Vitamin C for Acute Pain

(Vicamed Trial)

Overseen By Martin Marquis, MSc

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Centre Integre Universitaire de Sante et Services Sociaux du Nord de l'ile de Montreal

Must be taking: NSAIDs

Must not be taking: Opioids, Vitamin C, Cyclosporine, Warfarin

Disqualifiers: Active cancer, Chronic pain, Allergy, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether vitamin C can reduce pain for individuals with sudden muscle or bone pain, such as a sprain or fracture, after an emergency room visit. Participants will take either vitamin C or a placebo, along with regular acetaminophen, to determine if it reduces pain over a week and prevents long-term pain after three months. This trial may suit someone who has experienced severe muscle or bone pain within the last 48 hours, has been advised to take NSAIDs (but not opioids) for pain, and can track pain levels daily. As an unphased trial, this study provides a unique opportunity to contribute to understanding pain management with vitamin C.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently using vitamin C supplements or are treated with cyclosporine or warfarin. You will be taking acetaminophen regularly and can use naproxen if needed for pain.

Is there any evidence suggesting that vitamin C is safe for managing acute musculoskeletal pain?

Research has shown that vitamin C is a safe option for pain relief with minimal side effects. One study found that even at high doses, vitamin C remained safe and well-tolerated. Another study highlighted its ability to reduce pain without causing significant issues. Overall, taking vitamin C in recommended amounts is generally safe. However, excessive intake can occasionally lead to mild issues like an upset stomach, though this is rare and typically occurs only with very high doses. For those considering joining a trial, vitamin C appears to be a safe and well-tolerated choice. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using vitamin C for acute pain because it offers a potential new approach to managing pain with a natural ingredient. While most treatments for acute pain, like acetaminophen and NSAIDs such as naproxen, work by reducing inflammation or blocking pain signals, vitamin C might help by enhancing the body's natural antioxidant defenses. This could mean fewer side effects and a different way to tackle pain, which might benefit those who can't tolerate standard pain medications. Plus, vitamin C is already widely recognized for its safety and benefits, adding to researchers' enthusiasm about exploring its new potential in pain management.

What evidence suggests that vitamin C might be an effective treatment for acute pain?

Research has shown that vitamin C might help reduce pain, especially soon after surgery. In this trial, one group of participants will receive acetaminophen and vitamin C, while another group will receive acetaminophen and a placebo. Studies have found that high doses of vitamin C can lessen pain and decrease the need for other pain medications shortly after surgery. Vitamin C is usually safe and has few side effects. It might also help manage both short-term and long-term pain in some patients, making it a promising option for those who can't use standard anti-inflammatory drugs. ^{2 6 7 8 9}

Who Is on the Research Team?

Raoul Daoust, MD MSc

Principal Investigator

Université de Montréal

Are You a Good Fit for This Trial?

This trial is for adults over 18 who visited the emergency department with acute musculoskeletal pain, like a fracture or sprain, that's lasted less than 48 hours. They should have a pain level of at least 4 out of 10 and be prescribed NSAIDs without opioids. It's not suitable for those who can't safely take vitamin C or acetaminophen.

Inclusion Criteria

Numerical rating scale (NRS) pain intensity at triage of ≥ 4 on a 0-10 scale

I was treated in the emergency department for sudden muscle or joint pain within 2 days of it starting.

I speak French or English.

Exclusion Criteria

I am currently taking vitamin C supplements.

Received an opioid prescription at ED discharge

Allergy to milk (lactose in the placebo), vitamin C, acetaminophen or NSAIDs

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either 900 mg of vitamin C or a placebo, twice a day for seven days, along with acetaminophen. Naproxen is used as a rescue medication.

1 week

Daily self-reporting via electronic or paper diary

Follow-up

Participants are monitored for safety, pain relief, and adverse events. Chronic pain development is assessed at three months.

3 months

1 visit (in-person) at 90 days

What Are the Treatments Tested in This Trial?

Interventions

• Vitamin C

Trial Overview The study tests if vitamin C can help reduce pain after an ED visit for acute musculoskeletal issues. Participants will either get vitamin C or a placebo twice daily for seven days, along with regular doses of acetaminophen. Naproxen is provided as backup if needed.

How Is the Trial Designed?

Group I: Acetaminophen and Vitamin C with Naproxen rescue Experimental Treatment 1 Intervention

900 mg vitamin C taken orally twice a day Extended-release acetaminophen 650 mg two pills every eight hours regularly Naproxen 500 mg as a rescue medication

Group II: Acetaminophen and Placebo with Naproxen rescue Placebo Group 1 Intervention

Placebo taken orally twice a day Extended-release acetaminophen 650 mg two pills every eight hours regularly Naproxen 500 mg as a rescue medication

Vitamin C is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Vitamin C for:

• Scurvy
• Dietary supplement

Approved in European Union as Vitamin C for:

• Scurvy
• Dietary supplement

Approved in Canada as Vitamin C for:

• Scurvy
• Dietary supplement

Who Is Running the Clinical Trial?

Centre Integre Universitaire de Sante et Services Sociaux du Nord de l'ile de Montreal

Lead Sponsor

Trials

17

Recruited

4,600+

Hopital du Sacre-Coeur de Montreal

Lead Sponsor

Trials

52

Recruited

12,100+

Hopital de l'Enfant-Jesus

Collaborator

Trials

17

Recruited

5,800+

The Ottawa Hospital

Collaborator

Trials

97

Recruited

64,000+

Published Research Related to This Trial

Vitamin C administration has been shown to reduce pain in various conditions, including chronic regional pain syndrome and cancer-related pain, suggesting its potential as an effective adjunctive therapy for pain relief.

A proposed mechanism for vitamin C's analgesic properties is its role as a cofactor in the biosynthesis of amidated opioid peptides, which may help decrease the need for opioid analgesics in patients receiving high doses of vitamin C.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of vitamin C in the treatment of pain: new insights. Carr, AC., McCall, C.[2022]

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 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 systematic review of 80 randomized controlled trials (RCTs) on noninvasive analgesic treatments revealed that adverse event (AE) reporting was often incomplete, with over 40% of trials not reporting any serious adverse events.

The review highlighted that trials involving participants with pain conditions and those sponsored by industry provided better AE data, indicating a need for improved consistency and thoroughness in AE reporting across all analgesic RCTs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse event assessment, analysis, and reporting in recent published analgesic clinical trials: ACTTION systematic review and recommendations. Smith, SM., Wang, AT., Katz, NP., et al.[2023]

In a study of 8677 patients, the use of analgesics like paracetamol, aspirin, and ibuprofen showed that the main risk factors for serious adverse events (SAE) included the type of pain being treated and the number of other medications taken, with higher risks associated with more medications.

Patients taking aspirin had a higher risk of SAE compared to those taking paracetamol, while ibuprofen was associated with fewer gastrointestinal adverse events, highlighting the importance of medication choice and patient history in managing pain safely.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk factors for adverse events in analgesic drug users: results from the PAIN study. Moore, N., Charlesworth, A., Van Ganse, E., et al.[2013]

A case report highlighted a potential adverse reaction in a child from paracetamol during a clinical trial comparing it to ibuprofen for orthodontic pain relief.

The report emphasizes the need for established protocols to manage adverse events in randomized clinical trials to ensure participant safety and effective response to unexpected reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Report of an adverse incident in a randomized clinical trial. McAlinden, RL., Ellis, PE., Sandy, JR.[2013]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12155800/

Vitamin C as an Adjuvant Analgesic Therapy in ... This study demonstrates that a high-dose vitamin C infusion lowered pain within the first 24 h after surgery and reduced early postoperative ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06306183

Effect of Vitamin C on Pain Reduction After an Emergency ... The investigators hypothesized that vitamin C will reduce pain intensity during a seven-day follow-up for ED discharged patients treated for acute MSK pain.

3. translational-medicine.biomedcentral.com translational-medicine.biomedcentral.com/articles/10.1186/s12967-017-1179-7

The role of vitamin C in the treatment of pain: new insights Overall, vitamin C appears to be a safe and effective adjunctive therapy for acute and chronic pain relief in specific patient groups.

4. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0316450

Impact of vitamin C on the reduction of opioid consumption for ... The literature suggests that administering vitamin C can reduce both pain and opioid consumption in the context of immediate postoperative acute pain (24 to 72 ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1878124124000601

Review article Efficacy of vitamin C supplementation in ... Conclusion. The results of our study showed the positive effect of VC supplementation in reducing the prevalence of CRPS-I after limb surgery.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5391567/

The role of vitamin C in the treatment of pain: new insights - PMC Overall, vitamin C appears to be a safe and effective adjunctive therapy for acute and chronic pain relief in specific patient groups.

7. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT06306183

Effect of Vitamin C on Pain Reduction After an Emergency ... Furthermore, vitamin C is safe and associated with very few adverse events. The primary objective of this study is to determine whether vitamin C can reduce ...

8. mayoclinic.org mayoclinic.org/drugs-supplements-vitamin-c/art-20363932

Vitamin C Safety and side effects. When taken at suggested doses by mouth, vitamin C supplements are mostly safe. Taking too much vitamin C can cause side ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S0007091221008527

Efficacy and safety of perioperative vitamin C in patients ... Vitamin C was associated with a reduction in postoperative pain score and cumulative morphine consumption up to 48 h after surgery.