Prevention of Posttraumatic Contractures with Ketotifen (PERK)
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 20-60 year age group, greatly increasing the impact on productivity and return to work or duty. Our research has shown changes in 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 similar to ligaments and tendons. The identified change is increased numbers of mast cells, a particular 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 loss of motion after joint injury. 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 30 years in humans. 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 consenting to enter the study 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 of the Clinical Research: 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. This research will be applicable to all people who suffer elbow fractures or dislocations in civilian and military populations. Post-traumatic joint contractures occur with other joint injuries of the upper extremity (shoulder, wrist, and hand) or lower extremity (hip, knee, and ankle). Contractures form following joint replacement, especially the knee. In these instances (joint injury or surgery for joint replacement), the onset of the condition is easily defined and ketotifen could be taken to prevent contracture formation. Our research shows that ketotifen has to be taken within 1 week of the injury or surgery to be effective. By preventing 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 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 in studies where ketotifen was used for 12-32 weeks. In this research proposal, ketotifen will be used only for 6 weeks. In studies comparing ketotifen to sugar pill controls, the incidence of sedation was similar in both groups. Overdoses of 10-120 milligrams have been reported that were managed successfully with supportive measures only. There have been no reports of death following overdose. Ketotifen is not used when people are taking oral medications to treat diabetes or if participants have a history of seizures. Ketotifen does not cause birth defects. It is not recommended t
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510605
Entities
People
- Kevin A Hildebrand
Organizations
- United States Army
- University of Calgary