Chronic Postsurgical Pain, Postoperative Cognitive Dysfunction and Resilience (ArthroCaP)

A Prospective Cohort Study Exploring the Associations Between Chronic Postsurgical Pain and Postoperative Cognitive Dysfunction After Elective Knee or Hip Arthroplasty

"Brain damage" and "memory loss" are main concerns of people undergoing surgery. In fact, many older people undergoing different types of non-cardiac surgeries (including orthopedic surgeries) present a significant decline in their cognition (i.e. the way people use their brain to think, take action, make decision, and remember) 1 year after surgery. This is called postoperative cognitive dysfunction (POCD), and is significantly more frequent (as many as 30% of patients aged 65 or older) than what we would expect in non-surgical patients with similar age and comorbidities. Causes and mechanisms of POCD are poorly understood. Pain after surgery is also very frequent and can persist for a long time (i.e. persistent postsurgical pain, PPSP), requiring chronic medications including narcotics. Knee surgery is more often offered as a treatment in older patients with osteoarthritis, who often come to surgery after a long history of pain and impaired mobility, and who often experience PPSP. The investigators proposed to conduct a study in 200 people 55 years old or older (expected age range 55-85) who are undergoing their elective knee surgery, to evaluate the association between PPSP (and its treatment) and POCD. How cognition can interfere with resilience (coping strategies and expectations), which are also thought to influence the persistence of pain, satisfaction, and functional recovery after surgery, will also be explored. Patients will be enrolled before their surgery and followed over time, to collect data on their social and clinical characteristics, measure copying/expectations before and after surgery, and assess pain and pain medications, satisfaction and functional recovery, and cognitive performance. The study will also explore hypotheses of possible mechanisms underlying the association between PPSP and POCD, and will include interviews with a subset of the participants to explore lived experiences of pain, mobility and aging, including resilience, expectations and satisfaction with surgery.

Study Overview

• Status: Recruiting
• Conditions: Satisfaction, Patient; Postoperative Cognitive Dysfunction; Chronic Post Operative Pain; Coping Behavior

Detailed Description

The specific study objectives are to: 1- explore the association of CPSP, pain management (opioid use), and patient satisfaction, with postoperative cognitive dysfunction (POCD), measured both as change in the Montreal Cognitive Assessment (MoCA), and through a neuropsychological test battery, 2- explore whether postoperative cognitive changes are associated with changes in neurogenesis correlates and in neurotrophic factors levels, and whether this association is mediated by changes in pain, mobility, and satisfaction, and 3- explore the association between coping strategies/expectations as measured by the Somatic Preoccupation and Coping (SPOC) questionnaire and cognitive function, and in particular the relationship between changes in SPOC and cognitive changes from preoperative to 4-6 weeks after surgery.

Investigators will recruit 150 patients, 50 years or older scheduled for knee or hip arthroplasty 1-2 weeks before surgery (baseline) and collect information about their socio-demographics data, comorbidities, frailty, anxiety, pain, and pain medications. The SPOC questionnaire is administered at baseline and repeated at 4-6 weeks after surgery. CPSP (presence and severity) and satisfaction with surgery are measured at 3, 6, and 12 months. Cognitive / neuropsychological assessments will be administered at baseline, and 4-6 weeks, 6 months, and 12 months after surgery. Blood samples for serum and RNA expression analysis of biomarkers will be longitudinally collected with the same timeline.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Maura Marcucci, MD; Phone Number: 40594 9055274322; Email: marcum2@mcmaster.ca
• Study Contact Backup: Name: Maram Khaled, MBBCh, MSc; Phone Number: 9059220293; Email: khalem3@mcmaster.ca

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8S 4L8
      • Recruiting
      • McMaster University
      • Contact: Maura Marcucci, MD; Phone Number: 40594 9055274322; Email: marcum2@mcmaster.ca
      • Contact: Maram Khaled, MBBCh, MSc; Phone Number: 9059220293; Email: khalem3@mcmaster.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients 50 years or older undergoing elective total knee arthroplasty (TKA) or total hip arthroplasty (THA) for osteoarthritis

Description

Inclusion Criteria:

1. aged 50 years or older,
2. scheduled for elective TKA or THA for osteoarthritis
3. able to provide informed consent.

Exclusion Criteria:

1. known history of dementia,
2. unavailability of tablet or computer with an internet connection for remote assessment,
3. patient unable to interact with a tablet or computer due to language, visual, or hearing impairment, or any severely limited mobility of the upper limb joints, OR
4. patient unable to understand spoken or written English.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of postoperative cognitive dysfunction (binary outcome)	defined as a >=2 point decline in MoCA scores.	6 and 12 months postoperative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the Mnemonic Similarity Test scores	Participants are first engaged in an encoding phase then a subsequent recognition test with a 3-choice response; exact repetitions of earlier items, lures (similar but not identical to earlier items), and novel foils. During the test, participants are asked to identify each item as "Old," "Similar," or "New". The lure discrimination index (which measures mnemonic discrimination) is calculated as the difference between the rate of "Similar" responses given to the lure items minus "Similar" responses given to the foils. Typically, 'normal' aging is associated with a decline in mnemonic discrimination (identifying lure objects that are similar to memory set objects as "similar") with preserved recognition memory (identifying repeated memory set objects as "old"). The MST version used in the study is a validated modified online version of MST adapted to increase the efficiency of the test.	4-6 weeks and 6 and 12 months
Changes in the Visual Paired Associates Learning (PAL) test	A computer task that assesses visual memory and new learning by testing a participant's memory for object location pairs. Boxes are displayed on the screen and are opened in a randomized order. One or more of them will contain a pattern. The patterns are then displayed in the middle of the screen, one at a time, and the participant must touch the box where the pattern was originally located. If the participant makes an error, the patterns are represented by their locations. The difficulty increases throughout the test. The average accuracy across the last two completed levels will be analyzed	4-6 weeks and 6 and 12 months
Changes in the Rapid serial Visual Presentation (RVP) test	A white box is shown in the centre of the screen, inside which digits from 2 to 9 appear in a pseudo-random order, at the rate of 100 digits per minute. Participants are requested to detect target sequences of digits (for example, 2-4-6, 3-5-7, 4-6-8). When the participant sees the target sequence they must respond by selecting the button in the centre of the screen as quickly as possible. The level of difficulty varies with either one- or three-target sequences that the participant must watch for at the same time. The average accuracy throughout the task will be analyzed.	4-6 weeks and 6 and 12 months
Changes in the Stroop color word color interference task CWIT	CWIT has the standard color naming, word reading, and color-word interference trials,in addition to additional trial requiring the examinee to switch between inhibitory and non-inhibitory responses. Process measures enable assessment of general difficulties. Condition 1: Color Naming, Condition 2: Word Reading, Condition 3: Inhibition, Condition 4: Inhibition/ Switching requires adequate naming speed, reading speed, verbal inhibition, and cognitive flexibility.and Scores will include the time needed to complete each condition, the number of errors and the number of self-corrected errors	4-6 weeks and 6 and 12 months
Changes in the N-back test	Participants are shown a series of numbers on the screen and are asked to enter the number they saw two numbers ago. The outcome measures are correct detection and reaction times.	4-6 weeks and 6 and 12 months

Collaborators and Investigators

• Sponsor: McMaster University
• Collaborators: The McMaster Institute for Research on Aging (MIRA); Michael G. DeGroote Institute for Pain Research and Care (IPRC)
• Investigators: Principal Investigator: Maura Marcucci, MD, McMaster University

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2021
• Primary Completion (Anticipated): April 30, 2023
• Study Completion (Anticipated): July 31, 2024

Study Registration Dates

• First Submitted: October 28, 2022
• First Submitted That Met QC Criteria: November 10, 2022
• First Posted (Actual): November 14, 2022

Study Record Updates

• Last Update Posted (Actual): November 14, 2022
• Last Update Submitted That Met QC Criteria: November 10, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Total knee arthroplasty; Older adults; Total hip arthroplasty; Postoperative cognitive dysfunction; chronic postsurgical pain
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Neurocognitive Disorders; Cognition Disorders; Pain, Postoperative; Cognitive Dysfunction; Postoperative Cognitive Complications
• Other Study ID Numbers: 13598 (Company Internal)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No