Impact of Vitamin C on opioïd Consumption After an Emergency Department Visit for Acute Musculoskeletal Pain

Impact of Vitamin C on the Reduction of Opioid Consumption After an Emergency Department Visit for Acute Musculoskeletal Pain: A Double-Blind Randomized Control Trial Protocol

Recent evidence has shown that vitamin C has some analgesic properties and can therefore reduce opioids used during healing. Vitamin C analgesic effect has been explored mostly during the short-term postoperative context or in disease specific chronic pain prevention but not after acute musculoskeletal injuries, which are often seen in the emergency department (ED).

The study's primary aim is to compare the total morphine 5 mg equivalent pills consumed during a two-week follow-up between patients receiving vitamin C or a placebo after ED discharge for an acute musculoskeletal pain complaint.

The investigators will conduct a double-blind randomized placebo-controlled trial with 464 participants distributed in two arms, one group receiving 1 000 mg of vitamin C twice a day for 14 days and another one receiving a placebo. Participants will be ≥18 years of age, treated in ED for acute musculoskeletal pain present for less than 2 weeks, and discharged with an opioid prescription for home pain management. Total morphine 5 mg equivalent pills consumed during the two-week follow-up will be assessed via an electronic (or paper) diary. In addition, patients will report their daily pain intensity, pain relief, side effects, and other types of pain medication or other non-pharmacological approach (ice, heat, immobilization, etc.) used. Three months after the injury, participants will also be contacted to evaluate chronic pain development. The investigators hypothesized that vitamin C, compared to a placebo, will reduce opioid consumption during a 14-day follow-up for ED discharged patients treated for acute pain.

Study Overview

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

Detailed Description

Study Rationale Literature suggests that the administration of vitamin C has an effect in reducing pain and opioid consumption in the context of immediate postoperative acute pain. However, the investigators could not find evidence on the effectiveness of vitamin C administration after an ED visit in the context of acute pain, notably in trauma injuries like fractures, bruises, sprains, strains, etc. Previous studies have only evaluated pain relief and opioid use for the immediate postoperative period of 24 to 72 hours. Therefore, the investigators propose to evaluate the efficacy of a 14-day regiment of vitamin C given to ED patients discharged with an opioid prescription for acute musculoskeletal (MSK) pain on total opioid consumption after two weeks. The two-week period was chosen because it defines the usual acute pain time frame, during which need for analgesics including opioids is essentially resolved in most patients (88% of our previous study cohort). Furthermore, since vitamin C is also associated with less post-herpetic neuralgia and complex regional pain syndromes (CRPS), the investigators also propose to evaluate its impact on the incidence of chronic pain and CRPS at 3 months.

Study Objectives The primary aim is to compare the difference in the total morphine 5 mg equivalent pills consumed after a two-week follow-up between patients receiving vitamin C versus patients receiving a placebo during these two weeks.

The secondary aims are to compare the following between patients receiving vitamin C vs patients receiving a placebo: pain intensity trajectories, average pain relief during the two-week, side effects, total morphine 5 mg equivalent pills consumed after a two-week follow-up for each type of MSK pain (fracture, contusions, cervical pain, lower back pain, MSK pain at other sites), incidence of chronic pain (including CRPS) at 3 months globally and for each type of MSK pain, incidence of CRPS for limb fractures, and for a wrist fracture in particular at 3 months, and prevalence of opioid use at 3 months.

Study Design The investigators will conduct a multi-center, double-blind, randomized, placebo-controlled trial performed in two tertiary trauma care university-affiliated hospitals located in Montreal and in Quebec City (Quebec, Canada) with an annual census of 60,000 and 67,000 visits, respectively.

Participants and recruitment Consecutive patients (from 8 to 20h every day) diagnosed with an acute musculoskeletal pain complaint ongoing for less than two weeks and discharged from the ED with an opioid prescription will be approached by the treating clinician to participate in the study and obtain their verbal consent to be seen by a research assistant. The decision to prescribe opioids will be at the discretion of the treating physician, but included patients will receive a standardized prescription of 20 pills of morphine 5 mg based on our previous work. The research assistant will then verify the patient's inclusion and exclusion criteria, explain the research protocol, and obtain informed written consent. Patients will be assessed via a two-week electronic (or paper) diary and contacted 3 months after ED discharge.

Randomization method and blinding Eligible patients will be block randomized at the initial visit (via 1:1 ratio) to either 1 000 mg vitamin C taken orally twice a day or matching placebo, using a centralized randomisation web system. Allocation concealment will be in place to ensure that the investigator and the individual enrolling the subject into the study have no prior knowledge of group assignment. Since fractures are associated with more opioid consumption, randomization will be a stratified by fracture or not and centre. According to the centralized web system, an independent pharmacist will dispense pre-packed numbered bottles of either vitamin C or placebo capsules for each patient. Both will be dispensed an identical capsules and the pharmacist will be unaware of the trial-group assignments. Each participant will be assigned a number and received the capsules in the corresponding pre-packed bottle. Group allocation will be disclosed only after final analysis or at the request of the patient's treating clinician.

Study drug Vitamin C (ascorbic acid) is a vital nutrient; it helps form and maintain bones, skin, and blood vessels and has antioxidant properties. It is not produced by the human body but occurs naturally in fruits and vegetables and other foods. It is also available as supplement over the counter in pharmacies, supermarkets, and health supplements stores and online. For adults, the recommended daily amount of vitamin C is 65 to 90 milligrams (mg) a day (Recommended Dietary Allowances by the Government of Canada).

• Study Type: Interventional
• Enrollment (Estimated): 464
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Martin Marquis, MSc; Phone Number: 7584 514-338-2222; Email: martin.marquis.cnmtl@ssss.gouv.qc.ca

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H4J 1C4
      • Recruiting
      • Hopital du Sacre-Coeur de Montreal
      • Contact: Martin Marquis, MSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged 18 and over;
2. Treated in ED for acute musculoskeletal pain present for less than 2 weeks;
3. Discharged with an opioid prescription;
4. Speaks French or English.

Exclusion Criteria:

1. Opioid use 1 month prior to the ED visit;
2. Already taking vitamin C supplement;
3. Active cancer;
4. Treated for chronic pain;
5. Treated for opioid use disorder;
6. Unable to fill out diary or unavailable for follow-up;
7. Any allergy, intolerance or sensitivity to milk (lactose) or morphine
8. Treated with cyclosporin or coumadin
9. Pregnant or lactating (dosage > 1,800 mg not recommended. For women of child-bearing age and sexually active in the past 3 months, a urine pregnancy test will be performed.)

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
Placebo Comparator: Placebo; Matching placebo	Other: Placebo; Placebo taken orally twice a day (one in the morning and one in the evening) for a 14-day period after ED discharge for the treatment arm
Experimental: Vitamin C; 1 000 mg vitamin C taken orally twice a day	Dietary supplement: Vitamin C; 1000 mg vitamin C taken orally twice a day (one in the morning and one in the evening) for a 14-day period after ED discharge for the treatment arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in the total morphine 5 mg equivalent pills consumed	Compare the difference in the total morphine 5 mg equivalent pills consumed after a two-week follow-up between patients receiving vitamin C versus patients receiving a placebo during these two weeks.	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain intensity trajectories	Compare pain intensity trajectories, measured on an 11-point numerical rating scale (NRS) from 0 to 10 (0 is no pain and 10 worst pain imaginable), between both groups with group-based trajectory modelling.	14 days
Average pain relief	Patient's average pain relief during the two-week, measured on an 11-point numerical rating scale (NRS) from 0 to 10 (0 is no pain and 10 worst pain imaginable).	14 days
Number (%) of participants with side effects	Patients will report which of the following side effects were experienced during the 14-day period: nausea, vomiting, constipation, dizziness, drowsiness, sweating, weakness, or other side effects.	14 days
Total morphine 5 mg equivalent pills consumed for each type of musculoskeletal (MSK) pain	Fracture, contusions, cervical pain, lower back pain, MSK pain at other sites	14 days
Incidence of chronic pain (including complex regional pain syndrome (CRPS)) globally and for each type of MSK pain	Globally and for each type of MSK pain using pain disability index (PDI) or Budapest criteria	3 months
Incidence of CRPS for limb fractures, and for a wrist fracture	For these cases in particular using Budapest criteria	3 months
Prevalence of opioid use	Patients will be asked if they still consumed opioids at 3 months	3 months

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Daoust R, Paquet J, Williamson D, Huard V, Arbour C, Perry JJ, Emond M, Berthelot S, Archambault P, Rouleau D, Morris J, Cournoyer A. Impact of vitamin C on the reduction of opioid consumption for acute musculoskeletal pain: A double-blind randomized control pilot study. PLoS One. 2024 Dec 31;19(12):e0316450. doi: 10.1371/journal.pone.0316450. eCollection 2024.
• Daoust R, Paquet J, Chauny JM, Williamson D, Huard V, Arbour C, Emond M, Rouleau D, Cournoyer A. Impact of vitamin C on the reduction of opioid consumption after an emergency department visit for acute musculoskeletal pain: a double-blind randomised control trial protocol. BMJ Open. 2023 May 24;13(5):e069230. doi: 10.1136/bmjopen-2022-069230.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: September 20, 2022
• First Submitted That Met QC Criteria: September 22, 2022
• First Posted (Actual): September 27, 2022

Study Record Updates

• Last Update Posted (Actual): March 31, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Pain; Vitamin C; Emergency department; Opioids
• 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: 2023-2442

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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