Does Duloxetine Reduce Chronic Pain After Total Knee Arthroplasty?

Range from 24% to 44%, with a prevalence of neuropathic-type pain from 6% to 20%-cause impairment in quality of life and functional capacity after total knee arthroplasty(TKA). Duloxetine (cymbalta) is a selective serotonin and nor-epinephrine reuptake inhibitor shown to be effective in treating chronic pain. Serotonin and norepinephrine in the brain and spinal cord are believed to both mediate core mood symptoms and help regulate the perception of pain. Its effects on depression and anxiety symptoms, as well as its effect on pain perception, may be due to increasing the activity of serotonin and norepinephrine in the central nervous system. Approved for the acute and maintenance treatment of major depressive disorder, the acute treatment of generalized anxiety disorder, the management of diabetic peripheral neuropathic pain and the management of fibromyalgia, all in adults (18+).

Investigators will compare the neuropathic pain following TKA in duloxetine group (n=84) with those in non-duloxetine group (n=84). Investigators will classify the participants in to 2 groups (duloxetine and non-duloxetine group) randomly, and primarily evaluate the degree of neuropathic pain using the S-LANSS pain scale (preoperatively and postoperatively 3 and 6 months). All participants will receive postoperative pain control after TKA using the same pain control regimen except duloxetine.

Study Overview

• Status: Unknown
• Conditions: Neuropathic Pain
• Intervention / Treatment: Drug: Duloxetine; Drug: celecoxib, naproxen/esomeprazole, acetaminophen/tramadol, oxycodone/naloxone

Detailed Description

Both groups of participants will receive pain control regimens as follows:

Preemptive analgesia : celebrex celecoxib, Patient controlled analgesia (postoperation 28 hours), During admission : celebrex BP or vimovo BP +ultracet ER BP, targin HS, Discharge medication: celebrex BP or vimovo BP, ultracet ER BP(PRN)

Drug generic names: celecoxib (celebrex), naproxen/esomeprazole (vimovo), acetaminophen/tramadol (ultracet ER), oxycodone/naloxone (targin)

• Study Type: Interventional
• Enrollment (Anticipated): 168
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jinkyu Lee; Phone Number: +82-10-9582-7004; Email: gaia-silver@hanmail.net
• Study Contact Backup: Name: Changhoon Lee; Phone Number: +82-10-8635-6990; Email: toyessay@hanmail.net

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 133-792
    • Recruiting
    • Department of Orthopaedic Surgery, Hanyang University, College of Medicine
    • Contact: Jinkyu Lee; Phone Number: +82-10-9582-7004; Email: gaia-silver@hanmail.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Osteoarthritis of knee requiring TKA

Exclusion Criteria:

• Rheumatoid arthritis
• Other inflammatory arthritis
• Neuropsychiatric patients
• Hepatic insufficiency
• Renal insufficiency
• Patients older than 75
• Allergy or intolerance to study medications
• Patients with an ASA of IV (angina, congestive heart failure, dementia, cerebrovascular accident)
• Chronic gabapentin or pregabalin use (regular use for longer than 3 months)
• Chronic opioid use (taking opioids for longer than 3 months)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Duloxetin group; Phase I (preemptive): 2 hour before surgery (30mg for 1 day); Phase II (titration): POD#1~6 (30mg for another 6 days); Phase III (maintenance): POD#7~13(60mg for 7 days); Phase IV (tapering-1): POD#14~20 (30mg for 7 days); Phase V (tapering-2): POD#21~27 (30mg another every day for 7 days) plus routine pain control (celecoxib, naproxen/esomeprazole, acetaminophen/tramadol, oxycodone/naloxone)	Drug: Duloxetine; Phase I (preemptive): 2 hour before surgery (30mg for 1 day); Phase II (titration): POD#1~6 (30mg for another 6 days); Phase III (maintenance): POD#7~13(60mg for 7 days); Phase IV (tapering-1): POD#14~20 (30mg for 7 days); Phase V (tapering-2): POD#21~27 (30mg another every day for 7 days); Other Names: cymbalta; Drug: celecoxib, naproxen/esomeprazole, acetaminophen/tramadol, oxycodone/naloxone; Preemptive analgesia : celebrex, Patient controlled analgesia (postop. 28 hours), During admission : celebrex BP or vimovo BP +ultracet ER BP, targin HS, Discharge medication: celebrex BP or vimovo BP, ultracet ER BP(PRN); Other Names: celebrex, vimovo, ultracet, targin
Active Comparator: routine pain control group; Preemptive analgesia : celebrex, Patient controlled analgesia (postop. 28 hours), During admission : celebrex BP or vimovo BP +ultracet ER BP, targin HS, Discharge medication: celebrex BP or vimovo BP, ultracet ER BP(PRN) Other name of drugs: celecoxib, naproxen/esomeprazole, acetaminophen/tramadol, oxycodone/naloxone	Drug: celecoxib, naproxen/esomeprazole, acetaminophen/tramadol, oxycodone/naloxone; Preemptive analgesia : celebrex, Patient controlled analgesia (postop. 28 hours), During admission : celebrex BP or vimovo BP +ultracet ER BP, targin HS, Discharge medication: celebrex BP or vimovo BP, ultracet ER BP(PRN); Other Names: celebrex, vimovo, ultracet, targin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
neuropathic pain(the self assessed-Leeds Assessment of Neuropathic Symptoms and Signs pain scale, S-LANSS)	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Numeric rating scale for pain (NRS)	6 months
American Knee Society knee and function score	6 months
Western Ontario and McMaster University Arthritis Index (WOMAC)	6 months
Geriatric depression scale-short form	6 months

Collaborators and Investigators

• Sponsor: Hanyang University Seoul Hospital
• Investigators: Study Chair: Choonghyeok Choi, Hanyang University

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (Anticipated): December 1, 2016
• Study Completion (Anticipated): December 1, 2016

Study Registration Dates

• First Submitted: November 27, 2014
• First Submitted That Met QC Criteria: December 1, 2014
• First Posted (Estimate): December 4, 2014

Study Record Updates

• Last Update Posted (Estimate): February 19, 2016
• Last Update Submitted That Met QC Criteria: February 17, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Neuromuscular Diseases; Peripheral Nervous System Diseases; Chronic Pain; Neuralgia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antipyretics; Gastrointestinal Agents; Analgesics, Opioid; Narcotics; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Dopamine Agents; Narcotic Antagonists; Serotonin and Noradrenaline Reuptake Inhibitors; Cyclooxygenase 2 Inhibitors; Anti-Ulcer Agents; Proton Pump Inhibitors; Gout Suppressants; Duloxetine Hydrochloride; Celecoxib; Acetaminophen; Naloxone; Tramadol; Oxycodone; Esomeprazole; Naproxen
• Other Study ID Numbers: cymbaltaTKR