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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03652753
Recruitment Status : Active, not recruiting
First Posted : August 29, 2018
Last Update Posted : May 7, 2019
Sponsor:
Information provided by (Responsible Party):
Kyle Schweser MD, University of Missouri-Columbia

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.


Condition or disease Intervention/treatment Phase
Pilon Fracture Drug: N-acetylcysteine Drug: Saline Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Prevention of Cartilage Cell Death Following a Pilon Fracture With Intra-articular Injection of N-Acetylcysteine (Pilon NAC)
Actual Study Start Date : January 1, 2019
Estimated Primary Completion Date : January 2023
Estimated Study Completion Date : January 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Fractures

Arm Intervention/treatment
Experimental: N-acetylcysteine (NAC)
Injection of N-acetylcysteine at the time of external fixation
Drug: N-acetylcysteine
4 mL of a 20% solution of NAC will be injected into the ankle of patients with pilon fractures at the time of their external fixator surgery

Placebo Comparator: Saline
Injection of saline at the time of external fixation
Drug: Saline
4 mL of a 20% solution of saline will be injected into the ankle of patients with pilon fractures at the time of their external fixator surgery




Primary Outcome Measures :
  1. Cartilage Cell Viability [ Time Frame: At time of definitive surgery ]
    During the definitive surgery we will take a cartilage biopsy and analyze for cell viability.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03652753


Locations
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United States, Missouri
University of Missouri Health System
Columbia, Missouri, United States, 65212
Sponsors and Collaborators
University of Missouri-Columbia

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Responsible Party: Kyle Schweser MD, Assistant Professor, University of Missouri-Columbia
ClinicalTrials.gov Identifier: NCT03652753    
Other Study ID Numbers: 2011492
First Posted: August 29, 2018    Key Record Dates
Last Update Posted: May 7, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Fractures, Bone
Wounds and Injuries
Acetylcysteine
N-monoacetylcystine
Antiviral Agents
Anti-Infective Agents
Expectorants
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antidotes