Effect of Perioperative CBT on Chronic Persistent Postsurgical Pain Among Breast Cancer Patients

NCT ID: NCT04924010

Last Updated: 2023-03-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

48 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-05-31

Study Completion Date

2023-03-02

Brief Summary

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Chronic persistent post-surgical pain (CPSP) is defined as pain at or near the site of surgery persisting for 3 months or more after the date of surgery. The incidence CPSP in Europe is up to 50% at 3 months and 12% at 12 months, but the incidence varies depending on surgical procedure \[Fletcher D et al\]. In Breast surgery, one of the most commonly performed surgical procedures for cancer \[Kehlet H et al\], CPSP has been observed in 20-30% of patients at 6 months after surgery, making this group among the highest risk of developing CPSP \[Spivey TL et al \& Weiser TG et al\]. Clinical developments that could mitigate the development of CPSP after breast cancer surgery would potentially yield multiple benefits in terms of reducing future healthcare utilization, associated costs \[Spivey Tl et al\], and improving their physical and mental health.

Several predictive factors for CPSP have been identified, the most important being chronic pre-operative pain, high intensity of acute postoperative pain, and several psychological factors \[Vranceanu A-M et al\]. Of these psychological factors, pain catastrophizing has emerged as one of the strongest predictors of pain severity and disability among individuals with a range of pain presentations and CPSP \[Leung L \& Wade Jb \& Wildeman TH\]. Catastrophizing is described as a maladaptive psychological coping strategy involving an exaggerated reaction to anticipated or actual pain. It can involve mental rumination, magnification of the perceived danger or threat associated with pain, and feelings of helplessness in relation to what can be done \[Leung L et al\]. A recent systematic review on psychological interventions undergoing major elective abdominal surgery concluded catastrophization can have a direct influence on the neuropathophysiological mechanisms underlying pain experiences and can improve pain and psychological outcomes, after surgery \[Villa G et al\].

In recent years, there has been a growing number of studies investigating the potential impact of perioperative psychological interventions in a variety of patient groups. A recent systematic review and meta-analysis of observational studies concluded that psychological predictors may have a significant association with chronic postsurgical pain, including catastrophization, although this conclusion is limited by the heterogeneity of study designs and methods used \[Giusti et al\]. To our knowledge, no randomized controlled trial has been done to date, investigating the influence of perioperative psychological interventions on CPSP in patients undergoing breast cancer surgery.

Detailed Description

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This will be a single-center, prospective, double-blinded, randomized controlled trial. The study will randomize breast cancer surgery patients into two groups: one that receives perioperative cognitive-behavioral therapy (CBT) in addition to usual care and the other receives an educational program. The estimated duration for the main investigational plan (e.g. from the start of screening of the first participant to the last participant processed and finishing the study) is one year.

Aims and objectives:

The primary objective is to examine whether a perioperative CBT-based psychological intervention is effective at reducing pain intensity at three-month follow-up, in high catastrophizing patients undergoing breast cancer surgery, compared to an education program.

Secondary objectives of the study include examining whether perioperative CBT has a demonstrable impact on patients, compared to a time-matched education program, with regard to additional self-reported secondary outcomes, including quality-of-recovery, pain catastrophizing, pain interference, depression, and anxiety.

Participants and recruitment:

Adult patients who are undergoing breast surgery (defined as wide excision with magseed surgery or full mastectomy patients with or without axillary clearance) who are proficient in the English language will be eligible for inclusion. Patients will be enrolled at the outpatient clinic of the Department of Anaesthesiology and the Breast Health Department at the Mater Misericordiae University Hospital. All patients entering the screening phase of the study will be registered on a Study Patient Registration Log and a unique registration number will be assigned. Clinical data will be assessed to evaluate a subject's eligibility.

Patients eligible for participation will be evaluated approximately two weeks before surgery and asked for informed consent, and then asked to complete the Pain Catastrophizing Scale (PCS) \[Sullivan M et al\] by a member of the research team. Patients with high pain catastrophizing, defined as a score of ≥24 on the PCS, will be eligible for randomization to perioperative treatment with CBT or the education and mindfulness program. This cut-off is based on a previous study that showed a pre-treatment score of 24 or higher on the PCS best-predicted follow-up chronic pain ratings and work status after multidisciplinary treatment\[Scott W et al\] and has since been selected as an appropriate score cut-off in a perioperative CBT intervention in lumbar surgery patients \[Scarone P et al\]. More recently, this cut-off was also suggested to obtain the highest sensitivity and specificity to predict unfavorable outcomes after spinal surgery \[Tuna T et al\].

Randomization:

Patients will be randomized after they are included in the study, having consented and completed the PCS (and scoring scored ≥24), and two preoperative appointments will be scheduled with the patients in the intervention and control groups. Patients will be randomized to either 'CBT' or 'Education' group by using an online computer-generated block randomization. The patient study number and group allocation will be typed onto separate pages and concealed in sequentially numbered sealed envelopes. Block randomization will occur as follows; 12 subjects per block to ensure even numbers of participants in each arm of the study and the number of blocks that will be used is 4. Randomization will be performed by an independent third party. The randomization key/seed will also be held by an independent third party and investigators will not have access to this key/seed until the study has been completed.

The envelope will be opened by the treating psychologist to reveal the group allocation. Patients and members of the research team involved in data collection and analyzing the data will be masked to group allocation. The treating psychologist will not be blinded. Group allocations will be revealed immediately if there was a clinical concern.

All patients in both interventional arms:

All patients, irrespective of group allocation, will be routinely prescribed medications for pain control and will be referred for physical therapy on an out-patient basis, or other services, depending on clinical indications and personal needs.

Sample size, power considerations, and statistical analysis:

The primary outcome is the difference in the BPI average pain severity score and average pain interference score between the study groups, three months after surgery. A clinically important difference on the BPI is a 2 raw score reduction on the 11-point NRS \[Wong K et al \& Marcus J et al \& Mease PJ etl al\]. The standard deviation (SD) of BPI scores after breast surgery is in the order of 2.3 on this scale (Burckhardt CS et al). Taking a BPI score reduction of 2 as being clinically significant, then n=21 patients would be required each arm if Type I error=0.05 and Type II error is 0.2 (power 80%). Taking into account a 10% drop-outs rate, we propose to enroll 24 eligible patients in each group (N=48 total).

Baseline patient characteristics will be stratified by group and presented as mean and standard deviation (SD), median and first and third quartile, and count and percentage, as appropriate. Differences in baseline characteristics between randomized groups will not be statistically tested, whereas differences with the separate control cohort will be tested using the independent-samples t-test for continuous variables, and Pearson's chi-square test for categorical variables. In case of expected cell counts of less than 5, Fisher's Exact test will be used instead.

All patients randomized (i.e. those with a PCS score \> 24) will be analyzed in an intention-to-treat analysis. To test for a difference between the CBT and control group in the BPI 'average' pain intensity scale at three months, linear regression will be used. Adjustment for the type of surgery, age, and education will be made and, if necessary, for other prognostic variables significantly associated with the outcome (i.e., acute postoperative pain intensity, the severity of catastrophizing, preoperative depression, preoperative surgical fear, length of current sick leave, pain duration).

Secondary outcome variables will be analyzed similarly to the primary outcome. For these, logistic regression analysis will be used to test for differences in proportions at three months postoperatively. For exploratory purposes, we will compare the outcomes of the patients in the two intervention groups with the outcomes of patients with low pain catastrophizing scores (i.e. those with a PCS score \< 24) undergoing care as usual. Linear mixed-effects regression for the three groups will be performed with primary and secondary outcomes at the three postoperative assessment periods and controlling for preoperative values. This analysis will indicate whether high catastrophizing patients follow a similar trajectory of pain and functioning after breast surgery compared to non-catastrophizing patients.

Conditions

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Breast Cancer Chronic Pain Chronic Postsurgical Pain Quality of Life

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors
Patients will be blinded to which intervention they will receive. The outcome assessors for this study will be unaware as to which group the participant will be randomised to and therefore they will be blinded to which intervention the participant had received

Study Groups

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Cognitive Behavioural Therapy (CBT)

Cognitive behavioural therapy (CBT) is a talking therapy that can help patients manage problems by changing the way they think and behave. It's most commonly used to treat anxiety, depression and chronic pain conditions.

Group Type ACTIVE_COMPARATOR

Cognitive Behavioural Therapy (CBT)

Intervention Type BEHAVIORAL

The CBT intervention will be delivered by a Senior Psychologist with seventeen years of hospital psychology experience, six in the treatment of chronic pain patients. Sessions are delivered in one hour, individual therapy appointments to patients, and there is an emphasis on relaxation training, cognitive restructuring, exercise and pacing, behavioral activation, improving sleep, and anger management. Standardized worksheets and homework assignments are an important part of CBT-CP and these will be given (post or email) to patients who will be asked to read and complete in terms of complementing the consultations. This intervention has been developed with reference to two sources: A successful national implementation of CBT for chronic pain (CBT-CP) using video teleconferencing format \[Connolly KS et al\] AND an evidence-based CBT manual specifically designed to treat chronic pain \[Murphy JL et al\].

Education and Mindfulness

Education and mindfulness therapy refers to lessons on techniques to calm the mind and body - can reduce the negative effects of stress

Group Type PLACEBO_COMPARATOR

Education and Mindfulness

Intervention Type BEHAVIORAL

To control for differences in attention between the two interventions, patients in the mindfulness group will also have two meetings before the surgery and two meetings afterward. As the same person will be providing the CBT-CP and educational interventions, this confounding factor will be controlled for. The control intervention consists of discussing pain education, as derived from the self-management section of the chronic pain Ireland website (https://www.chronicpain.ie/our-services/self-management) and the persistent pain section of the pain toolkit website (https://www.paintoolkit.org/persistent-pain). Four mindfulness-based stress reduction exercises will be completed including an introductory session on mindful breathing, a guided meditation, progressive muscle relaxation, and a body scan. These sessions will last about half an hour.

Interventions

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Cognitive Behavioural Therapy (CBT)

The CBT intervention will be delivered by a Senior Psychologist with seventeen years of hospital psychology experience, six in the treatment of chronic pain patients. Sessions are delivered in one hour, individual therapy appointments to patients, and there is an emphasis on relaxation training, cognitive restructuring, exercise and pacing, behavioral activation, improving sleep, and anger management. Standardized worksheets and homework assignments are an important part of CBT-CP and these will be given (post or email) to patients who will be asked to read and complete in terms of complementing the consultations. This intervention has been developed with reference to two sources: A successful national implementation of CBT for chronic pain (CBT-CP) using video teleconferencing format \[Connolly KS et al\] AND an evidence-based CBT manual specifically designed to treat chronic pain \[Murphy JL et al\].

Intervention Type BEHAVIORAL

Education and Mindfulness

To control for differences in attention between the two interventions, patients in the mindfulness group will also have two meetings before the surgery and two meetings afterward. As the same person will be providing the CBT-CP and educational interventions, this confounding factor will be controlled for. The control intervention consists of discussing pain education, as derived from the self-management section of the chronic pain Ireland website (https://www.chronicpain.ie/our-services/self-management) and the persistent pain section of the pain toolkit website (https://www.paintoolkit.org/persistent-pain). Four mindfulness-based stress reduction exercises will be completed including an introductory session on mindful breathing, a guided meditation, progressive muscle relaxation, and a body scan. These sessions will last about half an hour.

Intervention Type BEHAVIORAL

Eligibility Criteria

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Inclusion Criteria

* Female patients
* 18-75 years of age
* Undergoing breast cancer surgery (wide local excision with magseed or full mastectomy)
* Pain Catastrophizing Scale score of 24 of higher

Exclusion Criteria

* Pain Catastrophizing Scale score below 24
* Surgery for benign breast disease
* Patient non-consent
* Plans to undergo major surgery within six months after current breast surgery
* Comorbid severe psychiatric conditions such as schizophrenia or personality disorder
* Known or suspected non-compliance
* Known or suspected drug or alcohol abuse problems within past 3 months
* Inability to follow the study procedures e.g. dementia or non-fluency of English
* The presence of any serious medical comorbidity such as sepsis or cancer that might cause disability or worsen the patient's general health condition
* Pregnancy
* An opioid intrathecal pump
* Prisoner within the criminal justice system
* Cognitive behavioural therapy in the past 12 months
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Mater Misericordiae University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Aneurin Moorthy

Research Fellow in Anaesthesia and Perioperative Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Donal Buggy, MB Bch BAO

Role: PRINCIPAL_INVESTIGATOR

Department of Anaesthesiology & Perioperative Medicine, Mater Misericordiae University Hospital,

Locations

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Mater Misericordiae University Hospital

Dublin, , Ireland

Site Status

Countries

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Ireland

References

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Fletcher D, Stamer UM, Pogatzki-Zahn E, Zaslansky R, Tanase NV, Perruchoud C, Kranke P, Komann M, Lehman T, Meissner W; euCPSP group for the Clinical Trial Network group of the European Society of Anaesthesiology. Chronic postsurgical pain in Europe: An observational study. Eur J Anaesthesiol. 2015 Oct;32(10):725-34. doi: 10.1097/EJA.0000000000000319.

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Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and prevention. Lancet. 2006 May 13;367(9522):1618-25. doi: 10.1016/S0140-6736(06)68700-X.

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Spivey TL, Gutowski ED, Zinboonyahgoon N, King TA, Dominici L, Edwards RR, Golshan M, Schreiber KL. Chronic Pain After Breast Surgery: A Prospective, Observational Study. Ann Surg Oncol. 2018 Oct;25(10):2917-2924. doi: 10.1245/s10434-018-6644-x. Epub 2018 Jul 16.

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Related Links

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https://doi.org/10.1007/s41347-017-0024-4

Nationwide implementation and outcomes of cognitive behavioral therapy for chronic pain over clinical video teleconferencing. J Technol Behav Sci

https://www.va.gov/painmanagement/docs/cbt-cp_therapist_manual.pdf

Cognitive behavioral therapy for chronic pain among veterans: therapist manual. Washington, DC: Department of Veterans Affairs

https://www.chronicpain.ie/our-services/self-management

Pain education, self-management section of the chronic pain Ireland

Other Identifiers

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CBTMMUH

Identifier Type: -

Identifier Source: org_study_id

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