The Effect of Pain Neuroscience Education and Behavioural Graded Activity on Chronic Pain in Breast Cancer Survivors

Study Overview
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Brief Summary
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Chronic pain in breast cancer survivors (BCS) is of considerable concern as it impacts the health-related quality of life (HRQoL) and activities of daily living negatively. Over the past decades, awareness has raised the value of pain neuroscience education (PNE) in chronic pain. However, pain education remains underused in oncology and is often restricted to a biomedical management, which falls short in explaining persistent pain following cancer. Since PNE alone has rather small effect sizes, it should ideally be combined with a physical part, 'behavioural graded activity' (BGA). Therefore, the purpose of this study is to investigate the effectiveness of PNE with BGA compared to usual care on chronic pain in BCS. A multi-centre, parallel, two-arm, double-blinded superiority with a three months intervention and two years follow-up will be conducted in 200 BCS with chronic pain. These will be randomly assigned to the intervention or usual care group. The intervention group will receive 6 sessions, in which PNE and BGA will be integrated. Whereas, the usual care group will receive an information leaflet regarding Pain in and after cancer. The primary objective of the present study is to examine whether the combination of PNE and BGA has an added value in decreasing the pain intensity compared to the usual care in BCS with chronic pain. The secondary objectives are to investigate whether the combination of PNE and BGA has the ability to reduce endogenous hyperalgesia and improve HRQoL compared to the usual care in BCS with chronic pain.

Official Title
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The Effect of Pain Neuroscience Education and Behavioural Graded Activity Compared to Usual Care on Chronic Pain in Breast Cancer Survivors: a Randomised Controlled Trial

Conditions
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Breast Neoplasms, Survivors, Chronic Pain

Intervention / Treatment
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* Other: Pain Neuroscience Education
* Other: Behavioural Graded Activity
* Other: Usual care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: To meet the definition introduced by the National Cancer Institute's Office of Cancer Survivorship, in which a cancer survivor is a patient with a history of cancer that is beyond the acute diagnosis and treatment phase. Patients need to be cancer-free and should have finished their primary treatment with a curative intent for at least 3 months prior to study participation. Adjuvant hormonal therapy and immunotherapy form the exception to the rule and are tolerated. To report a pain severity of at least 3 out of 10 on pain visual analogue scale. To be able to speak and read in Dutch in order to give informed consent and to complete the assessment tools. Written and signed consent will be obtained from all participants. Exclusion Criteria: Suffering from dementia or cognitive impairment (unable to understand the test instructions and/or Mini Mental State Examination score <23/30). Suffering from severe psychological or psychiatric diseases. Diagnosis of new neoplasms or metastases.

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pain Neuroscience Education + Behavioural Graded Activity<br>Patients allocated to the intervention group will receive a 12-week treatment program that consists of 6 sessions, in which 'Pain Neuroscience Education' and 'Behavioural Graded Activity' will be integrated. | Other: Pain Neuroscience Education<br>* Pain Neuroscience Education (PNE) teaches patients about complex pain mechanisms known to be of importance in pain following breast cancer such as malfunctioning of the endogenous analgesic system and pain memories.<br>Other: Behavioural Graded Activity<br>* Patients in the experimental group will receive a behavioural treatment integrated within the concepts of operant conditioning. The purpose of Behavioural Graded Activity (BGA) is to increase the level of physical activity in the patient's daily lives in a time-contingent manner. On top of that, a healthy behaviour will be positively reinforced to consequently create a withdrawal of the attention towards pain behaviour, which is seen as an unreliable alarm sign in chronic pain patients. The implementation of BGA after PNE is described in the guideline reported by the International Association for the Study of Pain.<br>|
| Active Comparator: Usual care<br>Patients allocated to the control group will receive an information leaflet from Kom op tegen kanker regarding Pain in and after cancer. | Other: Usual care<br>* The content of the leaflet has a biomedical approach in explaining pain and providing information on the different pain medication classes. This leaflet is mostly available in waiting rooms of oncology centres and units of the Flemish part of Belgium.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in pain intensity and pain interference | Change between baseline (T1) and 3 months post-intervention (T3) Measured with the 'Brief Pain Inventory' The minimum and maximum values: 0, 10 Higher score means a worse outcome | T1: baseline (within one week before randomisation) and T3: 3 months after intervention (w 26) | 
| Self-reported pain intensity and pain interference | Measured with the 'Brief Pain Inventory' The minimum and maximum values: 0, 10 Higher score means a worse outcome | T1: baseline (within one week before randomisation) | 
| Self-reported pain intensity and pain interference | Measured with the 'Brief Pain Inventory' The minimum and maximum values: 0, 10 Higher score means a worse outcome | T2: after finishing intervention (week 13) | 
| Self-reported pain intensity and pain interference | Measured with the 'Brief Pain Inventory' The minimum and maximum values: 0, 10 Higher score means a worse outcome | T3: 3 months after intervention (week 26) | 
| Self-reported pain intensity and pain interference | Measured with the 'Brief Pain Inventory' The minimum and maximum values: 0, 10 Higher score means a worse outcome | T4: 1 year after intervention (week 64) | 
| Self-reported pain intensity and pain interference | Measured with the 'Brief Pain Inventory' The minimum and maximum values: 0, 10 Higher score means a worse outcome | T5: 2 years after intervention (week 116) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Self-reported health-related quality of life | Measured with the 'European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC-QLQ-C30)' The minimum and maximum values: 0, 100 Higher score means a better outcome | T1: baseline (within one week before randomisation), T2: after finishing intervention (w 13), T3: 3 months after intervention (w 26), T4: 1 year after intervention (w 64) and T5: 2 years after intervention (w 116) | 
| Temperature detection threshold | Assessed by the Medoc TSA-II Neurosensory Analyzer. | T1: baseline (within one week before randomisation), T2: after finishing intervention (w 13) and T3: 3 months after intervention (w 26) | 
| Pain detection threshold | Assessed by the digital algometer, the Medoc TSA-II Neurosensory Analyzer and a manual blood pressure cuff. | T1: baseline (within one week before randomisation), T2: after finishing intervention (w 13) and T3: 3 months after intervention (w 26) | 
| Pain tolerance threshold | Assessed by a manual blood pressure cuff. | T1: baseline (within one week before randomisation), T2: after finishing intervention (w 13) and T3: 3 months after intervention (w 26) | 
| Endogenous pain inhibition | Assessed objectively by conditioned pain modulation paradigm. A manual blood pressure is the conditioned stimulus, and the digital algometer and the Medoc TSA-II Neurosensory Analyzer are testing stimuli. | T1: baseline (within one week before randomisation), T2: after finishing intervention (w 13) and T3: 3 months after intervention (w 26) | 
| Endogenous pain facilitation | Assessed objectively by temporal summation paradigm. Ten testing stimuli will be applied, and subjects will be asked to rate their pain intensity on the first, fifth and tenth stimulus by using the Visual Analogue Scale. | T1: baseline (within one week before randomisation), T2: after finishing intervention (w 13) and T3: 3 months after intervention (w 26) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Behavioural Graded Activity, Pain Neuroscience Education