Prevention of Post-Traumatic Contractures with Ketotifen II (PERK II)
Abstract
Objectives and Rationale: Loss of joint motion following joint injury, or post-traumatic contractures, is a common complication following fractures or dislocations. For people with post-traumatic elbow contractures, the limited motion interferes with feeding, dressing, grooming, and reaching, which markedly reduce the quality of life. Both in military and civilian populations, those affected are in the 20- to 60-year age group, greatly increasing the impact on productivity and return to work or duty. Our research has focused on the joint capsule, the critical structure that limits joint motion. The joint capsule connects the ends of the bones that form a joint and it is made of material like ligaments and tendons. We established in the joint capsule an increased number of mast cells, a cell type associated with inflammation, excessive scarring in burns of the skin, and asthma. A medication used for the chronic treatment of asthma, ketotifen, has been demonstrated in our laboratory to have promise in preventing post-traumatic contractures. These results are very exciting because ketotifen has a wide safety profile, is available as a pill, is low cost, and has been used in the chronic treatment of asthma for over 40 years. The objective of this study is to evaluate the use of ketotifen to prevent elbow joint motion loss in adult participants suffering fractures of the bones of the elbow or dislocation of the elbow joint. Participants will be randomly chosen to receive either ketotifen or a sugar pill for 6 weeks after injury. Participants will be followed at specified times and elbow range of motion will be measured, up to 1 year after the injury. Other measures of participant function, and fracture healing, will be collected. The main comparison will be to determine if elbow motion loss is prevented more in the ketotifen group when compared to the sugar pill group. Applicability and Impact of the Clinical Research: This proposal pertains to the Fiscal Year 2016 (FY16) Peer Reviewed Orthopaedic Research Program (PRORP) Clinical Trial Award (CTA) Focus Area on Surgical Care -- Extremity Fractures. This research optimizes patient outcomes through prevention of post-traumatic joint contractures following fractures. This research has direct relevance to civilians and military personnel suffering elbow injuries. Approximately 200,000 elbow fractures or dislocations occur in adults each year in the United States. Around 10%-15% of people with elbow fractures or dislocations (20,000-30,000) require surgery due to loss of elbow motion. In addition to preventing contractures following injury, surgery for established post-traumatic elbow contractures is another group where ketotifen could enhance motion improvement. This research is applicable to other conditions in civilians and military personnel where contractures can occur. Post-traumatic joint contractures happen with other upper-extremity (shoulder, wrist and hand) or lower-extremity joint injuries (hip, knee, and ankle). Preventing contractures after injury, or improving joint motion following surgery to reverse post-traumatic contractures in these joints would be indications to use ketotifen. Contractures form following joint replacement, especially the knee. Surgery to reverse the contractures following joint replacement could be another use for ketotifen. By preventing contractures, or reversing established contractures, of the joints of the upper extremity, function is maintained to allow reaching for or placing objects up high, to perform personal care around the face, and to grip objects or write. Lower-extremity function is maintained by preventing contractures or reversing established contractures that would interfere with walking, running, or kneeling. Ketotifen is an attractive medication because it has a wide safety profile. The commonest side effects are sedation and weight gain, which were minor. The weight gain is about 1-2 kilograms
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1710665
Entities
People
- Kevin A Hildebrand
Organizations
- United States Army
- University of Calgary