NAC for Surgery Recovery

Overseen By Valerio Tonelli Enrico, PT, PhD, MSCE

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Arizona

Must not be taking: Chronic opioids, Nitrates

Disqualifiers: Pregnancy, Malabsorption surgery, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether N-acetylcysteine (NAC), a supplement, can aid recovery from common outpatient hand or foot surgeries. The goal is to determine if NAC can reduce pain, lower opioid use, and enhance post-surgery function by influencing inflammation-related body processes. Participants will be randomly assigned to take NAC or a placebo (a pill with no active ingredient) for 14 days, starting the day before surgery. Individuals undergoing elective outpatient hand or foot/ankle surgery who can adhere to the study's dosing schedule are suitable candidates. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial requires participants to avoid certain supplements and medications, but it doesn't specify which ones. If you're taking high-dose antioxidants or daily nitrates, you may need to stop. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that N-acetylcysteine is likely to be safe for humans?

Research has shown that N-acetylcysteine (NAC) is generally safe for most people. Studies have found that taking NAC orally is usually safe, though some individuals might experience mild side effects such as an upset stomach, itching, or asthma-like symptoms. The FDA has approved NAC as a prescription drug, which enhances confidence in its safety. In some cases, NAC has helped individuals recover after surgery by reducing pain and the need for painkillers. Overall, NAC appears to be a safe choice for most adults, with only minor side effects for some. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for surgery recovery, which typically involves pain management with medications like opioids or NSAIDs, N-acetylcysteine (NAC) offers a unique approach by targeting oxidative stress and immune response. NAC is an antioxidant that may help improve recovery by modulating redox balance and immune function, potentially reducing pain and enhancing postoperative recovery. Researchers are excited about NAC because it might offer a safer alternative to conventional pain medications, with fewer side effects and a novel mechanism that directly supports the body's healing process.

What evidence suggests that N-acetylcysteine might be an effective treatment for surgery recovery?

Research has shown that N-acetylcysteine (NAC), which participants in this trial may receive, might help reduce pain after surgery. One small study found that taking NAC before surgery lowered pain levels and reduced the need for pain medication. Although results vary across different types of surgery, early evidence is promising for pain management. NAC affects certain body processes that decrease inflammation and pain after surgery. While more research is needed, NAC's potential to aid recovery by reducing pain and inflammation makes it an interesting option for surgery patients. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals undergoing common outpatient hand/foot-ankle surgeries, such as those for carpal tunnel syndrome or plantar fasciitis. Participants should be interested in testing if the antioxidant N-acetylcysteine (NAC) can help with pain and recovery post-surgery.

Inclusion Criteria

Provides informed consent

I am willing to stick to the treatment plan and avoid certain supplements or medications.

Can complete surveys/blood draw

Exclusion Criteria

I have taken high-dose antioxidants or NAC in the last 14 days and am unwilling to stop.

I have been using opioids daily for more than 3 months or am on maintenance therapy for opioid use disorder.

Pregnant/breastfeeding or no contraception as applicable

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive N-acetylcysteine (NAC) or placebo starting the evening before surgery and continuing for 14 days post-surgery

2 weeks

Daily e-diaries for POD0-14; small blood draws pre-surgery

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits for cytokine profiling

12 weeks

2 follow-up visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• N-acetylcysteine

Trial Overview The study tests whether taking NAC (1,200 mg twice daily) versus a placebo for two weeks around surgery time improves pain management, reduces opioid use, and enhances function. It's a double-blind trial where neither doctors nor patients know who gets the real medicine.

How Is the Trial Designed?

Group I: N-Acetylcysteine (NAC) Experimental Treatment 1 Intervention

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.

Group II: Placebo Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

University of Arizona

Lead Sponsor

Trials

545

Recruited

161,000+

Banner University Medical Center

Collaborator

Trials

10

Recruited

3,200+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11486111/

Perioperative N-acetylcysteine: evidence and indications Overall analysis found that NAC significantly improved incidence of primary graft nonfunction, postoperative liver function (as measured by peak liver enzyme ...

2. academic.oup.com academic.oup.com/bjs/article/110/Supplement_8/znad348.162/7428783

HPB P23 Investigating the effect of N-acetylcysteine on ... This meta-analysis of RCTs has shown that the administration of NAC in patients undergoing liver resection did not alter important biochemical parameters.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S105307701000193X

N-acetylcysteine in Cardiac Surgery: Do the Benefits ... Current evidence shows that the perioperative use of NAC has no proven benefit or risk on clinically important outcomes in patients undergoing cardiac surgery.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03354572

Pilot Study: Postoperative Pain Reduction by Pre Emptive ... Based on these promising results, we hypothesize that pre emptive intravenous NAC can reduce postoperative pain and thereby cause less necessity for escape ...

5. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/201251

Perioperative N-acetylcysteine to Prevent Renal ... Conclusions N-acetylcysteine did not prevent postoperative renal dysfunction, interventions, complications, or mortality in high-risk patients ...

6. webmd.com webmd.com/vitamins/ai/ingredientmono-1018/n-acetyl-cysteine-nac

N-Acetyl Cysteine (Nac) – Uses, Side Effects, and More When taken by mouth: N-acetyl cysteine is likely safe for most adults. N-acetyl cysteine is an FDA-approved prescription drug. It can cause side effects such as ...

7. tandfonline.com tandfonline.com/doi/abs/10.1080/17581869.2024.2388504

Perioperative N-acetylcysteine: evidence and indications While NAC is generally well tolerated and considered safe, stomach upset can occur as can itching or asthma like reactions in certain patients.

8. academic.oup.com academic.oup.com/ejcts/article/35/3/521/402843

Use of N-acetylcysteine to reduce post-cardiothoracic surgery ... Upon meta-analysis of 13 trials (n = 1338 subjects), the use of NAC appeared to statistically significantly lower the odds of developing post-CTS AF by 36% (95% ...