Vitamin C for Acute Pain

(Vicamed Trial)

Overseen By Martin Marquis, MSc

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Hopital du Sacre-Coeur 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

546 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment Vitamin C for acute pain?

Research shows that Vitamin C can help reduce pain in various settings, such as after surgery, by lowering pain scores and reducing the need for pain medication. In cancer patients with bone metastases, Vitamin C was associated with a 50% reduction in pain and improved performance status. ^{1 2 3 4 5}

Is Vitamin C generally safe for human use?

The provided research articles do not contain specific safety data on Vitamin C (ascorbic acid) for human use. ^{6 7 8 9 10}

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

Vitamin C is unique for acute pain treatment because it can reduce pain and the need for opioids (strong painkillers) by acting as a cofactor in the production of natural pain-relieving peptides in the body. It is often administered intravenously (through a vein) in high doses, which is different from many other pain treatments that are taken orally. ^{4 11 12 13 14}

What is the purpose of this trial?

Emergency department (ED) clinicians often prescribe anti-inflammatory drugs (NSAIDs) to manage acute musculoskeletal (MSK) pain (e.g.: fracture, sprain, back pain). However, even short-term NSAIDs use can have significant gastrointestinal, cardiovascular, MSK and renal adverse effects. For this reason, some patients cannot take or tolerate NSAIDs. Recent evidence has shown that vitamin C has some analgesic and anti-inflammatory properties particularly in postoperative context and prevent specific types of chronic pain. 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 pain intensity during a seven-day period following an ED visit for acute MSK pain. The investigators propose to compare two groups of patients, one receiving 900 mg of vitamin C to another receiving a placebo, twice a day for seven days. Both groups will consume acetaminophen slow release 650 mg two pills every eight hours regularly. Naproxen 500 mg (NSAID) will be used as a rescue medication if the patient's pain is not relieved. Participants will be ≥18 years of age, treated in ED for acute MSK pain present for less than 48 hours with pain intensity at triage of ≥ 4 on a 0-10 numeric rating scale, and discharged by an ED clinician with an NSAIDs prescription without opioids. The level of pain intensity during a seven-day period will be assessed daily using an electronic or paper diary, as well as pain relief, pain medication consumption, and adverse events. Three months after the injury, participants will also be contacted to assess the presence of chronic pain. The investigators hypothesized that vitamin C will reduce pain intensity and chronic pain development at three months. This research could provide a safe alternative to patients who are unable to take NSAIDs. It may also contribute to the reduction of the burden associated with chronic pain development.

Research Team

Raoul Daoust, MD MSc

Principal Investigator

Université de Montréal

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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?

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+

Findings from Research

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]

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]

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]

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]

References

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

Palliative Vitamin C Application in Patients with Radiotherapy-Resistant Bone Metastases: A Retrospective Study. [2015]

2. 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]

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

The influence of vitamin C on the outcome of distal radial fractures: a double-blind, randomized controlled trial. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

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

5. Denmark pubmed.ncbi.nlm.nih.gov

Does the vitamin C level affect postoperative analgesia in patients who undergo orthognathic surgery? [2023]

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

Prospective observational study of adverse drug reactions to diclofenac in children. [2021]

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

Adverse event assessment, analysis, and reporting in recent published analgesic clinical trials: ACTTION systematic review and recommendations. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Single dose oral aspirin for acute postoperative pain in adults. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Report of an adverse incident in a randomized clinical trial. [2013]

10. England pubmed.ncbi.nlm.nih.gov

Risk factors for adverse events in analgesic drug users: results from the PAIN study. [2013]

11. England pubmed.ncbi.nlm.nih.gov

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

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

Ascorbic Acid in the Acute Care Setting. [2021]

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

Effect of Intravenous High Dose Vitamin C on Postoperative Pain and Morphine Use after Laparoscopic Colectomy: A Randomized Controlled Trial. [2019]

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

Inhibition of morphine analgesia by ascorbate. [2013]