Predicting, Understanding and Speeding Recovery After TKA

Phase 4

Terminated

Conditions: Total Knee Replacement
Total Hip Replacement
Pain

Interventions: Drug: Placebo
Drug: Gabapentin

Registration Number: NCT02685735

Lead Sponsor: Wake Forest University Health Sciences

Brief Summary: The objective of this research study is to better understand patterns of recovery after Total Knee Arthroplasty (TKA) amd Total Hip Replacement (THA). The study will evaluate how pain, activity and cognitive (i.e., thinking style) responses determine patterns of recovery, and the study will evaluate the efficacy of gabapentin versus placebo for improving recovery after surgery.

Detailed Description: The investigators propose a two-site, longitudinal, double-blind, randomized clinical intervention study to examine three specific aims:

Aim 1: Characterize the dynamic pain experience, activity, and cognitive response after TKA and determine patterns of recovery in these domains

Aim 2: Test whether gabapentin alters time course of recovery after TKA or THA in a manner dependent on its interaction with pre-drug pupil diameter and preferred style in the catastrophizing-optimism dimension

Aim 3: Test whether gabapentin increases pupil diameter in patients undergoing TKA or THA who are on high dose opioids preoperatively and to examine whether opioid use moderates the associations in Aim 1

Primary Hypothesis: Novel variance beyond established associations in recovery from pain following TKA or THA surgery is accounted for by the interaction between pupil diameter and Cognitive-Affective (C-A) state, and this interaction predicts efficacy of gabapentin to speed recovery.

Key secondary hypotheses: Disability, impulsivity, and attentional deficits recover after TKA or THA surgery follow a log of time pattern, and are predicted by C-A state and its interaction with pupil diameter. Gabapentin increases resting pupil diameter in patients scheduled for TKA who are receiving high doses of opioids.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 350

Inclusion Criteria

Adults scheduled for elective total knee or hip replacement
American Society of Anesthesiologists physical status 1-3
Participants must be able to read and write English

Exclusion Criteria

Inability to complete questionnaires
Pregnancy
Litigation or workers compensation related to joint surgery
For 250 subjects in primary analysis - taking < 100 mg morphine equivalents/day. For 50 subjects to test gabapentin's effect on pupil diameter - taking >100 mg morphine equivalents/day
history of Raynaud's disease of the feet
suffering from a psychotic disorder or a recent psychiatric hospitalization
history of eye surgery or topical eye medications that would render pupillometry unreliable or would directly affect pupil diameter.
any disorder that would affect pupil responsivity or prevent accuracy of pupillometry such as movement disorders

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Subjects will be randomized, stratifying for norepinephrine serotonin reuptake inhibitor (NSRI) use, to equal number to receive gabapentin or placebo pills. Drug treatment will begin 2 weeks prior to surgery and continue 3 weeks afterwards.
Gabapentin	Gabapentin	Subjects will be randomized, stratifying for norepinephrine serotonin reuptake inhibitor (NSRI) use, to equal number to receive gabapentin or placebo pills. Drug treatment will begin 2 weeks prior to surgery and continue 3 weeks afterwards. Subjects randomized to gabapentin will receive 900 mg/day for the first week, 1800 mg/day for the next 3 weeks, and 900 mg/day for the last week.

Primary Outcome Measures

Name	Time	Method
Comparison of Adjusted Trajectory Model for Pain Between Gabapentin and Placebo--Intercept	The first day after hospital discharge up to 5 days post surgery	Daily pain intensity report for each subject was fitted using growth curve model with parameters of intercept (modeled initial pain) and slope of change in natural log of time, adjusted for prognostic predictors for gabapentin and placebo group separately. The daily pain intensity was the WORST pain (not the average pain) in the past 24 hr on a scale where 0 is no pain and 10 is worst imaginable pain. Values represent an intercept of modeled worst daily pain on the first day after hospital discharge across all participants, extracted from the mixed effect model. The intercept is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model.
Comparison of Adjusted Trajectory Model for Pain Between Gabapentin and Placebo-- Slope	Postoperative Day 1 through Postoperative Day 60	Daily pain intensity report for each subject was fitted using growth curve model with parameters of intercept (modeled initial pain) and slope of change in natural log of time, adjusted for prognostic predictors for gabapentin and placebo group separately. The daily pain intensity was the WORST pain (not the average pain) in the past 24 hr on a scale where 0 is no pain and 10 is worst imaginable pain. Slope is defined as change in pain . Values represent the slope of modeled worst daily pain (0-10 scale as described above) divided by the natural log of time (days) across all participants, extracted from the mixed effect model. The slope is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model.
Effect Pupil Diameter, Catastrophizing-optimism Construct, and Gabapentin on Model Fit of the Trajectory of Change in Worst Daily Pain After Surgery	Postoperative Day 1 through Postoperative Day 60	Daily pain intensity report for each subject was fitted using growth curve model, adjusted for pre-specified prognostic predictors . The daily pain intensity was the WORST pain (not the average pain) in the past 24 hr on a scale where 0 is no pain and 10 is worst imaginable pain. Deviance values were calculated from the model fit with just pre-specified prognostic predictors (Model 1) and the model fit with these predictors plus pupil diameter, catastrophizing-optimism construct, gabapentin treatment and their interaction. Deviance is a goodness-of-fit statistic for a statistical model; it is often used for statistical hypothesis testing. It is a generalization of the idea of using the sum of squares of residuals (SSR) in ordinary least squares to cases where model-fitting is achieved by maximum likelihood. Deviance ranges from 0 to infinity. The smaller the number the better the model fits the sample data. Model fits were compared using Chi-squared test.

Secondary Outcome Measures

Name	Time	Method
Iowa Gambling Task	Preoperative, 2 months after surgery, 6 months after surgery	This is a computer based card game which assesses risk taking and impulsivity in which a score of -100 to 100 is calculated. Lower numbers indicate greater impulsiivity
Tampa Scale of Kinesiophobia	Preoperative, 2 months after surgery, 6 months after surgery	This 17-question scale assesses the degree of fear of pain from joint movement and is commonly used in orthopedic injury or surgery studies. The scale ranges from 17 to 68 with 17 indicating no fear of movement and 68 indicating severe fear.
Wisconsin Card Sort Task	Preoperative, 2 months after surgery, 6 months after surgery	This is a physical card sorting game which measures attention to shifts in implicit rules as the game progresses. Perseverative errors are the number of sequential errors when rules of the game shift and reflect dysfunction of attention. This score ranges from 0 to 64 with larger numbers reflecting more dysfunction of attention.