Perioperative Vitamin C to Reduce Persistent Pain After Total Knee Arthroplasty

Chronic Pain Clinical Trial

— PROVISION  

Official title:

PeRiOperative VItamin C to Reduce perSistent paIn After tOtal kNee Arthroplasty (PROVISION): a Pilot Multicentre Randomized Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06123715
• Other study ID #: 23-5642
• Status: Recruiting
• Phase: Phase 2
• Start date: April 4, 2024
• Est. completion date: February 28, 2026

Study information

• Verified date: March 2024
• Source: University Health Network, Toronto
• Contact: James Khan, MD
• Phone: 416-340-4800
• Email: James.Khan[@]medportal.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

PROVISION is a multicentre, pilot, parallel-group, blinded, randomized controlled trial of 100 patients undergoing total knee arthroplasty surgery. Consented eligible patients will be randomized to receive vitamin C: 2000 mg taken orally within 4 hours of the start of surgery, followed by 500 mg of vitamin C taken twice daily from post-operative day 1 to day 56 (8 weeks). Patient in the control group will receive placebo lactose monohydrate capsules. Study medications will be prepared to look similar and labelled as per regulatory requirements. Patients will follow up on post-operative days 1-3, weeks 2,4,6, and 8 post-operatively, and at 3- and 12-months post-operatively to report on pain, opioid and analgesic consumption, medication adherence, adverse events, functional, mood, and quality of life outcomes.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: February 28, 2026
• Est. primary completion date: February 28, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients >18 years old
• Undergoing a unilateral or bilateral primary total knee arthroplasty for advanced osteoarthritis of the knee

Exclusion Criteria:

• TKA for infection (septic joint), fracture, ankylosing spondylitis, lupus, or psoriatic arthritis
• History of kidney stones, acute or chronic renal failure, hemochromatosis, or glucose-6-phosphate deficiency
• Unlikely to comply with follow-up (e.g., no fixed address, plans to move out of town)
• Language difficulties that would impede valid completion of questionnaires
• Planned staged bilateral TKA
• Treating surgeon deems patient inappropriate for inclusion in trial
• Any allergy or sensitivity to milk
• Pregnant or planning to become pregnant during the study

Related Conditions & MeSH terms

• Chronic Pain
• Knee Pain Chronic
• Pain, Postoperative
• Post Operative Pain

Intervention

Drug:
• Vitamin C
Drug: Patients in the intervention group will receive 2g Vitamin C orally within 4 hours of the start of the surgery followed by 500 mg of Vitamin C to be taken orally twice a day from post-op day1 to day 56.
• Placebo
Drug: Patients in the placebo group will receive identical placebo capsules taken orally within 4 hours of the start of the surgery followed by placebo capsules taken orally twice a day from post-op day 1 to day 56.

Locations

Country	Name	City	State
Canada	Mount Sinai Hospital	Toronto	Ontario
Canada	Sunnybrook - Holland Centre	Toronto	Ontario
Canada	Toronto Western Hospital	Toronto	Ontario

Sponsors (3)

Lead Sponsor	Collaborator
University Health Network, Toronto	Canadian Institutes of Health Research (CIHR), The Arthritis Society, Canada

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Study will determine feasibility of enrolling, recruiting, and follow-up with patients.	The study will assess the feasibility of enrolling, recruiting, and following-up with patients undergoing a primary total knee arthroplasty (TKA) through active monitoring of recruitment/enrollment rates on a monthly basis for a total of one year using excel trackers. The follow-up rate of patients will be assessed at 12 months based on completion of all 12 month questionnaires.	12 months
Primary	Clinical site compliance	Clinical site compliance with trial protocol will be determined based on number of protocol deviations at each site as logged on the deviation logs. This will be assessed on a monthly basis for a full year to maintain active monitoring of compliance.	12 months
Primary	Resource Assessment	This pilot study will help determine the resources required for larger definitive trial based on critical analysis of recruitment trackers to assess time spent on recruitment/enrollment.	12 months
Secondary	Prevalence of persistent pain	Pain intensity measured using 0-10 Numeric Rating Scale (NRS) scale at rest and movement	3 months and 12 months
Secondary	Qualities and characteristics of persistent pain	Pain qualities measured using the 0-10 scale of the Short Form McGill Pain Questionnaire 2 (SF-MPQ-2)	3 months and 12 months
Secondary	Persistent Neuropathic Pain	Neuropathic pain assessed on a binary scale of Yes or No using the Douleur Neuropathique 4 (DN4) symptoms interview	3 months and 12 months
Secondary	Acute and chronic analgesic consumption	Analgesic and oral morphine-equivalent opioid consumption	Day of surgery, post-operative day 1-3, 3 months, and 12 months
Secondary	Development of Complex Regional Pain Syndrome (CRPS)	Presence of CRPS measured by a physical assessment of sensory, vasomotor, sudomotor/edema, and motor/tropic categories using the Budapest Criteria	3 months and 12 months
Secondary	Physical function	Patient reported outcome measure to assess level of function, daily living activities and their affect on pain measured by answering 12 questions using the Oxford Knee Score (OKS)	3 months and 12 months
Secondary	Emotional functioning	Patients emotional functioning measured on a scale of 1-5 using the Profile of Mood States (POMS)	3 months and 12 months
Secondary	Postoperative cognitive impairment	Assessment of different cognitive domains such as attention, concentration, memory, language, conceptual thinking, calculations, and orientation out of a total score of 22 using Montreal Cognitive Assessment - Blind (MoCA-BLIND)	3 months
Secondary	Patient Satisfaction	Assessment of patient satisfaction with surgery on scale of 0-100	3 months and 12 months
Secondary	Quality of life assessment	Patient reported assessment of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression on a scale of level 1 - level 5 using the EuroQol 5-dimension 5-level (EQ-5D-5L)	3 months and 12 months
Secondary	Adverse events	Monitored as a secondary safety outcome using an assessment of follow-up visits for drug related adverse events and passive surveillance of clinical notes	3 months and 12 months