Researchers on the Path to a Cure - Spotlight on Dr. Christian Lattermann
Osteoarthritis Center of Excellence Research Story
Over the last month, we’ve kept you updated on the work being done by the researchers in our osteoarthritis (OA) center of excellence (OA COE). The COE is currently funding three Clinical Trial Network demonstration studies that may lead to better diagnosis and earlier treatments for arthritis. Researchers from six different institutions will collaborate in various aspects of these cutting-edge studies. This is the last in a series of three blogs describing these studies.
Most people with partial or complete rupture of the anterior cruciate ligament (ACL) develop post traumatic OA (PTOA) within 10 to 20 years after their injury. Unfortunately, current ACL injury treatment options (both surgical and non-surgical) are successful in the short-term but do little or nothing to reduce the risk of developing PTOA later.
All three of the current OA COE are demonstration projects that build on knowledge gained from earlier foundation-funded ACL and PTOA research.
Dr. Lattermann and his team are basing their OA COE project on what they learned from an earlier Arthritis Foundation-funded study. In 2012, Dr. Lattermann received an Innovative Research Grant for his 2-year project, “ IL-1RA Treatment in Patients with Acute ACL Tear and Painful Effusions ,” which he worked on with Dr. Kraus. Due to unforeseen difficulties, this study was modified to use a corticosteroid (an anti-inflammatory agent) instead of a blocker of IL-1. The study was the first of its kind to evaluate the effect of an early anti-inflammatory intervention and biomarker profiles in the first couple of weeks after ACL injury. In brief, this study concluded that PTOA begins at the time of ACL injury. In this early study, 49 young adult patients were treated with corticosteroid or placebo at 4 days and 2 weeks following the ACL injury. The study showed that while early treatment with corticosteroid did reduce collagen breakdown in cartilage, it didn’t reduce the anti-inflammatory biomarkers (Interleukin-1 or IL-1) in patients.
Following the previous study, the team continued to work on the FDA approval to use an iL-1 blocker that we believe to be even more effective in blocking inflammation than cortisone. The current OA COE study is now looking at how this injectable drug (also known as IL‑1 receptor antagonist or IL-1Ra) may reduce the risk of developing PTOA in adolescents and young adults (aged 14 to 33) with ACL tears. The goal is that the drug will reduce the level of IL-1 in patients, thereby reducing the future risk of developing PTOA. IL-1Ra is currently used to treat rheumatoid arthritis , juvenile inflammatory arthritis , and post-surgical knee swelling. Dr. Lattermann and his team have received permission by the FDA to treat and study patients after ACL injury using IL-Ra.
Patients who take part in this study will be placed by random into one of three treatment groups:
Dr. Lattermann and his team will look at the changes in biomarkers in synovial fluid, blood, and urine at different times beginning within 7 days of the injury for up to 1 year. Knee imaging in the form of MRI scans and x-rays will also be performed for up to 2 years to look for changes.
By looking at biomarkers and knee imaging, researchers hope to pinpoint not only if the drug treatment may be effective, but also the best time to begin treatment to prevent further damage. About 60 patients are planned to be enrolled in this study, with the first patient starting in April.
Dr. Lattermann, the principal investigator, will coordinate the analyses with researchers at the University of California San Francisco and Duke University. Dr. Lattermann is currently a Professor for Orthopaedics and Sports Medicine at the UK College of Medicine (Department of Orthopaedic Surgery and Sports Medicine).
Over the last month, we’ve kept you updated on the work being done by the researchers in our osteoarthritis (OA) center of excellence (OA COE). The COE is currently funding three Clinical Trial Network demonstration studies that may lead to better diagnosis and earlier treatments for arthritis. Researchers from six different institutions will collaborate in various aspects of these cutting-edge studies. This is the last in a series of three blogs describing these studies.
Most people with partial or complete rupture of the anterior cruciate ligament (ACL) develop post traumatic OA (PTOA) within 10 to 20 years after their injury. Unfortunately, current ACL injury treatment options (both surgical and non-surgical) are successful in the short-term but do little or nothing to reduce the risk of developing PTOA later.
All three of the current OA COE are demonstration projects that build on knowledge gained from earlier foundation-funded ACL and PTOA research.
- Xiaojuan Li and her team of investigators are working to refine and standardize biomarker assessment in cartilage images obtained through magnetic resonance imaging (MRI) to allow earlier diagnosis.
- Virginia Byers Kraus and her team are working to identify which biomarkers are most critical for predicting risk of OA after injury and to confirm the earliest and best timepoints to start treatments.
- Christian Lattermann and his research team are working on establishing a clinical trials platform to put it all together in a demonstration project allowing for the exploration of new therapeutic strategies to prevent PTOA. This platform is designed to incorporate and further validate findings with regards to early biochemical biomarkers and (MRI) imaging biomarkers and patient reported outcomes (PROs) for pain and function.
Dr. Lattermann and his team are basing their OA COE project on what they learned from an earlier Arthritis Foundation-funded study. In 2012, Dr. Lattermann received an Innovative Research Grant for his 2-year project, “ IL-1RA Treatment in Patients with Acute ACL Tear and Painful Effusions ,” which he worked on with Dr. Kraus. Due to unforeseen difficulties, this study was modified to use a corticosteroid (an anti-inflammatory agent) instead of a blocker of IL-1. The study was the first of its kind to evaluate the effect of an early anti-inflammatory intervention and biomarker profiles in the first couple of weeks after ACL injury. In brief, this study concluded that PTOA begins at the time of ACL injury. In this early study, 49 young adult patients were treated with corticosteroid or placebo at 4 days and 2 weeks following the ACL injury. The study showed that while early treatment with corticosteroid did reduce collagen breakdown in cartilage, it didn’t reduce the anti-inflammatory biomarkers (Interleukin-1 or IL-1) in patients.
Following the previous study, the team continued to work on the FDA approval to use an iL-1 blocker that we believe to be even more effective in blocking inflammation than cortisone. The current OA COE study is now looking at how this injectable drug (also known as IL‑1 receptor antagonist or IL-1Ra) may reduce the risk of developing PTOA in adolescents and young adults (aged 14 to 33) with ACL tears. The goal is that the drug will reduce the level of IL-1 in patients, thereby reducing the future risk of developing PTOA. IL-1Ra is currently used to treat rheumatoid arthritis , juvenile inflammatory arthritis , and post-surgical knee swelling. Dr. Lattermann and his team have received permission by the FDA to treat and study patients after ACL injury using IL-Ra.
Patients who take part in this study will be placed by random into one of three treatment groups:
- Group 1 will receive a placebo injection at Visit 1(about 4 days after injury) and an IL-1Ra injection at Visit 2 (about 2 weeks after injury).
- Group 2 will receive an IL-1Ra injection at Visit 1and a placebo injection at Visit 2.
- Group 3 will receive placebo injections at Visits 1 and 2.
Dr. Lattermann and his team will look at the changes in biomarkers in synovial fluid, blood, and urine at different times beginning within 7 days of the injury for up to 1 year. Knee imaging in the form of MRI scans and x-rays will also be performed for up to 2 years to look for changes.
By looking at biomarkers and knee imaging, researchers hope to pinpoint not only if the drug treatment may be effective, but also the best time to begin treatment to prevent further damage. About 60 patients are planned to be enrolled in this study, with the first patient starting in April.
Dr. Lattermann, the principal investigator, will coordinate the analyses with researchers at the University of California San Francisco and Duke University. Dr. Lattermann is currently a Professor for Orthopaedics and Sports Medicine at the UK College of Medicine (Department of Orthopaedic Surgery and Sports Medicine).
