Reducing perioperative oxidative stress to prevent postoperative chronic pain following total knee arthroplasty

Ended Project Grant Awarded Last action

Award ID
R01AG085287
Recipient
Awarding agency
Obligated
$2,698,358

Award facts

Assistance listing
93.866 Aging Research
Completion date
Place of performance
Nashville, TN 37203, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Approximately 1 million total knee arthroplasty (TKA) procedures are carried out in the U.S. Annually to address pathology underlying knee joint pain and functional limitations resulting from osteoarthritis. Tkas are conducted primarily in older adults, and while effective for pain reduction in many, 15% or more of TKA patients report unsatisfactory long-term pain outcomes despite a technically successful surgery. Post-TKA pain at up to 4-year follow-up has been reported to be worse than the preoperative pain in 7% of TKA patients. While mechanisms contributing to long-term pain post-TKA are not well-understood, our prior longitudinal project (R01AG048915) found evidence that oxidative stress (OS) may be one contributor to post-TKA chronic pain. Elevated intraoperative pre-incision levels of F2-isoprostanes and isofurans (the most sensitive in vivo OS biomarkers) and increased expression of these biomarkers during tourniquet application in standard TKA procedures predicted greater post-TKA pain intensity (past 24 hour and past week) at 6-months post-TKA. The proposed project builds on this prior work and will answer a critical clinical question: does reducing OS in the preoperative and perioperative period improve long-term post-TKA pain outcomes? We propose a prospective randomized placebo-controlled trial that will examine preoperative, perioperative, and long-term OS; pain; and functional outcomes and test for the first time the hypothesis that a potent antioxidant intervention (glycine plus n-acetylcysteine [glynac]) reduces OS and chronic postsurgical pain in patients undergoing TKA. Glynac has been shown to dramatically decrease F2-isoprostanes in initial trials, supporting its potential utility as an antioxidant intervention for improving post-TKA pain outcomes. Given the large number of older adults experiencing adverse post-TKA chronic pain outcomes each year (˜150,000 annually), the proposed project could potentially have practice-changing clinical implications. We will enroll older adult osteoarthritis patients undergoing primary unilateral TKA and randomize them to receive glynac (n=74) or placebo (alanine; n = 74) beginning 4 weeks prior to TKA with continuation until 6 weeks post-TKA. Baseline pain and psychosocial phenotyping will be carried out and OS will be assessed in the patient's home at 4 weeks pre-TKA (T0) and again after 4 weeks of the intervention [3 days prior to TKA] (T1); perioperatively at pre-incision [T2], 45 minutes after tourniquet application [T3], and 15 minutes post-tourniquet removal [T4]; and at post-TKA follow- UPS. Pain, function, and opioid use outcomes will be assessed at 6-week, 6-month, and 12-month follow-up. We will test the hypothesis that glynac reduces OS and pain intensity, improves function, and reduces opioid analgesic use at 6-week and 6-month (primary) follow-up compared to placebo. We will also test whether glynac-related reductions in pain intensity at 6-month follow-up are maintained at 12-month follow-up, and whether pre-glynac baseline OS levels moderate efficacy of glynac for improving long-term pain outcomes.

Transactions

Action Obligated Date
Amendment $0
Amendment $0
Amendment $0
Amendment $949,178
Amendment $0
Amendment $0
Amendment $874,590
Original award $874,590

Subawards

Subrecipient Amount Awarded
Baylor College Of Medicine Reducing Perioperative Oxidative Stress to Prevent Postoperative Chronic Pain Following Total Knee Arthroplasty $91,352
Baylor College Of Medicine $93,216
Baylor College Of Medicine $111,360

Quick answers

Who received award R01AG085287?

R01AG085287 was awarded to Vanderbilt University Medical Center by National Institute on Aging (National Institutes of Health) on September 30, 2023.

How much is award R01AG085287 worth?

$2,698,358 has been obligated on R01AG085287.

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