the last month. Answer format range: 0 (not at all) to 4 (a great deal); total score range 0-36. Higher scores yield more fear of cancer recurrence.	Baseline (T1) to 1 week after last session (Post-intervention, T2)
Fear of cancer recurrence (the 9-item Fear of Cancer Recurrence Inventory, FCRI)	The FCRI is a validated, self-report instrument assessing fear of cancer recurrence during the last month. Answer format range: 0 (not at all) to 4 (a great deal); total score range 0-36. Higher scores yield more fear of cancer recurrence.	Baseline (T1) to 12 weeks after post-intervention (T2) (Follow-up, T3)
Well-being (the 5-item WHO-5 Well-Being Index, WHO-5)	The WHO-5 is a validated, self-report instrument assessing current well-being. Answer format range: 0 (at no time) to 5 (all the time); total score range: 0-100. Higher scores yield more well-being.	Baseline (T1) to 1 week after last session (Post-intervention, T2)
Well-being (the 5-item WHO-5 Well-Being Index, WHO-5)	The WHO-5 is a validated, self-report instrument assessing current well-being. Answer format range: 0 (at no time) to 5 (all the time); total score range: 0-100. Higher scores yield more well-being.	Baseline (T1) to 12 weeks after post-intervention (T2) (Follow-up, T3)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Moderator: Socio-demographic characteristics	Socio-demographic characteristics will be assessed using single questions (e.g., marital status, income, work status).	Baseline (T1)
Moderator: Clinical characteristics	Clinical data will be obtained from the register of the national Danish Breast Cancer Group (DCBG), including disease characteristics (e.g., date of diagnosis; endocrine receptor status; menopausal status) and allocated treatment protocol (e.g., type of primary surgery; radiotherapy (yes/no); endocrine therapy (yes/no); Herceptin treatment (yes/no); Zoledronic acid (yes/no)).	Baseline (T1)
Moderator: Treatment expectancy	Treatment expectancy will be assessed using a single question regarding the extent to which the participant expects that the intervention to reduce pain and increase overall well-being. Answer format range: 1 (not at all) to 5 (a great deal); total score range: 1-5. Higher scores indicate stronger expectations that the intervention will lead to a positive outcome.	Baseline (T1)
Moderator: Therapeutic alliance (the 12-item Working Alliance Inventory, WAI) Revised Short Form	The WAI is a validated, self-report instrument assessing therapeutic alliance. Answer format range: 1 (never) to 7 (all the time); total score range: 12-84. Higher scores yield a stronger therapeutic alliance.	1 week after last session (Post-intervention, T2)
Moderator: Homework	Homework will be assessed with 4 single items related to i) whether homework has been conducted (yes/no), and the ii) type, iii) frequency (number of days per week), and iv) duration of completed homework (average number of minutes per day).	Before each session (Ts), 1 week after last session (Post-intervention, T2), and 12 weeks after post-intervention (T2) (follow-up, T3)
Mediator: Mindful attention (the 15-item Mindful Attention Awareness Scale, MAAS)	The MAAS is a validated, self-report instrument assessing individual differences in the frequency of mindful states over time. Answer format range: 1 (almost always) to 6 (almost never); total score range: 1-6. Higher scores yield higher levels of mindful attention.	Baseline (T1) to 1 week after last session (Post-intervention, T2)
Mediator: Mindful attention (the 15-item Mindful Attention Awareness Scale, MAAS)	The MAAS is a validated, self-report instrument assessing individual differences in the frequency of mindful states over time. Answer format range: 1 (almost always) to 6 (almost never); total score range: 1-6. Higher scores yield higher levels of mindful attention.	Baseline (T1) to 12 weeks after post-intervention (T2) (Follow-up, T3)
Mediator: Mindful attention (2 items from the 15-item Mindful Attention Awareness Scale, MAAS)	MAAS items 13 and 7 will be assessed before each session (Ts). Answer format range: 1 (almost always) to 6 (almost never). Higher scores yield higher levels of mindful attention.	Before each session (Ts)
Mediator: Mindful attention (1 item from the 15-item Mindful Attention Awareness Scale, MAAS)	MAAS item 7 will be assessed every day for 6 days following the first session (Td) for each treatment component. Answer format range: 1 (almost always) to 6 (almost never). Higher scores yield higher levels of mindful attention.	Every day for 6 days following the first session for each treatment component (Td)
Mediator: Decentering (the 11-item Experiences Questionnaire, EQ)	The EQ is a validated, self-report instrument assessing decentering. Answer format range: 1 (do not agree at all) to 5 (agree completely); total score range: 11-55. Higher scores yield higher levels of decentering.	Baseline (T1) to 1 week after last session (Post-intervention, T2)
Mediator: Decentering (the 11-item Experiences Questionnaire, EQ)	The EQ is a validated, self-report instrument assessing decentering. Answer format range: 1 (do not agree at all) to 5 (agree completely); total score range: 11-55. Higher scores yield higher levels of decentering.	Baseline (T1) to 12 weeks after post-intervention (T2) (Follow-up, T3)
Mediator: Decentering (2 items from the 11-item Experiences Questionnaire, EQ)	EQ items 5 and 7 will be assessed before each session (Ts). Answer format range: 1 (do not agree at all) to 5 (agree completely). Higher scores yield higher levels of decentering.	Before each session (Ts)
Mediator: Decentering (1 item from the 11-item Experiences Questionnaire, EQ)	EQ item 5 will be assessed every day for 6 days following the first session (Td) for each treatment component. Answer format range: 1 (do not agree at all) to 5 (agree completely). Higher scores yield higher levels of decentering.	Every day for 6 days following the first session for each treatment component (Td)
Mediator: Pain acceptance and activity engagement (the 20-item Chronic Pain Acceptance Scale, CPAS)	The CPAS is a validated, self-report instrument assessing pain acceptance and activity engagement. Answer format range: 0 (never true) to 6 (always true); subscale score range: 0-54 (pain acceptance subscale), 0-66 (activity engagement subscale). Higher scores yield more acceptance and activity engagement.	Baseline (T1) to 1 week after last session (Post-intervention, T2)
Mediator: Pain acceptance and activity engagement (the 20-item Chronic Pain Acceptance Scale, CPAS)	The CPAS is a validated, self-report instrument assessing pain acceptance and activity engagement. Answer format range: 0 (never true) to 6 (always true); subscale score range: 0-54 (pain acceptance subscale), 0-66 (activity engagement subscale). Higher scores yield more acceptance and activity engagement.	Baseline (T1) to 12 weeks after post-intervention (T2) (Follow-up, T3)
Mediator: Activity engagement (2 items from the 20-item Chronic Pain Acceptance Scale, CPAS)	CPAS items 1 and 12 will be assessed before each session (Ts). Answer format range: 0 (never true) to 6 (always true). Higher scores yield more activity engagement.	Before each session (Ts)
Mediator: Activity engagement (1 item from the 20-item Chronic Pain Acceptance Scale, CPAS)	CPAS item 1 will be assessed every day for 6 days following the first session (Td) for each treatment component. Answer format range: 0 (never true) to 6 (always true). Higher scores yield more activity engagement	Every day for 6 days following the first session for each treatment component (Td)

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Danish Council for Independent Research
• Investigators: Principal Investigator: Robert Zachariae, DMSc, University of Aarhus

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2022
• Primary Completion (Anticipated): October 1, 2023
• Study Completion (Anticipated): October 1, 2024

Study Registration Dates

• First Submitted: June 27, 2022
• First Submitted That Met QC Criteria: June 30, 2022
• First Posted (Actual): July 5, 2022

Study Record Updates

• Last Update Posted (Actual): November 2, 2022
• Last Update Submitted That Met QC Criteria: November 1, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Breast Cancer; Pain; Contemporary cognitive behavioral therapy; Mindful attention; Decentering; Values and committed action; The Multiphase Optimization Strategy (MOST); Psychological pain treatment; Treatment mediators
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Pain; Neurologic Manifestations; Breast Diseases; Breast Neoplasms; Chronic Pain; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine
• Other Study ID Numbers: MOST Pain

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: All data underlying publication will be shared in accordance with current data sharing regulations at host institutions.
• IPD Sharing Time Frame: 6 months after publication
• IPD Sharing Access Criteria: Researchers aiming to publish IPD meta-analyses
• IPD Sharing Supporting Information Type: Study Protocol

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No