Predicting, Understanding and Speeding Recovery After TKA

Wake Forest University (WFU)

Status and phase: Terminated; Phase 4

Conditions: Total Hip Replacement; Pain; Total Knee Replacement

Treatments: Drug: Placebo; Drug: Gabapentin

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02685735

5P01GM113852 (U.S. NIH Grant/Contract)

IRB00032506

Details and patient eligibility

About

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.

Full 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.

Enrollment: 350 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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350 participants in 2 patient groups, including a placebo group

Gabapentin

Active Comparator group

Description:

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.

Treatment:

Drug: Gabapentin

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo