Pregabalin for Central Sensitization in TKA

Phase 4

Terminated

• Conditions: Osteo Arthritis Knee; Central Nervous System Sensitization
• Interventions: Drug: Pregabalin 75mg

• Registration Number: NCT05460871
• Lead Sponsor: University of Iowa

Brief Summary

The study purpose is to determine if giving pregabalin before and after total knee arthroplasty (TKA) can improve pain and meaningful function after surgery in patients that have central sensitization (CS).

Participants will be identified who are indicated for TKA. Interested patients will complete a standard Knee Injury and Osteoarthritis Outcomes Score (KOOS), asked their pain score (on a scale of 0 to 10), and complete the Central Sensitization Inventory (CSI). If they meet inclusion criteria and agree to participate, they will complete the informed consent before being randomized 1:1 to usual care (control group) or pregabalin (study group). The study group participants will take pregabalin starting 7 days prior to surgery. They will also be scheduled to have a pre-operative physical therapy (PT) appointment which will include tests and measures standard to PT. Tests will include a Timed Up and Go Test (TUG), a Sit to Stand 5 Times Repeat Test (5TSTS) and Patient Specific Functional Scale (SFS) measures.

On the day of surgery participants will be asked about any adverse effects of study medication and determine need to withdraw from study. The post-operative plan will be reviewed, including dose of study medication. For the pregabalin group the doses will be doubled for 7 days, then reduced for 7 days, then off. All participants will be given standard peri-operative pain management for TKA . All participants will complete standard of practice physical therapy.

After surgery (usually within 7 days) a physical therapist will perform standard post-operative evaluation and treatment for all participants. This includes a re-evaluation of the same pre-operative functional tests of TUG, 5TSTS and PSFS outcome measures. The study pharmacist will also call the patient to determine if there are any medication-related adverse effects and how much opioid medication the patient is taking at that time (morphine milligram equivalents- MME/day on average).

At the 6 week post-operative visit all participants will again complete the KOOS survey, report a pain score, complete the CSI survey and determine MME based on patient report of quantity of opioid medication used. A physical therapist will complete the functional assessment of the TUG, 5TSTS and PSFS outcome measures.

Detailed Description

The study purpose is to determine if giving pregabalin before and after total knee arthroplasty (TKA) can improve pain and meaningful function after surgery in patients that have central sensitization (CS). Central sensitization occurs when the brain (central nervous system) becomes hypersensitized and hypervigilant, over-reacting to any painful (and sometimes nonpainful) stimuli. Patients with greater central sensitization have been shown to have significantly more pain after surgery, including TKA. We are proposing to explore whether treatment with a nerve pain medication, pregabalin, can improve post-operative pain and function in these patients. This medication has been shown to improve central sensitization pain in the chronic pain setting but has not been studied for this purpose in the acute surgical pain setting.

Participants will be identified at the visit in which they are indicated for TKA. Patients indicated for a TKA will be approached about participating in the study. Either at that visit or later by phone or e-mail, interested patients will complete a standard Knee Injury and Osteoarthritis Outcomes Score (KOOS), which is part of the standard orthopedic evaluation. They will also be asked their pain score (on a scale of 0 to 10), and complete the Central Sensitization Inventory (CSI). If they meet study inclusion criteria, and they agree to participate, they will complete the informed consent (in person or on-line) and then be randomized 1:1 to usual care (control group) or pregabalin (study group). The study group participants will take pregabalin starting 7 days prior to surgery. The participant will receive usual medication counseling for this medication. They will also be scheduled to have a pre-operative physical therapy (PT) appointment at the time of their pre-op visit, which will include tests and measures standard to PT, but must include a Timed Up and Go Test (TUG), a Sit to Stand 5 Times Repeat Test (5TSTS) and Patient Specific Functional Scale (SFS) measures.

On the day of surgery participants will be asked about any adverse effects of study medication, and determine need to withdraw from study (for any reason). The post-operative plan will also be reviewed, including dose of study medication, for the pregabalin group. For the pregabalin group the doses will be doubled for 7 days, then reduced for 7 days, then off. All participants will be given standard peri-operative pain management for TKA (a nerve block and/or spinal unless contraindicated, anti-inflammatory drugs (NSAID) and acetaminophen (unless contraindicated) as well as oral opioid (usually oxycodone or hydromorphone) to use as needed for severe pain. All participants will complete standard of practice physical therapy on day of surgery or until discharged to home.

After surgery (usually within 7 days) a physical therapist will perform standard post-operative evaluation and treatment for all participants. This includes a re-evaluation of the same pre-operative functional tests of TUG, 5TSTS and PSFS outcome measures. At this time, the pharmacist will also call the patient to determine if there are any medication-related adverse effects and how much opioid medication the patient is taking at that time (morphine milligram equivalents- MME/day on average).

Standard follow-up after TKA is 6 weeks. At this visit all participants will again complete the KOOS survey, report a pain score, complete the CSI survey and determine, based on patient report, of quantity of opioid medication used (MME). A physical therapist will complete the functional assessment of the TUG, 5TSTS and PSFS outcome measures.

Study Timeline

• Study First Submitted: 2022-07-13
• Study First Submitted QC: 2022-07-13
• Study First Posted: 2022-07-15
• Study Start: 2023-02-21
• Primary Completion: 2024-01-25
• Study Completion: 2024-01-25
• Results First Submitted: 2024-02-06
• Status Verified: 2024-03
• Results First Submitted QC: 2024-03-15
• Last Update Submitted: 2024-03-15
• Results First Posted: 2024-03-18
• Last Update Posted: 2024-03-18

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

• Patients undergoing native joint unilateral TKA due to Grade 3-4 primary osteoarthritis
• Patients with score of at least 40 on Central Sensitization Inventory
• Patients who will complete PT within the U of Iowa Health Care system
• Patients who have been nonsmokers for > 2 years
• Patients between the ages of 50 and 85

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Exclusion Criteria

• Patients already taking pregabalin or had an adverse effect with pregabalin in the past
• Patients indicated for joint revision surgery
• Patients taking at least 30 morphine milligram equivalents per day for the past 1 month
• Patients with an estimate GFR < 30 ml/min
• Patients who do not have an understanding of English
• Patients who are pregnant or women of child-bearing years
• Patients who are prisoners
• Patients who score < 40 on the CSI
• Patients who answer Yes to any questions on the Columbia Suicide Severity Rating Scale or express suicidal ideation

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Study (Pregabalin)	Pregabalin 75mg	Participants will receive pregabalin orally 75mg twice daily x 7 days prior to surgery, 150mg twice daily x 7 days after surgery, followed by 75mg twice daily x 7 days. Then Stop.

Primary Outcome Measures

Name	Time	Method
Calculate the Change Using the Knee Osteoarthritis Outcome Survey- Activities of Daily Living Subscale	Approximately 6 weeks	The difference in change on the Knee Osteoarthritis Outcome Survey (KOOS) - Activities of Daily Living subscale will be calculated between the treatment groups. The survey will be administered at baseline and at the subject's 6-weeks post procedure follow-up. The survey is scored on a continuous scale as follows: 1 = none, 2 = mild, 3 = moderate, 4 = severe, 5 = extreme.

Secondary Outcome Measures

Name	Time	Method
Calculate the Change Using the Knee Osteoarthritis Outcome Survey-Sports and Recreational Activities	Approximately 6 weeks	The difference in change on the Knee Osteoarthritis Outcome Survey (KOOS) - Sports and Recreational Activities subscale will be calculated between the treatment groups. The survey will be administered at baseline and at the subject's 6-weeks post procedure follow-up. The survey is scored on a continuous scale as follows: 1 = none, 2 = mild, 3 = moderate, 4 = severe, 5 = extreme.
Calculate the Change Using the Knee Osteoarthritis Outcome Survey-Symptoms	Approximately 6 weeks	The difference in change on the Knee Osteoarthritis Outcome Survey (KOOS) - Symptoms subscale will be calculated between the treatment groups. The survey will be administered at baseline and at the subject's 6-weeks post procedure follow-up. The survey is scored on a continuous scale as follows: 1 = never, 2 = rarely, 3 = sometimes, 4 = often, 5=always.
Calculate the Change Using the Knee Osteoarthritis Outcome Survey-Stiffness	Approximately 6 weeks	The difference in change on the Knee Osteoarthritis Outcome Survey (KOOS) - Stiffness subscale will be calculated between the treatment groups. The survey will be administered at baseline and at the subject's 6-weeks post procedure follow-up. The survey is scored on a continuous scale as follows: 1 = none, 2 = mild, 3 = moderate, 4 = severe, 5 = extreme.
Calculate the Change in Central Sensitization Inventory Score	Approximately 6 weeks	The difference in change on the Central Sensitization Inventory assessment will be calculated between the treatment groups. The survey will be administered at baseline and at the subject's 6-weeks follow-up. The survey is scored on a continuous scale as follows: 1 = never, 2 = rarely, 3 = sometimes, 4 = often, 5 = always.
Calculate the Change of Physical Function Using the Timed Up & Go Assessment	Approximately 6 weeks	The change of physical function using the Timed Up \& Go Assessment (TUG) will be evaluated at four intervals during the study; baseline, during the immediate post-operative time period (day of surgery or post-operative day 1), 7-day follow-up, and at 6-week follow-up. Patients will stand up from a chair, walk approximately 10 feet, turn, walk back and sit back down. This activity will be timed in seconds. The change from baseline until 6-week follow-up will be reported.
Calculate the Change of Physical Function Using the Stand to Sit Assessment	Approximately 6 weeks	The change of physical function using the Stand to Sit Assessment (STS) will be evaluated at four intervals during the study; baseline, during the immediate post-operative time period (day of surgery or post-operative day 1), 7-day follow-up, and at 6-week follow-up. Patients will stand up and sit down from a chair 5 times in a row, as quickly as they can. This activity will be timed in seconds. The change from baseline until 6-week follow-up will be reported.
Calculate the Change of Physical Function Using the Patient-Specific Functional Scale Assessment	Approximately 6 weeks	The change of physical function using the Patient-Specific Functional Scale Assessment (PSFS) will be evaluated at four intervals during the study; baseline, during the immediate post-operative time period (day of surgery or post-operative day 1), 7-day follow-up, and at 6-week follow-up. At baseline, patients will asked to identify activities they are having difficulty/unable to do and would like to gain the mobility back after procedure. The activities will be scored on a continuous rating with The change from baseline until 6-week follow-up will be reported.
Measure the Amount of Pain Reported After Procedure	Approximately 6 weeks	Using a numerical rating scale (0-10), patients will be asked to report their pain level. The scale is from 0 to 10 with 0 being no pain and 10 representing the most intense pain. The pain scores will be collected on 7-day post procedure follow-up and at the 6-week follow up. The change between the timepoints will be reported.
Measure Post-operative Opioid Usage	Approximately 6 weeks	Review with subjects the type and amount of additional pain (opioid) medication required to control their pain. This will be examined approximately 7-day post procedure and at the 6-week post procedure follow-up. The amount of opioid medication taken by the subject will be converted to morphine equivalents for reporting purposes.

Trial Locations

Locations (1)

University of Iowa Hospitals & Clinics; 🇺🇸 Iowa City, Iowa, United States