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Recruiting Phase 4 NCT03652753

NCT03652753 Pilon Fracture With Intra-articular Injection of N-Acetylcysteine (Pilon NAC)

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Clinical Trial Summary
NCT ID NCT03652753
Status Recruiting
Phase Phase 4
Sponsor University of Missouri-Columbia
Condition Pilon Fracture
Study Type INTERVENTIONAL
Enrollment 30 participants
Start Date 2019-01-01
Primary Completion 2026-12

Eligibility & Interventions

Sex All sexes
Min Age 18 Years
Max Age N/A
Study Type INTERVENTIONAL
Interventions
N-acetylcysteineSaline

Eligibility Fast-Check

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What to Expect as a Participant

You will actively receive the study intervention — which may be a drug, biologic, device, or procedure.

Phase 4 studies follow an already-approved treatment in real-world conditions to monitor long-term safety and effectiveness.

This trial targets 30 participants in total. It began in 2019-01-01 with a primary completion date of 2026-12.

⚠ This information is for research awareness only. Always consult your physician before joining any clinical trial. Participation is voluntary and you may withdraw at any time.

Brief Summary

High energy intra-articular fractures of the distal tibia, or Pilon fracture, is a devastating injury with multiple short and long term complications. The incidence of these injuries is increasing as survival rates after motor vehicle collisions increase. The current standard of care for high energy pilon fractures is to place an external fixator at the time of injury and then provide definitive internal fixation when the soft tissue envelope allows, which is usually around 10-14 days. Arguably, the most debilitating long term complication after a high energy pilon fracture is the development of post-traumatic osteoarthritis (PTOA), which occurs in 50% or more of pilon fractures within the first 2 years of surgery. The development of osteoarthritis occurs even in the presence of adequate restoration of the tibial plafond. Part of this issue lies in the fact that ankle joint cartilage is the thinnest of any major articular joint and sustains a great deal of damage at the time of injury. This impaction and injury initiates a cascade of events that ultimately result in cartilage cell death, or chondrolysis. Chondrolysis occurs via necrosis or apoptosis. Apoptosis occurs via a caspase pathway, while necrosis of chondrocytes likely occurs secondary to overproduction of reactive oxidant species (ROS). Recent animal models have demonstrated several things: chondrocyte death is highest along fracture lines, and likely undergo necrosis as opposed to apoptosis. The reason that PTOA likely occurs in such a high percentage of pilon fractures is because of this chondrolysis, and if a method can be developed to decrease the rate of chrondrocyte necrosis, then the rate of PTOA could potentially improve and improve patient outcomes overall. A recent bovine model examined the injection of N-acetylcysteine (NAC) after an intra-articular knee fracture and its effect on the cartilage cell viability. Their study demonstrated that chondrocyte cell viability after an injection of NAC within four hours of injury decreased chondrolysis from roughly 60% to about 30% at 48hrs. The effect was greater the closer to injury the injection occurred, and was statistically significant for 2 weeks. This indicates that free radical scavengers can potentially improve cartilage cell viability and help prevent the development of PTOA. No studies have been published on humans regarding injection of NAC after a fracture. However, a recent article examined the injection of NAC into osteoarthritic knees and found that it was effective in lowering certain cartilage degradation markers and was comparable to hyaluronic acid for both pain and function. NAC has been proven safe for both intra-articular injections and systemic injections in humans. Our study will focus on the improvement of cartilage cell viability with an injection of NAC. Our hypothesis is that the NAC intra-articular injection will increase the percentage of viable cartilage cell after sustaining a pilon fracture, when compared to a placebo injection of saline. The goal of this study is to examine the effects of an intra-articular injection of the amino acid NAC on cartilage cells after an intra-articular fracture of the ankle joint. The long-term clinical goal of this research is to reduce the incidence of post-traumatic osteoarthritis in the ankle joint after fracture.

Eligibility Criteria

Inclusion Criteria: * Closed high energy pilon fracture requiring a staged procedure Exclusion Criteria: * Younger than 18 * Open fracture * Intra-articular injury not requiring a staged procedure * Allergy to NAC * Wounds preventing safe intra-articular injection * Unwilling to participate in the study * Pregnancy

Contact & Investigator

Central Contact

Vicki Jones, MEd, CCRP

✉ jonesvicki@health.missouri.edu

📞 (573) 882-7583

Frequently Asked Questions

Who can join the NCT03652753 clinical trial?

This trial is open to participants of all sexes, aged 18 Years or older, studying Pilon Fracture. Full inclusion and exclusion criteria are listed in the Eligibility Criteria section. Always confirm your eligibility with the research team before applying.

What phase is the NCT03652753 trial and what does that mean for participants?

Phase 4 studies are conducted after a treatment has been approved. They monitor long-term safety and real-world effectiveness in a broader patient population.

Is NCT03652753 currently recruiting?

Yes, NCT03652753 is actively recruiting participants. Contact the research team at jonesvicki@health.missouri.edu for enrollment information.

Where is the NCT03652753 trial being conducted?

This trial is being conducted at Columbia, United States.

Who is sponsoring the NCT03652753 clinical trial?

NCT03652753 is sponsored by University of Missouri-Columbia. The trial plans to enroll 30 participants.

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