Effect of Vitamin C on Pain Reduction After an Emergency Department Visit (Vicamed)

Vitamin C for Acute Musculoskeletal Pain in Emergency Department Patients: A Triple-Blind Randomized Control Trial (VICAMED)

Musculoskeletal (MSK) injuries such as sprains, strains, bruises, and fractures are among the most common reasons people visit the emergency department. These injuries often cause significant pain in the first few days, making it difficult to move, work, or sleep. Usual pain medications like ibuprofen or acetaminophen can help, but they are not safe or effective for everyone. Some people cannot take them because of heart, kidney, stomach, or liver problems. Others still experience strong pain despite treatment. Because of these limits, some patients receive opioids, which can cause side effects and carry a risk of dependence. Safer and more accessible options are needed.

Vitamin C is widely known for supporting the immune system, but research suggests it may also help reduce pain and inflammation. Studies in surgical patients have shown that vitamin C can lower pain levels, reduce the need for opioids, and support healing. These effects may be linked to its antioxidant properties and its role in tissue repair. However, no study has tested whether vitamin C can help people with recent MSK injuries treated in the emergency department.

The VICAMED study aims to answer this question. Adults arriving with an MSK injury that occurred within the past 48 hours can participate if they have at least moderate pain. Participants are randomly assigned to receive either vitamin C or a placebo. The first dose is given in the emergency department, followed by twice daily capsules for three days. Pain is measured using a simple 0-100 scale, recorded in an electronic or paper diary. A follow-up on day six helps the research team understand each participant's recovery, medication use, and overall experience.

Vitamin C is inexpensive, widely available, and very safe at the doses used in this study. If it proves effective, it could offer a simple, low risk option to help patients manage pain after an MSK injury and reduce the need for opioids in emergency care.

Study Overview

• Status: Recruiting
• Conditions: Pain, Acute
• Intervention / Treatment: Dietary supplement: Vitamin C; Other: Placebo

Detailed Description

Background:

Acute musculoskeletal (MSK) injuries are a major cause of emergency department (ED) visits and frequently result in moderate to severe pain during the first days following presentation. First-line analgesics such as NSAIDs and acetaminophen have important contraindications and safety limitations, particularly in older adults and patients with comorbidities, underscoring the need for safe, accessible, opioid-sparing alternatives. Preclinical studies and postoperative trials suggest that vitamin C (ascorbic acid) may provide analgesic and anti-inflammatory effects through reduction of oxidative stress, protection of neural tissues, and enhanced collagen synthesis. Meta-analyses have reported reductions in postoperative opioid consumption, pain intensity, and inflammatory markers. However, no randomized controlled trial has evaluated vitamin C for acute traumatic MSK pain in the ED.

Objective:

The primary objective is to determine whether a single 900 mg oral dose of vitamin C reduces pain intensity one hour after administration compared with placebo in adults presenting with acute MSK injuries. The main secondary objective is to assess whether 900 mg of vitamin C taken twice daily for three days reduces the time-weighted sum of pain-intensity difference (SPID) over 72 hours.

Methods:

The VICAMED study is a multicentre, triple-blind, randomized, placebo-controlled trial conducted in three university-affiliated EDs in Canada. Eligible participants are adults aged ≥18 years with MSK pain ≤48 hours, triaged to ambulatory care, and reporting pain >3/10. Exclusion criteria include recent vitamin C use, active cancer, recent analgesic intake, chronic pain treatment, and contraindications such as oxalate nephropathy or interactions with cyclosporine or warfarin. Participants receive an initial 900 mg dose of vitamin C or placebo in the ED, followed by twice-daily dosing for three days. Pain intensity is measured using validated 0-100 visual analog scales through electronic or paper diaries. A structured day-six follow-up captures missing data, analgesic use, adverse events, and health-related quality of life (EQ-5D-5L). The primary analysis uses ANCOVA adjusting for site and fracture status. Secondary analyses evaluate SPID72, analgesic consumption, time to significant pain relief, time to pain-free, proportion of days with adequate relief, adverse events, and healthcare utilization.

Based on a minimal clinically important difference of 13 points on a 0-100 pain scale and prior variance estimates, 204 participants are required for the primary outcome. The sample size for SPID72 will be finalized using pilot study data currently being analyzed. The study is powered to detect clinically meaningful differences in both immediate and short-term pain trajectories.

Expected Results:

If vitamin C demonstrates analgesic efficacy in acute MSK injuries, it could represent a safe, inexpensive, widely accessible, and opioid-sparing therapeutic option for ED patients, including those unable to use NSAIDs or acetaminophen. Given its favourable safety profile and over-the-counter availability, vitamin C has strong potential for rapid clinical integration. The research team's established collaborations within national emergency medicine networks will support broad dissemination and facilitate implementation across Canadian EDs.

• Study Type: Interventional
• Enrollment (Estimated): 204
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Martin Marquis, MSc; Phone Number: 514-338-2222; Email: martin.marquis.cnmtl@ssss.gouv.qc.ca

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1Y 1J8
      • Not yet recruiting
      • The Ottawa Hospital - General and Civic Campus
      • Contact: Gabriel Sandino-Gold, BSc; Phone Number: 17709 613-798-5555; Email: gsandino@ohri.ca
  • Quebec
    • Lévis, Quebec, Canada, G6V 3Z1
      • Not yet recruiting
      • Hotel-Dieu De Levis
      • Contact: Emilie Coté, BSc; Phone Number: 418-835-7121; Email: Emilie.Cote.cisssca@ssss.gouv.qc.ca
      • Principal Investigator: Patrick Archambault, MD MSc
    • Montreal, Quebec, Canada, H4J 1C5
      • Recruiting
      • Hopital du Sacre-Coeur de Montreal
      • Contact: Chantal Lanthier, RN; Phone Number: 3318 514-338-2222; Email: chantal.lanthier@crhsc.rtss.qc.ca
      • Contact: Martin Marquis, MSc; Phone Number: 7584 514-338-2222; Email: martin.marquis@crhsc.rtss.qc.ca
    • Québec, Quebec, Canada
      • Not yet recruiting
      • CHU de Québec - Université Laval
      • Contact: Ariane Bluteau, MSc; Phone Number: 70542 418 525-4444; Email: ariane.bluteau@crchudequebec.ulaval.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years old
2. Presenting to the ED with acute MSK pain of ≤ 48 hours duration at triage
3. Verbal numerical rating scale pain intensity at triage of ≥ 4 on a 0-10 scale
4. Triaged to the ambulatory section of the ED
5. Able to communicate in French or English

Exclusion Criteria:

1. Usage of Vit C supplements in the last week
2. Active cancer
3. Treated with opioids for any pain within 24 hours prior to recruitment
4. Treatment for chronic pain
5. Unable to fill out a pain intensity diary or unavailable for follow-up
6. Allergy to milk (lactose in the placebo) or Vit C
7. Treated with cyclosporine or warfarin
8. Pre-existing oxalate nephropathy, liver cirrhosis or hemochromatosis
9. Hospitalized after clinician evaluation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vitamin C; 900 mg vitamin C taken orally twice a day	Dietary supplement: Vitamin C; 900 mg vitamin C taken orally twice a day (one in the morning and one in the evening) for a 3-day period after ED discharge for the treatment arm.
Placebo Comparator: Placebo; Placebo taken orally twice a day	Other: Placebo; Placebo taken orally twice a day (one in the morning and one in the evening) for a 3-day period after ED discharge for the treatment arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-weighted sum of the pain-intensity difference (SPID)	The primary outcome is the time-weighted sum of the pain-intensity difference (SPID) over the three-day treatment period on a 0-100 visual analog scale (VAS), where 0 is no pain and 100 the worst pain imaginable. The SPID accounts for both the magnitude of the pain change and its duration, producing a single value that reflects the patient's overall experience.	Three days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Consumption of as-needed pain medication	Participants will be asked the name and the total amount of pain medication taken during the three-day follow-up.	Three days
Percentage of days with adequate relief	To assess the proportion of days with adequate pain control, participants will answer a daily yes/no question regarding whether their pain was adequately relieved.	Six days
New analgesic prescriptions	Numbered and of new pain medication prescription received during follow-up, even opioids.	Three days
Adverse events	We will document during the day-six questionnaire if any of the following adverse events were experienced during the three-day period: nausea, vomiting, constipation, dizziness, drowsiness, sweating, weakness, or other adverse events.	Three days
Quantity of Healthcare visits	Participants will be asked about the number of all unscheduled or scheduled healthcare visits related to their initial pain condition during the day-6 questionnaire.	Six days
Difference in pain intensity	The main secondary outcome is the difference in pain intensity, also measured on a 0-100 visual analog scale (VAS), where 0 is no pain and 100 the worst pain imaginable, between groups one hour after taking the first study drug in the ED.	Three days
Time for significant pain relief	Time for significant pain relief, reported in hours, is define in a 50% reduction in pain intensity.	Six days
Time to pain-free	Time, reported in hours, when pain reach 0 on a 0-100 visual analog scale (VAS), where 0 is no pain and 100 the worst pain imaginable	Six days
Quality of life improvement at six days	Health-related quality of life will be assessed using the validated EQ-5D-5L questionnaire. EuroQol - five dimensions - 5 levels. It assesses five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) across 5 levels of severity-from no problems to extreme problems-providing a 5-digit health state profile used in clinical research and economic evaluations. Common Interpretation: 11111: Perfect health (Index 1.0). 55555: Worst health (lowest possible index).	Six days

Collaborators and Investigators

• Sponsor: Centre Integre Universitaire de Sante et Services Sociaux du Nord de l'ile de Montreal
• Collaborators: The Ottawa Hospital; Hopital de l'Enfant-Jesus
• Investigators: Principal Investigator: Raoul Daoust, MD MSc, Université de Montréal

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: February 28, 2024
• First Submitted That Met QC Criteria: March 5, 2024
• First Posted (Actual): March 12, 2024

Study Record Updates

• Last Update Posted (Actual): March 2, 2026
• Last Update Submitted That Met QC Criteria: February 27, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Pain; RCT; Vitamin C; NSAID; Emergency department
• Additional Relevant MeSH Terms: Neurologic Manifestations; Pathologic Processes; Disease Attributes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain; Emergencies; Acute Pain; Organic Chemicals; Carbohydrates; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Hydroxy Acids; Ascorbic Acid
• Other Study ID Numbers: 2024-2829

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: IPD could be shared upon request, upon approval by our institution.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No