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

Chronic Pain Clinical Trial

— BCS-PAIN  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04531917
• Other study ID #: 11B1920N_BCS-PAIN
• Status: Active, not recruiting
• Phase: N/A
• Start date: October 12, 2020
• Est. completion date: April 2024

Study information

• Verified date: November 2022
• Source: Universitair Ziekenhuis Brussel
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 122
• Est. completion date: April 2024
• Est. primary completion date: April 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Neoplasms
• Chronic Pain
• Mastodynia
• Survivors

Intervention

Other:
• Pain Neuroscience Education
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.
• Behavioural Graded Activity
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.
• Usual care
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.

Locations

Country	Name	City	State
Belgium	Vrije Universiteit Brussel (VUB)	Jette	Brussel

Sponsors (3)

Lead Sponsor	Collaborator
Universitair Ziekenhuis Brussel	Fund for Scientific Research, Flanders, Belgium, Vrije Universiteit Brussel

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Self-reported pain	Measured with the 'Visual Analogue Scale'; The minimum and maximum values: 0mm, 100mm; Higher score means a worse 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)
Other	Self-reported neuropathic pain	Measured with the 'Douleur Neuropatique 4'; The minimum and maximum values: 0, 10; Higher score means a worse outcome; A score of 4 or higher indicates neuropathic pain	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)
Other	Self-reported central sensitization	Measured with the 'Central Sensitization Index'; The minimum and maximum values: 0, 100; Higher score means a worse outcome; A score of 40 or higher indicates the presence of central sensitization	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)
Other	Self-reported physical activity level	Measured with the 'International Physical Activity Questionnaire short form'; Total physical activity in MET-min/week and time spent sitting	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)
Other	Self-reported physical activity level	Measured with the 'logbook'; Subjects enrolled in the intervention arm will have to fill in the logbook on daily basis.	During the intervention and T2: after finishing intervention (w 13)
Other	Self-reported sleep quality	Measured with the 'Pittsburgh Sleep Quality Index'; The minimum and maximum values: 0, 21; Higher score means a worse outcome; A scores above 5 indicates poor global sleep quality	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)
Other	Self-reported insomnia severity	Measured with the 'Insomnia Severity Index'; The minimum and maximum values: 0, 28; Higher score means a worse outcome; A scores of 8 or higher indicates insomnia	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)
Other	Self-reported fatigue	Measured with the 'Fatigue Severity Scale'; The minimum and maximum values: 9, 63; Higher score means a worse 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)
Other	Self-reported pain cognitions (pain catastrophizing)	Measured with the 'Pain Catastrophizing Scale'; The minimum and maximum values: 0, 52; Higher score means a worse outcome; A scores of 30 or higher indicates pain catastrophizing thoughts	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)
Other	Self-reported pain cognitions (perceived injustice)	Measured with the 'Injustice Experience Questionnaire'; The minimum and maximum values: 0, 48; Higher score means a worse 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)
Other	Self-reported pain cognitions (illness perception)	Measured with the 'the Brief Illness Perception Questionnaire'; The minimum and maximum values: 0, 10; Higher score means a worse 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)
Other	Self-reported pain cognitions (pain vigilance and awareness)	Measured with the 'Pain Vigilance and Awareness questionnaire'; The minimum and maximum values: 0, 90; Higher score means a worse 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)
Other	Self-reported depression	Measured with the 'Depression, Anxiety, Stress Scale'; The minimum and maximum values: 0, 21; Higher score means a worse 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)
Other	Self-reported anxiety	Measured with the 'Depression, Anxiety, Stress Scale'; The minimum and maximum values: 0, 21; Higher score means a worse 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)
Other	Self-reported stress	Measured with the 'Depression, Anxiety, Stress Scale'; The minimum and maximum values: 0, 21; Higher score means a worse 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)
Other	Treatment adherence	Patient adherence for the treatment sessions will be calculated as the ratio of the number of treatment sessions that were actually carried out versus the number of prescribed sessions.	During the intervention and T2: after finishing intervention (w 13)
Other	Treatment compliance	Compliance will be calculated as the ratio of the total training duration (recorded in the logbooks) versus the prescribed total training duration, multiplied by 100.	During the intervention and T2: after finishing intervention (w 13)
Other	The presence of axillary web syndrome	The diagnosis of Axillary Web Syndrome (AWS) will be made clinically.; Scored on 5-point Likert scale (totally disagree, disagree, don't disagree/agree, agree, totally agree); The presence of rope-like cords in the axilla to the wrist is assessed by inspection and/or palpation.	T1: baseline (within one week before randomisation)
Other	The presence of lymphedema	Lymphedema will be clinically diagnosed: The Stemmer sign is positive if the assessor is unable to pinch (between his/her thumb and index finger) the dorsal skin of proximal phalanx (second or third finger). A positive test confirms the presence of primary and secondary lymphedema of the arm(s).; Single circumference measurement will only be performed if unilateral lymphedema is suspected. The arm circumference will be measured by a nylon tape measure with an accuracy of 1mm. The tape measure will be placed around the arm without tightening the tape at 30cm above the styloid process. Lymphedema is present if there is at least a difference of 10% between both arms.	T1: baseline (within one week before randomisation)
Other	The presence of arthralgia	To assess arthralgia the assessor will ask the patient two questions: "Do you experience symmetrical pain in the left and right shoulders, elbows, wrists, fingers, hips, knees, ankles and/or toes?" and "Do you experience morning stiffness? And if so, for how many minutes?"	T1: baseline (within one week before randomisation)
Other	Detection of inflammation or adhesion of the scar tissue	The scar tissue will be clinically scored. First, the assessor will inspect the affected (and painful) region for possible skin damage and will be looking for: wound disruption, hematoma (bruising), abscess (cavity filled with pus) and seroma (cavity filled with transparent liquid). Second, the he will inspect the presence of a possible inflammation process of the scar tissue and will be looking for signs such as: warmth, redness, etc. Third, he will assess the mobility of the scar. During this manual test, will be assessed whether the scar is moving relative to the underlying layers, which will be scored on a 5-point Likert scale with response possibilities: (totally disagree, disagree, don't disagree/agree, agree, totally agree).	T1: baseline (within one week before randomisation)
Other	Self-reported health care cost	Measured with the 'Medical Consumption Questionnaire'; 38 questions to quantify the direct medical costs of a patients' total medical consumption, encompassing additional diagnostics, consultations, surgery including stay in hospitals, physiotherapy, medication and aids prescribed by the general practitioner as well as medication and aids purchased by the patients themselves.	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)
Other	Self-reported work absenteeism and productivity loss at work	Measured with the 'Productivity Cost Questionnaire'; 20 questions to quantify the indirect costs outside health care but related to the disease (e.g. the costs due to absence of work and possible decreased productivity losses of paid and unpaid work).	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)
Other	Self-reported overall health status	Measured with the 'EuroQol 5D instrument (EQ-5D-5L)'; 5 dimensions scored on a 5-Likert scale and visual analogue scale (0 to 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)
Other	Patient specific questionnaire	Self-administered questions about: gender, ethnicity, age, nationality, weight, height, civil state, mutuality, educational level, year of the breast cancer diagnosis, received breast cancer treatments, lymphedema, medication, other treatments, menopausal, hot flashes.	T1: baseline (within one week before randomisation)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)