Predicting, Understanding and Speeding Recovery After TKA

NCT02685735 | Terminated Phase 4 Results DMC FDA Drug

• 2 other identifiers: IRB000325065P01GM113852
• Study Type: interventional
• Target: 350
• Locations: 1 country
• Sites: 1

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.

Conditions

Pain; Total Knee Replacement; Total Hip Replacement

Outcome Measures

Primary Outcomes (3)

• Comparison of Adjusted Trajectory Model for Pain Between Gabapentin and Placebo--Intercept

  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.

  The first day after hospital discharge up to 5 days post surgery

• Comparison of Adjusted Trajectory Model for Pain Between Gabapentin and Placebo-- Slope

  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.

  Postoperative Day 1 through Postoperative Day 60

• Effect Pupil Diameter, Catastrophizing-optimism Construct, and Gabapentin on Model Fit of the Trajectory of Change in Worst Daily Pain After Surgery

  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.

  Postoperative Day 1 through Postoperative Day 60

Secondary Outcomes (3)

• Wisconsin Card Sort Task

  Preoperative, 2 months after surgery, 6 months after surgery

• Iowa Gambling Task

  Preoperative, 2 months after surgery, 6 months after surgery

• Tampa Scale of Kinesiophobia

  Preoperative, 2 months after surgery, 6 months after surgery

Other Outcomes (2)

• Biomarkers of Stress

  Preoperative

• Biomarkers of Noradrenergic Functioning

  Preoperative

Study Arms (2)

Gabapentin

ACTIVE COMPARATOR

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.

Drug: Gabapentin

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Gabapentin DRUG

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.

Also known as: neurontin

Gabapentin

Placebo DRUG

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.

Also known as: Inert ingredient

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• National Institute of General Medical Sciences (NIGMS): collaborator

Study Sites (1)

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

MeSH Terms

Conditions

Pain

Interventions

Gabapentin; Excipients

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Amines; Organic Chemicals; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Amino Acids; Amino Acids, Peptides, and Proteins; Pharmaceutical Vehicles; Pharmaceutic Aids; Pharmaceutical Preparations; Specialty Uses of Chemicals; Chemical Actions and Uses

Limitations and Caveats

Early termination leading to 240 rather than 250 participants analyzed.

Results Point of Contact

• Title: Dr. James Eisenach
• Organization: Wake Forest University School of Medicine

jimeisenach@gmail.com

336-716-4182

Study Officials

• James C Eisenach, MD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2015
• First Posted: February 19, 2016
• Study Start: June 2, 2016
• Primary Completion: February 9, 2022
• Study Completion: February 9, 2022
• Last Updated: August 15, 2025
• Results First Posted: October 4, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)