Valentina Ivezaj, Ph.D. - US grants

Project Summary. Rates of obesity and severe obesity are expected to continue to rise to alarming levels. By 2030, over 51% of adults in the US are expected to have obesity with a 130% increase in severe obesity. These staggering rates and projected future increases are deeply concerning given the substantial disease and economic burden of obesity. As severe obesity rates continue to rapidly rise, the use of metabolic and bariatric surgeries (MBS) is expected to increase. MBS is the most effective treatment for severe obesity and results in impressive acute and long-term weight loss, as well as improvement of medical and psychosocial comorbidities. Yet, weight outcomes are markedly variable after MBS, suggesting that surgery alone is not enough for a sizeable subgroup with severe obesity. Weight regain after MBS is common and a major concern, particularly because weight regain is associated with recurring or even worsening medical comorbidities. Despite the need for ongoing obesity treatment after MBS due to the chronicity of obesity and risk for regain, there is little guidance as to what treatment(s) should be provided based on empirical data. In fact, no prospective studies or randomized controlled trials (RCTs) have examined the effectiveness of pharmacologic agents and very few (and limited) RCTs have examined behavioral weight loss (BWL) to enhance weight losses following MBS. Thus, rigorous RCTs combining pharmacological and manualized BWL treatment to enhance weight outcomes after MBS is an imperative next step to reduce personal and public health costs of obesity. To help fill this critical gap in the MBS field, the proposed RCT will test the effectiveness of a rigorous manualized BWL and a FDA-approved weight-loss agent (naltrexone+bupropion/NB), alone and in combination, for improvements in weight loss, cardiovascular risk factors, and psychosocial functioning. N=160 patients with obesity (BMI?30 or ?27 with a medical comorbidity) who underwent MBS and have suboptimal weight outcomes will be randomly assigned (double-blind) in balanced factorial (2 X 2) design, to one of four 24-week conditions: BWL+NB, BWL+Placebo, NB-only (No BWL), or Placebo-only (No BWL). Outcome variables were determined based on the leading rigorous weight loss RCTs for obesity with NB, NIH ADOPT guidelines, and conceptually-relevant variables for NB and BWL. Independent outcome assessments will determine outcomes after discontinuation of treatments through 18 months. The proposed RCT will provide important new clinical findings regarding the utility and effectiveness of pharmacotherapy and BWL for a rapidly growing obesity subgroup and will inform care models for managing chronic obesity to enhance outcomes after MBS. This will be the first RCT to 1) test any pharmacologic treatment for obesity after MBS; 2) examine BWL and NB, alone and in combination, for weight loss and associated features in patients who have undergone MBS; and 3) examine the durability of treatment effects from combined treatment modalities by including long-term follow-up assessments after treatment delivery.