NAC-REPAIR for Post-surgical Pain

NCT07227649 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: STUDY00007009
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot asks whether peri-operative N-acetylcysteine (NAC) improves recovery after common outpatient hand/foot-ankle surgery-specifically, does NAC reduce pain and opioid use and enhance function by modulating redox-inflammatory pathways? Primary objectives are to establish feasibility (accrual, adherence, follow-up), estimate NAC vs placebo effects on pain, function, and opioid consumption, and characterize inflammatory signatures that may predict response. Methods: a single-site, double-blind, 1:1 randomized trial (N≈80) comparing NAC 1,200 mg twice daily for 14 days (starting pre-op) vs matching placebo; daily e-diaries for POD0-14; standardized outcomes (PROMIS Pain Interference; QuickDASH or FAAM; PGIC; opioid MME); and small blood draws pre-surgery and at two follow-up visits for cytokine profiling.

Conditions

Carpal Tunnel Surgery; Trigger Finger Disorder; De Quervain Syndrome; Guyon's Canal; Dupuytren Contracture; Morton Neuroma; Tarsal Tunnel Syndrome; Plantar Fasciopathy; Peroneal Nerve Entrapment

Outcome Measures

Primary Outcomes (1)

• PROMIS pain interference

  Patient-Reported Outcomes Measurement Information System - Pain Interference T-score metric: mean = 50, SD = 10 Higher scores = worse outcome (greater pain interference with daily activities, social, cognitive, emotional, and physical functioning)

  baseline; post-op (2-4 weeks); post-op (12 weeks);

Secondary Outcomes (2)

• PROMIS Physical Function

  Baseline; post-op (2-4 weeks); post-op (12 weeks)

• Numeric Pain Rating Scale

  Baseline; post-op (2-4 weeks); post-op (12 weeks)

Study Arms (2)

N-Acetylcysteine (NAC)

EXPERIMENTAL

Intervention: Oral N-acetylcysteine capsules, 600 mg twice daily. Timing/Duration: Begin the evening before surgery (≤24 h pre-op) and continue through Post-op Day 14 (total 15 days; bottle overfilled to cover missed doses). Administration: Self-administered at home; counseling at baseline dispense; pill diary + pill counts. Concomitant care: All peri-operative care per standard of care (SoC), including multimodal analgesia; no high-dose antioxidant supplements; nitrates excluded. Objective: Test whether peri-operative NAC improves early pain, function, and recovery via redox-immune modulation.

Drug: NAC

Placebo

PLACEBO COMPARATOR

Intervention: Matched inert capsules (e.g., microcrystalline cellulose), identical in size/appearance/labeling to NAC. Timing/Duration: 600 mg-equivalent capsule count, twice daily, evening before surgery through Post-op Day 14. Administration: Same counseling, diary, and adherence checks as NAC arm. Concomitant care: Identical SoC allowances/restrictions as NAC arm.

Drug: NAC 0mg/day (Placebo)

Interventions

NAC DRUG

Intervention: Oral N-acetylcysteine capsules, 600 mg twice daily. Timing/Duration: Begin the evening before surgery (≤24 h pre-op) and continue through Post-op Day 14 (total 15 days; bottle overfilled to cover missed doses). Administration: Self-administered at home; counseling at baseline dispense; pill diary + pill counts. Concomitant care: All peri-operative care per standard of care (SoC), including multimodal analgesia; no high-dose antioxidant supplements; nitrates excluded. Objective: Test whether peri-operative NAC improves early pain, function, and recovery via redox-immune modulation.

N-Acetylcysteine (NAC)

NAC 0mg/day (Placebo) DRUG

Intervention: Matched inert capsules (e.g., microcrystalline cellulose), identical in size/appearance/labeling to NAC. Timing/Duration: 600 mg-equivalent capsule count, twice daily, evening before surgery through Post-op Day 14. Administration: Same counseling, diary, and adherence checks as NAC arm. Concomitant care: Identical SoC allowances/restrictions as NAC arm. Randomization/Blinding: 1:1, stratified by surgery type (upper- vs lower-extremity); double-blind (participants, investigators, assessors). Primary comparisons: Early postoperative pain and function (e.g., PROMIS-PI/PF, QuickDASH or LEFS), opioid consumption; safety/tolerability.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Elective outpatient hand/upper-extremity or foot/ankle surgery (single site; same-day discharge)
• Baseline visit feasible ≤14 days pre-op
• Can complete surveys/blood draw
• Provides informed consent
• Willing to follow dosing schedule and avoid restricted supplements/meds

You may not qualify if:

• Allergy to NAC/capsule components □ NAC or high-dose antioxidants in past 14 days (unwilling to stop)
• Chronic daily opioids ≥3 months or OUD/maintenance therapy □ Pregnant/breastfeeding or no contraception as applicable
• Daily nitrates (nitroglycerin/isosorbide) □ Planned \>24h admission, multistage/trauma case □ Other interventional study within 30 days
• Unable to swallow capsules / malabsorption surgery affecting oral meds

Sponsors & Collaborators

• University of Arizona: lead
• Banner University Medical Center: collaborator

Study Sites (1)

Banner Health

Tucson, Arizona, 85721, United States

Location

MeSH Terms

Conditions

Trigger Finger Disorder; Dupuytren Contracture; Morton Neuroma; Tarsal Tunnel Syndrome; Peroneal Neuropathies

Condition Hierarchy (Ancestors)

Tendon Entrapment; Tendinopathy; Muscular Diseases; Musculoskeletal Diseases; Fibroma; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Contracture; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metatarsalgia; Foot Diseases; Joint Diseases; Neuralgia; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Tibial Neuropathy; Mononeuropathies; Nerve Compression Syndromes

Central Study Contacts

Valerio Tonelli Enrico, PT, PhD, MSCE

CONTACT

17068097067; vte@arizona.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2025
• First Posted: November 13, 2025
• Study Start: January 15, 2026
• Primary Completion (Estimated): January 15, 2027
• Study Completion (Estimated): July 15, 2027
• Last Updated: November 14, 2025

Record last verified: 2025-11

Locations

US (1)