Opioid Induced Loss of Local Anesthetic Potency in Patients Undergoing Total Knee Arthroplasty

NCT03294174 | Terminated

• 1 other identifier: PRO15020146
• Study Type: observational
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

Peripheral nerve blocks with local anesthetics (LAs) have become an integral part of postoperative pain management particularly for patients undergoing major limb procedures such as such as Total Knee Arthroplasty (TKA). And while postoperative pain management in patients with a history of chronic opioid use may be difficult with systemic opioids because of opioid tolerance, there is anecdotal evidence suggesting that these patients may also be less responsive to LAs. Preliminary data from pre-clinical animal study show that there is a decreased LA potency in blocking sciatic nerve in opioid tolerant rats. And the decrease in LA potency is reversed by the knock-down of the beta4 subunits of Voltage-gated sodium channels along the sciatic nerves, suggesting the opioid induced intrinsic changes in the peripheral nerve as an underlying mechanism for opioid induced loss of LA potency. Study Goals: To determine the extent to which the changes in beta4 subunits of voltage-gated sodium channels are reflected in surgical patients. Experimental Design / methodology: This is a prospective, double-blind, active treatment controlled study. TKA Patients who receive nerve blocks will be grouped according to their history of pre-operative opioid use, and then tested for local anesthetic use for nerve block. Synovial tissues will also be collected for the analysis of beta4 subunits. Subject population: Patients who are scheduled for TKA procedure, and agree to receive peripheral nerve block for postoperative pain control, will be recruited for the study. Patients will participate in one of the three study groups: opioid naive, opioid history and opioid tolerant. 30 patients for each group with a total of 90 patients will be recruited. This study will not only determine the extent to which the preclinical findings are reflected in clinical patients, but also identify the underlying mechanisms that may suggest strategies for more effective post-operative pain management in the growing population of opioid tolerant patients

Conditions

Opioid Tolerance, Opioid Naive, Opioid Exposure

Outcome Measures

Primary Outcomes (1)

• Sensory and motor function loss after nerve block procedures

  Sensory block is assessed by evaluating the presence and absence of response to thermal stimulation applied to the central sensory region of the blocked nerve, using Medoc 5x5 thermode (see details in description)

  within first 30 min

Secondary Outcomes (2)

• pain

  within 1 hour

• sodium channel subunit changes in synovial tissues

  Synovial tissues will be extracted within 1 hour after nerve block. Western blotting techniques will be used to quantify the changes in sodium channel subunit level

Study Arms (3)

Opioid naive

Patients who have not been exposed to opioids, but will receive ropivacaine injection

Drug: Ropivacaine injection

Opioid exposure

Patients who have been exposed to(\> 6months), but not currently taking opioids, but will receive ropicacaine injection

Drug: Ropivacaine injection

opioid tolerance

Patients who have been actively taking opioids with a tolerant dose based on FDA guideline, but will receive ropivacaine injection

Drug: Ropivacaine injection

Interventions

Ropivacaine injection DRUG

Ropivacaine administered to provide nerve block

Also known as: ropivacaine nerve block

Opioid exposure; Opioid naive; opioid tolerance

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Participants of the study will belong to one of the three groups: opioid naive, opioid history (those with a history of opioid use, but who are not currently on opioids) and opioid tolerant (those using opioids at the time of surgery)

You may qualify if:

• American Society of Anesthesiologists Classification 1,2 and 3;
• Age between 18-80;
• Both males and females of all races
• Receive total knee arthroplasty (TKA)
• Agree to receive peripheral nerve blocks for postoperative pain control
• Participants of the study will belong to one of the three groups: opioid naive, opioid history (those with a history of opioid use, but who are not currently on opioids) and opioid tolerant (those using opioids at the time of surgery)

You may not qualify if:

• Intolerance and/or known allergy to opioids and/or LAs;
• TKA due to trauma;
• Use of general anesthesia for the operation

Sponsors & Collaborators

• University of Pittsburgh: lead

Study Sites (1)

University of Pittsburgh

Pittsburgh, Pennsylvania, 15206, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Synovial tissues will be collected from each study patient

MeSH Terms

Interventions

Ropivacaine

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2016
• First Posted: September 26, 2017
• Primary Completion: June 1, 2017
• Study Completion: June 1, 2017
• Last Updated: November 9, 2018

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will share

Locations

US (1)