This proposal is in response to the NIH Program Announcement PAR16-446 titled ?NIAMS Clinical Trial Planning Grant (R34).? It is well known that obesity has been linked to many medical issues such as hypertension, diabetes and heart disease, as well as to early knee osteoarthritis. Large clinical trials, such as Look AHEAD (Action for Health in Diabetes), have shown that multicomponent weight loss interventions combining diet, physical activity, and behavioral modification are the most effective in achieving long-term weight loss (1, 2). As a result, clinical practice guidelines recommend the delivery of obesity interventions for numerous health conditions. The prevalence of the total knee replacement (TKR) surgical procedure has increased exponentially in the United States over the last few decades and overweight and obese patients are at particularly high risk of needing a TKR during their lifetime (3-5). A more alarming fact is that once an overweight or obese patient has undergone TKR, they are less likely to lose weight and are more likely to gain additional weight post-surgery. Unfortunately, with increases in BMI comes decreases in functionality of the TKR and greater likelihood of need for future revision of the current TKR in addition to need for TKR of the opposite limb (6). This unfortunate paradigm presents an accumulating disparity for the overweight and obese TKR patient population. Despite this ever-growing disparity, a void in the current literature examining the efficacy of long term weight loss in overweight and obese individuals who have undergone TKR persists. Therefore, it remains unknown if a multicomponent weight loss intervention would be beneficial to the subset of the overweight and obese population who have undergone TKR. To address this disparity, we propose a clinical trial planning grant to translate the successful Look AHEAD intensive lifestyle intervention (ILI) for use in overweight and obese post TKR patients, and to plan a future study to test whether the Look AHEAD ILI will result in significant weight loss in this at-risk population. We further propose to test whether these weight loss changes translate into functional improvements in the overweight and obese post TKR patient population compared to those receiving standard of care support and education alone. The planning grant will be conducted in 2 stages: a formative assessment stage (stage 1) and a, U01, clinical trial development stage (stage 2). During stage 1 we will modify the successful Look AHEAD ILI to be applied to the specific needs of the overweight and obese TKR patient population. During stage 2 we will outline the specific ILI modifications, develop the appropriate statistical analyses, and finalize our protocols utilizing information gathered via focus groups and key informant interviews to inform development the U01 clinical trial application. Given the epidemic proportion of overweight and obese patients requiring TKR surgery, we believe the health and economic impact of this study will be immeasurable.
The proposed clinical trial planning grant will develop the necessary components to conduct a prospective randomized clinical trial for weight loss in a population of overweight and obese patients who have undergone a total knee replacement. The results of the proposed trial will help inform patients, healthcare providers and the public and private-sector health care plans on ways to reduce the potential poor outcomes from overweight and obesity after total knee replacement surgery.
