Reducing Perioperative Oxidative Stress to Prevent Postoperative Chronic Pain Following Total Knee Arthroplasty

NCT06083480 | Recruiting Phase 4 DMC FDA Drug

• 2 other identifiers: 2316681R01AG085287-01
• Study Type: interventional
• Target: 148
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective randomized controlled trial that will assess preoperative, perioperative, and long-term oxidative stress (OS); pain; and functional outcomes over a 12 month period and test the hypothesis that a potent antioxidant intervention (glycine + N-acetyl-cysteine(GlyNAC)) reduces oxidative stress and chronic post surgical pain (CPSP) in patients undergoing total knee arthroplasty (TKA).

Conditions

Osteoarthritis, Knee; Total Knee Arthroplasty; Chronic Postsurgical Pain

Outcome Measures

Primary Outcomes (1)

• Numeric Rating Scale (NRS) Rating of Worst Pain in the past 24 hours

  Mean within participant changes in NRS intensity ratings of worst pain in past 24 hours of measurement at 6 months post TKA. The score is a rating of current acute pain using a 0-100 numeric rating scale (NRS) (0 = "no pain" and 100 = "worst possible pain").

  Baseline to 6 months post TKA (approximately 7 months)

Secondary Outcomes (10)

• Numeric Rating Scale (NRS) Rating of Worst Pain in the past 24 hours

  Baseline to 6 weeks and 12 months post TKA (13 months)

• Numeric Rating Scale of Average Pain in the past 24 hours

  Baseline to 6 weeks, 6 months and 12 months post TKA (13 months)

• Numeric Rating Scale of Least Pain in the past 24 hours

  Baseline to 6 weeks, 6 months and 12 months post TKA (13 months)

• Mean change in McGill Pain Questionnaire-2 (MPQ-2) ratings of knee pain for average pain over past week of measurement.

  Baseline to 6 weeks, 6 months and 12 months post TKA (13 months)

• Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS-JR)

  Baseline to 6 weeks, 6 months and 12 months post TKA (13 months)

Study Arms (2)

GlyNAC (combination of glycine and n-acetylcysteine)

EXPERIMENTAL

GlyNAC 200 mg/kg/day (100mg glycine and 100mg N-acetyl-cysteine) will be administered orally in two divided doses each day for four weeks prior to TKA and six weeks postoperatively. The preparation will be a commercially available product of 1:1 ratio of glycine and N-acetyl-cysteine.

Drug: GlyNAC (combination of glycine and n-acetylcysteine)

Placebo (alanine)

PLACEBO COMPARATOR

Placebo (alanine) 200 mg/kg/day will be administered orally in two divided doses each day for four weeks prior to TKA and six weeks postoperatively.

Drug: Placebo

Interventions

GlyNAC (combination of glycine and n-acetylcysteine) DRUG

GlyNAC 200 mg/kg/day (100mg glycine and 100mg N-acetyl-cysteine) will be administered orally in two divided doses each day for four weeks prior to TKA and six weeks postoperatively. The preparation will be a commercially available product of 1:1 ratio of glycine and N-acetyl-cysteine.

Also known as: GlyNAC

GlyNAC (combination of glycine and n-acetylcysteine)

Placebo DRUG

Placebo (alanine) 200 mg/kg/day will be administered orally in two divided doses each day for four weeks prior to TKA and six weeks postoperatively.

Placebo (alanine)

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 50 or older
• Intact cognitive status and ability to provide informed consent (based on cognitive screening with the Mini Mental State Examination)
• Ability to read and write in English sufficiently to understand and complete study questionnaires
• Undergoing unilateral primary TKA
• Medical diagnosis of osteoarthritis
• Past 24 hour worst numeric rating scale (NRS) pain of at least 4/10.

You may not qualify if:

• Diagnosis of pre-existing neuropathy
• Untreated hypo/hyperthyroidism
• Untreated heart disease
• Alanine transaminase/aspartate transaminase \>2x upper-limit of normal range
• serum creatinine \>1.5 mg/dl
• Pregnancy
• Complex Regional Pain Syndrome (CRPS) diagnosis prior to undergoing TKA
• Presence of lower extremity vascular disease, inflammatory or autoimmune disorders, or malignancy
• Presence of current clinically significant chronic pain conditions outside of the lower extremity ( daily pain for \>3 months and greater ≥3/10 in intensity or the focus of medical care)
• Presence of other medical conditions that in the opinion of the orthopedic surgeon co-investigators would make a patient's study participation unsafe

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37212, United States

RECRUITING

MeSH Terms

Conditions

Osteoarthritis, Knee; Pain, Postoperative

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Stephen Bruehl, Ph.D.

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

• Frederic T Billings, IV, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stephen Bruehl, Ph.D.

CONTACT

(615) 936-1821; stephen.bruehl@vumc.org

Gail Mayo, RN

CONTACT

615-936-1705; gail.mayo@vumc.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Anethesiology

Model Details: Prospective, randomized, controlled, mixed between/within-subject longitudinal trial

Study Record Dates

• First Submitted: October 5, 2023
• First Posted: October 16, 2023
• Study Start: December 6, 2024
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): March 1, 2029
• Last Updated: December 11, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: The data will be made available in OSF upon publication of the project findings.
• Access Criteria: OSF provides a unique URL for all datasets which will be provided for those interested. OSF also includes an interface with a search engine for identify datasets by topic/keyword.

Locations

US (1)