Chronic PainPhase 2PROVISIONNCT06123715
Perioperative Vitamin C to Reduce Persistent Pain After Total Knee Arthroplasty
A Phase 2 study testing Vitamin C in people with Chronic Pain and Knee Pain Chronic, run by University Health Network, Toronto at 3 sites in Canada.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Pain, Knee Pain Chronic, Post Operative Pain
- What is being tested?
- Vitamin C
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 400 participants
- Where
- 3 sitesCanada
- Study dates
- 16 Apr 2024to 31 Dec 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients >18 years old
- Undergoing a unilateral or bilateral primary total knee arthroplasty for advanced osteoarthritis of the knee
Who cannot join
- 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
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Canada3 sites, 3 recruiting
- Recruiting
Sunnybrook - Holland Centre
Toronto, Ontario, M4Y 1H1
Raman Mundi, MD, Raman.Mundi@medportal.ca
- Recruiting
Mount Sinai Hospital
Toronto, Ontario, M5G 1X5
James Khan, MD, James.Khan@medportal.ca
- Recruiting
Toronto Western Hospital
Toronto, Ontario, M5T 2S8
Anuj Bhatia, MD, Anuj.Bhatia@uhn.ca
About this study
Official title: PeRiOperative VItamin C to Reduce perSistent paIn After tOtal kNee Arthroplasty (PROVISION): a Pilot Multicentre Randomized Controlled Trial
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.
Read the detailed description
PROVISION is a multicentre, pilot, parallel-group, blinded, randomized controlled trial of 400 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.
- Conditions
- Chronic Pain, Knee Pain Chronic, Post Operative Pain
- Being tested
- Vitamin C, Placebo
- Medical subject headings
- Chronic Pain, Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin CDrug
Also called Ascorbic Acid
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.
PlaceboDrug
Also called Lactose (Monohydrate)
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.
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Experimental | Preoperative Vitamin C capsules Receives: Drug: Vitamin C |
| Placebo | Placebo comparator | Preoperative placebo capsules Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months
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.
Measured: 12 months
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.
Measured: 12 months
Secondary outcomes (10)
Prevalence of persistent pain
Pain intensity measured using 0-10 Numeric Rating Scale (NRS) scale at rest and movement
Measured: 3 months and 12 months
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)
Measured: 3 months and 12 months
Persistent Neuropathic Pain
Neuropathic pain assessed on a binary scale of Yes or No using the Douleur Neuropathique 4 (DN4) symptoms interview
Measured: 3 months and 12 months
Acute and chronic analgesic consumption
Analgesic and oral morphine-equivalent opioid consumption
Measured: Day of surgery, post-operative day 1-3, 3 months, and 12 months
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
Measured: 3 months and 12 months
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)
Measured: 3 months and 12 months
Emotional functioning
Patients emotional functioning measured on a scale of 1-5 using the EQ-5D-5L
Measured: 3 months and 12 months
Patient Satisfaction
Assessment of patient satisfaction with surgery on scale of 0-100
Measured: 3 months and 12 months
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)
Measured: 3 months and 12 months
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
Measured: 3 months and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2023
- Study start16 Apr 2024
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic PainStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), The Arthritis Society, Canada
- Responsible party
- Sponsor
- Investigators
- James Khan, MD, Principal investigator, University Health Network; Department of Anesthesia and Pain MedicineRaman Mundi, MD, Principal investigator, Holland Orthopedic and Arthritic CentreHarman Chaudhry, MD, Principal investigator, Holland Orthopedic and Arthritic CentreJesse Wolfstadt, MD, Principal investigator, Mount Sinai Hospital; Department of Surgery
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06123715
- Sponsor's protocol ID
- 23-5642
- Acronym
- PROVISION
- Status last verified
- Jun 2026
- First submitted
- 10 Oct 2023
- Last updated
- 23 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PeRiOperative VItamin C to Reduce perSistent paIn After tOtal kNee Arthroplasty (PROVISION): a Pilot Multicentre Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT06123715
- Acronym / sponsor ID
- PROVISION / 23-5642
- Conditions
- Chronic Pain, Knee Pain Chronic, Post Operative Pain
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), The Arthritis Society, Canada
- Study start
- 16 Apr 2024 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 9 Nov 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PROVISION is a multicentre, pilot, parallel-group, blinded, randomized controlled trial of 400 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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention | Experimental | Drug: Vitamin CPreoperative Vitamin C capsules |
| Placebo | Placebo comparator | Drug: PlaceboPreoperative placebo capsules |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients >18 years old
- Undergoing a unilateral or bilateral primary total knee arthroplasty for advanced osteoarthritis of the knee
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vitamin CAlso: Ascorbic AcidDrug: 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. | Drug | Intervention |
| PlaceboAlso: Lactose (Monohydrate)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. | Drug | Placebo |
Primary outcome
Study will determine feasibility of enrolling, recruiting, and follow-up with patients.
Time frame: 12 months
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.
Clinical site compliance
Time frame: 12 months
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.
Resource Assessment
Time frame: 12 months
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.
10 secondary outcomes
Prevalence of persistent pain
Time frame: 3 months and 12 months
Qualities and characteristics of persistent pain
Time frame: 3 months and 12 months
Persistent Neuropathic Pain
Time frame: 3 months and 12 months
Acute and chronic analgesic consumption
Time frame: Day of surgery, post-operative day 1-3, 3 months, and 12 months
Development of Complex Regional Pain Syndrome (CRPS)
Time frame: 3 months and 12 months
Physical function
Time frame: 3 months and 12 months
Emotional functioning
Time frame: 3 months and 12 months
Patient Satisfaction
Time frame: 3 months and 12 months
Quality of life assessment
Time frame: 3 months and 12 months
Adverse events
Time frame: 3 months and 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
James Khan, MD principal investigator
University Health Network; Department of Anesthesia and Pain Medicine
Raman Mundi, MD principal investigator
Holland Orthopedic and Arthritic Centre
Harman Chaudhry, MD principal investigator
Holland Orthopedic and Arthritic Centre
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Vitamin C in people with Chronic Pain and Knee Pain Chronic, run by University Health Network, Toronto at 3 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 23 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact James Khan, MD (416-340-4800 ext. 3243, James.Khan@medportal.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Study will determine feasibility of enrolling, recruiting, and follow-up with patients. (time frame: 12 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jun 2026.