The proposed work is directly responsive to the Fiscal Year 2017 Peer Reviewed Orthopaedic Research Program (PRORP) Applied Research Award, addressing the Soft Tissue Trauma Focus Area by proposing to develop a treatment for hand tendon injury that will optimize functional recovery and return to duty. Complex flexor tendon repair is required to restore function in complex injuries to the hand, but complications are common. The proposed project will develop a bio-lubricant that reduces a frequent complication of flexor tendon repair—scar formation on the tendon and between the tendon and its protective layer. By reducing scar development and improving digit function, this project will optimize Service members' return to duty and quality of life.
Hand trauma is a common injury sustained by Service members in active combat and in noncombat-related injuries in combat zones, during training, or in sport. Flexor tendon injuries, in which Service members often experience concurrent damage to bones, vessels, and nerves, are particularly difficult to manage. Surgical repair is the only treatment option, and complications during healing are common, particularly when repaired tendons must be immobilized following surgery. Scars on the tendons are the most common complication following flexor tendon reconstruction. After injury, even small scars between the tendons and pulleys can limit the ability of the tendon to move the finger. Long recovery times and limited final range of motion following flexor tendon trauma can restrict functionality and employment options for patients. These limitations can be severe enough to warrant medical discharge from the military. These injuries are not rare; we estimate that the incidence of cases requiring tenolysis (surgery to release a tendon affected by scarring) or tendon reconstruction after injury is roughly 100,000 affected individuals per year in the United States.
To improve patient outcomes, our team has developed a bio-lubricant that can increase the tendon's gliding ability and reduce the formation of scars. The proposed carbodiimide-derivatized hyaluronic acid (cd-HA) gel will provide an option for surgeons to help patients avoid debilitating scarring. The objective of this proposal is to test the safety and effectiveness of the cd-HA gel and its associated delivery device in a large animal model of flexor tendon injury, repair, and recovery using a turkey model. The results of this study are necessary to demonstrate feasibility and efficacy to the U.S. Food and Drug Administration (FDA) so that our team may pursue the first study of this compound in human subjects. We hypothesize that the cd-HA gel will safely reduce scar formation and improve digit function following tendon repair associated with post-operative immobilization, compared to the non-lubricated standard of care. The long-term goal of this program is to have this lubricant approved for clinical use, and we propose to complete work proposed here by mid-2021 to support the FDA Investigational Device Exemption application to initiate testing in humans. At the same time, we plan to submit for funding of Phase 1 clinical testing, either from PRORP and/or internal Mayo Clinic funds. While we cannot predict when FDA approval might be forthcoming, we can assert that a Phase 1 study in 10 patients to examine safety and dosage could begin immediately thereafter. We estimate that the Phase 1 study would take roughly 1 year to complete. If the Phase 1 trial confirms the safety of the product, then Phase 2 and 3 trials in up to 50 patients could follow.
These studies would be conducted at multiple sites, including military treatment facilities if possible, and would occupy 1 to 2 years for the purpose of examining efficacy, side effects, and adverse reactions. Funding would again be either from PRORP and/or internal Mayo Clinic funds, or, we hope—given a successful Phase 1 study and FDA approval—from commercial/venture start-up funds. Following successful completion of the Phase 3 trials, we will apply again to the FDA for approval for full clinical release, with manufacture either continuing at Mayo or by license to a separate (either existing or start-up) business. Ideally, by 2025, this product would be available commercially.
The cd-HA gel offers the potential for faster and more comprehensive recovery for flexor tendon trauma patients in the military, Veteran, and civilian health care systems. The gel has the potential to improve the daily functioning of Service members and/or Veterans who have sustained combat-related or non-battle orthopaedic hand injuries, restoring their readiness or return to duty/work and improving their quality of life. Benefits of the gel can also be experienced by families, caregivers, and members of the general public with flexor tendon injuries, and it may be applicable for other orthopaedic indications.
|Effective start/end date||1/1/17 → …|
- Congressionally Directed Medical Research Programs: $812,477.00