Vitamin C for Postoperative Knee Pain

(PROVISION Trial)

Recruiting at 2 trial locations

Overseen By Nour Ayach

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mount Sinai Hospital, Canada

Disqualifiers: Infection, Fracture, Lupus, others

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

Compensation: Varies

Number of Visits: 4

Duration: 8 weeks

300 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether taking vitamin C before knee replacement surgery can reduce long-term pain after the operation. Participants will receive either vitamin C or a placebo (a harmless pill with no active ingredients) to determine which is more effective. The trial seeks individuals scheduled for knee replacement surgery due to severe arthritis, excluding those with certain health issues like kidney problems or a history of specific autoimmune diseases. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that vitamin C is usually safe to use around the time of knee surgery. Studies have found that patients who took vitamin C after knee replacement surgery experienced less swelling, as indicated by lower levels of inflammation markers like CRP and ESR. Other research found that people who used vitamin C reported feeling less pain immediately after surgery compared to those who didn't take it, suggesting that vitamin C might help manage pain effectively.

Additionally, vitamin C has been noted to reduce blood loss during surgery, aiding recovery. These studies suggest that vitamin C is safe to use during surgery, but consulting a doctor before joining a trial is always advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for knee pain?

Unlike the standard treatments for postoperative knee pain, which often include NSAIDs or opioids, Vitamin C offers a potentially safer and non-addictive option. Researchers are excited about Vitamin C because it acts as an antioxidant, which may reduce inflammation and pain without the side effects associated with traditional pain medications. This approach could lead to faster recovery and improved comfort for patients after knee surgery.

What evidence suggests that Vitamin C might be an effective treatment for postoperative knee pain?

Research shows that vitamin C might help reduce pain after knee surgery. In this trial, participants in the intervention arm will receive preoperative Vitamin C capsules. One study found that taking vitamin C after total knee replacement surgery lowered signs of inflammation, such as CRP and ESR. Another study showed that patients who took vitamin C reported less pain on the first day after surgery compared to those who didn't. Additionally, research has shown that vitamin C reduces blood loss after surgery, aiding recovery. Overall, these findings suggest vitamin C could effectively ease pain and inflammation for knee surgery patients. ^{1 2 3 4 5}

Who Is on the Research Team?

Jesse I Wolfstadt, MD

Principal Investigator

Mount Sinai Hospital; Department of Surgery

James Khan, MD

Principal Investigator

University Health Network; Department of Anesthesia and Pain Medicine

Raman Mundi, MD

Principal Investigator

Holland Orthopedic and Arthritic Centre

Harman Chaudhry, MD

Principal Investigator

Holland Orthopedic and Arthritic Centre

Are You a Good Fit for This Trial?

This trial is for adults over 18 who are having knee replacement surgery because of severe arthritis. It's not for those with knee replacements due to infection, fractures, certain autoimmune conditions, or if they're pregnant. Participants must be able to follow up and fill out questionnaires in the study language.

Inclusion Criteria

I am older than 18 years.

I am having knee replacement surgery due to severe arthritis.

Exclusion Criteria

Pregnant or planning to become pregnant during the study

I need a knee replacement due to infection, fracture, or specific arthritis types.

Unlikely to comply with follow-up (e.g., no fixed address, plans to move out of town)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 2000 mg of vitamin C orally within 4 hours of surgery, followed by 500 mg twice daily from post-operative day 1 to day 56

8 weeks

Visits on post-operative days 1-3, weeks 2, 4, 6, and 8

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments of pain, opioid consumption, and quality of life

12 months

Visits at 3 months and 12 months post-operatively

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Vitamin C

Trial Overview The study tests if Vitamin C can reduce long-term pain after knee replacement surgery compared to a placebo. It's a Phase II trial where participants are randomly assigned to either Vitamin C or placebo in equal numbers without knowing which one they receive.

How Is the Trial Designed?

Group I: Intervention Experimental Treatment 1 Intervention

Preoperative Vitamin C capsules

Group II: Placebo Placebo Group 1 Intervention

Preoperative placebo capsules

Who Is Running the Clinical Trial?

Mount Sinai Hospital, Canada

Lead Sponsor

Trials

210

Recruited

70,700+

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

The Arthritis Society, Canada

Collaborator

Trials

27

Recruited

9,700+

Published Research Related to This Trial

Vitamin C significantly reduces acute postoperative pain and morphine consumption, as shown in a meta-analysis of seven randomized controlled trials involving various patient groups.

Intravenous vitamin C was particularly effective, leading to lower pain scores and reduced opioid needs both 1-2 hours and 24 hours after surgery, while oral vitamin C did not show the same benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Perioperative Vitamin C on Postoperative Analgesic Consumption: A Meta-Analysis of Randomized Controlled Trials. Hung, KC., Lin, YT., Chen, KH., et al.[2021]

A single prophylactic dose of 2 g of vitamin C significantly reduced morphine consumption in the first 24 hours after laparoscopic cholecystectomy, with patients taking an average of 16.2 mg compared to 22.8 mg in the placebo group.

There were no differences in pain scores or side effects between the vitamin C and placebo groups, indicating that vitamin C is a safe option for reducing opioid use without compromising patient satisfaction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of vitamin C on morphine use after laparoscopic cholecystectomy: a randomized controlled trial. Kanazi, GE., El-Khatib, MF., Yazbeck-Karam, VG., et al.[2013]

A systematic review of 23 studies involving 642 patients found that plasma vitamin C levels significantly decreased after surgery, with a 39% depletion in the first week and a 21% depletion 2-3 months post-surgery.

The observed reductions in vitamin C levels varied by surgery type, highlighting the need for further research to understand the clinical implications of these changes and to explore long-term effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of surgery on plasma/serum vitamin C concentrations: a systematic review and meta-analysis. Travica, N., Ried, K., Hudson, I., et al.[2022]

In a study of 95 patients undergoing total knee arthroplasty, perioperative vitamin C supplementation (1000 mg daily) did not significantly improve range of motion after one year, but it did show a trend towards reducing the incidence of arthrofibrosis (AF) compared to placebo (10.4% vs. 23.4%).

Vitamin C levels dropped significantly in the placebo group post-surgery, while the VC group maintained their levels, suggesting that vitamin C supplementation is a safe and cost-effective strategy to potentially lower the risk of AF after knee surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin C demand is increased after total knee arthroplasty: a double-blind placebo-controlled-randomized study. Behrend, H., Lengnick, H., Zdravkovic, V., et al.[2020]

Vitamin C is associated with improved bone health and tendon healing, and it may help reduce postoperative pain and prevent complex regional pain syndrome after orthopedic surgeries, based on current research.

There is a need for high-quality human trials to better understand the optimal dosage and administration of vitamin C to enhance outcomes in orthopedic procedures, particularly in joint replacement and ACL reconstruction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin C in orthopedic practices: Current concepts, novel ideas, and future perspectives. Oakes, B., Bolia, IK., Weber, AE., et al.[2021]

In a randomized controlled trial involving patients who underwent surgery for isolated foot and ankle trauma, vitamin C supplementation (500mg twice daily) significantly reduced post-operative pain and analgesia requirements compared to a placebo.

Patients receiving vitamin C showed improved pain scores (VAS) at two and six weeks post-surgery and achieved better functional outcomes, indicating that vitamin C may enhance recovery after surgical procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of anti-oxidant (vitamin-C) in post-operative pain relief in foot and ankle trauma surgery: A prospective randomized trial. Jain, SK., Dar, MY., Kumar, S., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12486973/

The impact of vitamin C supplementation on ... Conclusion. Perioperative VC supplementation for THA/TKA may alleviate pain and reduce inflammatory responses within 24 h. Large-scale, high- ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10532858/

Anti-Inflammatory Effect of Vitamin C during the ... Patients who received 15 g of vitamin C after total knee replacement surgery had decreased inflammatory markers, specifically CRP and ESR.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06123715

Perioperative Vitamin C to Reduce Persistent Pain After ... Drug: Patients in the intervention group will receive 2g Vitamin C orally within 4 hours of the start of the surgery followed by 500 mg of Vitamin C to be taken ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2352344125000056

Ascorbic Acid Reduces the Blood Boss After Total Knee ... Our findings demonstrated that perioperative use of ascorbic acid can reduce blood loss by nearly 36% on the first postoperative day.

5. journals.lww.com journals.lww.com/jbjsjournal/fulltext/2025/05210/efficacy_of_vitamin_c_as_glucocorticoid_substitute.11.aspx

Efficacy of Vitamin C as Glucocorticoid Substitute for... : JBJS Compared with patients in the control group, those who received vitamin C or dexamethasone reported a significantly lower VAS pain score on postoperative day 1, ...