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

Trial Summary

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.

What data supports the effectiveness of the drug Vitamin C for reducing postoperative knee pain?

Research shows that Vitamin C can lower pain scores and reduce the need for painkillers like morphine after surgery, suggesting it may help with knee pain after surgery. However, more studies are needed to confirm the best dose and method of taking it. ^{1 2 3 4 5}

Is Vitamin C safe for use in humans, particularly for postoperative knee pain?

Vitamin C is generally considered safe for use in humans, including in the context of postoperative care. It is an important antioxidant and has been associated with improved bone health and reduced postoperative pain in various studies. However, more high-quality human trials are needed to confirm its safety and optimal dosage in specific surgical settings. ^{1 2 3 4 6}

How does the drug Vitamin C differ from other treatments for postoperative knee pain?

Vitamin C is unique because it is an antioxidant that can reduce pain and the need for opioids (strong painkillers) after surgery, especially when given intravenously (through a vein). This makes it different from standard pain treatments that often rely on medications like opioids, which can have more side effects. ^{1 2 3 4 6}

What is the purpose of this trial?

Phase II Multicentre, pilot, parallel-group, blinded, 1:1 randomized controlled trial to determine the feasibility of conducting a larger definitive trail of using vitamin C to reduce persistent pain in patients undergoing total knee arthroplasty surgery.

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

The Effect of Perioperative Vitamin C on Postoperative Analgesic Consumption: A Meta-Analysis of Randomized Controlled Trials. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

Vitamin C demand is increased after total knee arthroplasty: a double-blind placebo-controlled-randomized study. [2020]

3. France 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. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Vitamin C in orthopedic practices: Current concepts, novel ideas, and future perspectives. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Effect of vitamin C on morphine use after laparoscopic cholecystectomy: a randomized controlled trial. [2013]

6. England pubmed.ncbi.nlm.nih.gov

The effects of surgery on plasma/serum vitamin C concentrations: a systematic review and meta-analysis. [2022]