Clinical trial NCT03965897: Preventing Persistent Post-Surgical Pain and Dysfunction
Official title: Preventing Persistent Post-Surgical Pain and Dysfunction in At-Risk Veterans: Effect of a Brief Behavioral Intervention
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pain
Function
Anxiety
Depression
Arthroplasty, Replacement, Knee
Veterans
Lead sponsor: University of Iowa
Sponsor class: OTHER
Collaborators: name: Baylor College of Medicine
name: National Institute of Nursing Research (NINR)
name: Iowa City Veterans Affairs Medical Center
First posted: 2019-05-29
Enrollment: 487
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study uses a cluster randomization approach where the unit of randomization is the workshops. Randomization occurs at the start of each workshop so that all participants attending that workshop are randomized to that intervention (i.e. ACT vs. AC). Statistician Dr. Zimmerman generates the randomization sequence using PLAN procedure (SAS v9.2). Randomization of workshops occurs in permuted blocks of 2 and 4 and are stratified by site (i.e. Iowa City versus Houston).
Primary purpose: PREVENTION

Brief summary: Primary Aim: To examine the superior efficacy of ACT versus Attention Control (AC) on postoperative pain intensity and functioning in at-risk Veterans undergoing TKA. Changes in pain intensity and functioning from baseline to 6 weeks, 3 months and 6 months post-TKA will be compared. Level of pain intensity will be measured using the BPI Pain Severity Subscale and level of functioning will be measured using the KOOS Activities of Daily Living and Quality Of Life Subscales.

Secondary Aims: A) To examine the superior efficacy of ACT versus AC on the severity of anxiety and depressive symptoms and improvements in coping skills. Changes from baseline to 6 weeks, 3 months and 6 months post-TKA will be compared. Anxiety and depressive symptoms will be measured with the Hamilton Rating Scales (Ham-A and Ham-D, respectively). Coping skills (i.e. Pain Acceptance and Engagement in Values-Based Behavior) will be measured with the Chronic Pain Acceptance Questionnaire and the Chronic Pain Values Inventory. B) To evaluate whether decreases in distress-based symptoms and increases in coping skills mediate changes in pain and functioning at 6 months in Veterans receiving ACT. Changes in anxiety symptoms, depressive symptoms, pain acceptance and engagement in values-based behavior from baseline to 6 weeks and 3 months will be used as potential mediators for changes in pain and functioning at 6 months.

Exploratory Aim: Describe the pharmacological and non-pharmacological strategies Veterans are using to manage pain and their perceived helpfulness. This will provide insights into the effects of the current opioid restrictions on pain management strategies. These strategies \& their perceived helpfulness will be assessed using the Pain Management Strategies Survey at baseline, 6 weeks, 3, and 6 months.

Detailed description: Persistent post-surgical pain (PPSP) is a common and debilitating problem following surgery.1 Orthopedic surgeries, such as Total Knee Arthoplasty (TKA), are consistently associated with high postoperative pain, putting patients at risk for PPSP.2, 3 In fact, TKA has the highest rate of PPSP at 6 months (49%) when compared to a variety of surgeries.4 Pain that persists beyond the expected period of healing serves little or no useful purpose and can be devastating to one's sense of well-being. Notably, pain severity is highly correlated with adverse effects on physical functioning, recovery and quality of life, including negative impacts on sleep, mood, daily activities, cognitive functions and social life.2, 5-13 PPSP is also highly correlated with prolonged opioid use following surgery. When pain and addiction are present, the patient's level of desperation rises, medical and psychiatric illness severity increases, and there is greater utilization of health care services.

Strong and consistent evidence indicates that patients with high levels of pain, anxiety and/or depressive symptoms (distress) prior to surgery are at risk for PPSP.5, 14-23 Notably, Veterans are at a particularly high risk for post-surgical problems because 80% experience some level of psychological distress prior to surgery and 50% report experiencing pain on a regular basis.9, 24 Furthermore, surgery presents a unique set of circumstances in which the precise timing of the physical insult and ensuing pain are known in advance. 25 It is, therefore, possible and critical that these risk factors be attended to in order to improve postoperative pain management and disrupt processes responsible for the transition from acute to chronic pain.

As proof of concept, co-PIs Rakel and Dindo completed an R34-funded study evaluating the feasibility and potential efficacy of an intensive 1-day Acceptance and Commitment Therapy (ACT) workshop for preventing PPSP and prolonged opioid use following orthopedic surgery in at-risk Veterans. ACT is trans-diagnostic, with effectiveness across a range of conditions, including chronic pain, depression, and anxiety.16-18 The brief, 1-day format was used to optimize treatment adherence and chances for dissemination into clinical settings. Results were promising. 100% of the Veterans attending, completed the 1-day intervention. Compared to controls, Veterans randomly assigned to ACT reported a larger decrease in pain intensity 3 months post-TKA and reached pain and opioid cessation criteria sooner. Importantly, Veterans reporting larger changes in behavioral engagement (targeted mediator of ACT) exhibited significantly larger decreases in pain and opioid use. This application builds on these promising preliminary findings using a rigorous design to establish the unique effects of ACT beyond attention and explore mediators of treatment response.

In the context of the current opioid epidemic, it is also important for us to better understand how changes in opioid prescribing patterns are influencing postoperative pain management strategies. It is likely that complaints of pain will increase, putting patients at higher risk for PPSP and impaired functioning. Early reports suggests that patients are looking for substitute sources of pain relief, such as rogue Fentanyl powder and Gabapentin.26, 27 Using a multi-site, double-blind, two-arm, parallel, randomized controlled trial with Veterans at-risk for PPSP post-TKA, the following aims will be addressed:

Primary Aim: To examine the superior efficacy of ACT versus Attention Control (AC) on postoperative pain intensity and functioning in at-risk Veterans undergoing TKA. Changes in pain intensity and functioning from baseline to 6 weeks, 3 months and 6 months post-TKA will be compared. Level of pain intensity will be measured using the BPI Pain Severity Subscale and level of functioning will be measured using the KOOS Activities of Daily Living and Quality Of Life Subscales.

Secondary Aims: A) To examine the superior efficacy of ACT versus AC on the severity of anxiety and depressive symptoms and improvements in coping skills. Changes from baseline to 6 weeks, 3 months and 6 months post-TKA will be compared. Anxiety and depressive symptoms will be measured with the Hamilton Rating Scales (Ham-A and Ham-D, respectively). Coping skills (i.e. Pain Acceptance and Engagement in Values-Based Behavior) will be measured with the Chronic Pain Acceptance Questionnaire and the Chronic Pain Values Inventory. B) To evaluate whether decreases in distress-based symptoms and increases in coping skills mediate changes in pain and functioning at 6 months in Veterans receiving ACT. Changes in anxiety symptoms, depressive symptoms, pain acceptance and engagement in values-based behavior from baseline to 6 weeks and 3 months will be used as potential mediators for changes in pain and functioning at 6 months.

Exploratory Aim: Describe the pharmacological and non-pharmacological strategies Veterans are using to manage pain and their perceived helpfulness. This will provide insights into the effects of the current opioid restrictions on pain management strategies. These strategies \& their perceived helpfulness will be assessed using the Pain Management Strategies Survey at baseline, 6 weeks, 3, and 6 months.

This project builds on promising preliminary data and has the potential to translate what is known about effective treatments of chronic pain to prevent poor surgical outcomes. It incorporates an interdisciplinary approach to the care of Veterans that attends to major risk factors of postoperative sequelae that significantly impact Veterans' quality of life and healthcare utilization. Using an effective, highly accepted and deployable intervention increases the clinical usefulness of these results which may be extended in the future to the many other conditions leading to chronic pain in both Veterans and Civilians.

Eligibility criteria: Inclusion Criteria:

* scheduled for unilateral total knee arthroplasty (TKA)
* identified to be "at-risk" at the enrollment visit (i.e. worst pain ≥7 on BPI (severe pain) OR worst pain ≥3 (moderate pain) on BPI PLUS anxiety symptoms ≥6 on the Anxiety Subscale of the Depression, Anxiety and Stress Scale \[DASS-21\] or ≥10 on the Stress Subscale of the Depression, Anxiety and Stress Scale \[DASS-21\] OR depressive symptoms ≥7 on Depression Subscale of the Depression, Anxiety and Stress Scale \[DASS-21\] OR \>20 on the Pain Catastrophizing Scale \[PCS\].

Exclusion Criteria:

* inability to complete study forms/procedures because of a language/literacy barrier;
* bipolar or psychotic disorder
* history of brain injury
* cognitive impairment (determined by score of \<21 \[high school or above\] or \<20 \[\< high school\] on the Veterans Affairs Saint Louis University Mental Status \[SLUMS\] exam)
* ACT therapy within the past year
* inability to attend workshop prior to surgery

Primary outcomes:
measure: Pain Intensity
timeFrame: Baseline (preop) to 6 months post-surgery.
measure: Function
timeFrame: Baseline (preop) to 6 months post-surgery
Secondary outcomes:
measure: Anxiety
timeFrame: Baseline (preop) to 6 months post-surgery
measure: Depressive Symptoms
timeFrame: Baseline (preop) to 6 months post-surgery
measure: Level of Pain Acceptance
timeFrame: Baseline (preop) to 6 months post-surgery
measure: Level of Success in Engagement in Values-Based Behavior
timeFrame: Baseline (preop) to 6 months post-surgery
measure: Pain Management Strategies used
timeFrame: Baseline (preop) to 6 months post-surgery
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: Iowa City VAMC
state: Iowa
Study officials:
affiliation: University of Iowa
name: Barbara Rakel, PhD
role: PRINCIPAL_INVESTIGATOR
References: