Effect of a Novel Intervention Targeting Appetitive Traits on Body Mass Index among Adults with Overweight or Obesity: A Randomized Clinical Trial

Importance: Behavioral weight loss (BWL) programs result in weight loss for some, but most individuals regain the weight. The behavioral susceptibility theory proposes that genetically determined appetitive traits, such as food responsiveness (FR) and satiety responsiveness (SR), interact with the environment and lead to overeating and weight gain; the regulation of cues (ROC) intervention was developed specifically to target FR and SR. Objective: To evaluate the efficacy of ROC, ROC combined with BWL (ROC+), BWL, and an active comparator (AC) over 12 months of treatment and 12 months of follow-up. Design, Setting, and Participants: This randomized clinical trial was conducted from December 2015 to December 2019 in a university clinic. A total of 1488 volunteers from the community inquired about the study; 1217 were excluded or declined to participate. Eligibility criteria included body mass index (BMI) of 25 to 45, age 18 to 65 years, and lack of comorbidities or other exclusionary criteria that would interfere with participation. Data were analyzed from September 2021 to January 2022. Interventions: ROC uniquely targeted FR and SR. BWL included energy restriction, increasing physical activity, and behavior therapy techniques. ROC+ combined ROC with BWL. AC included mindfulness, social support, and nutrition education. Main Outcomes and Measures: Change in body weight as measured by BMI. Results: A total of 271 adults (mean [SD] age, 46.97 [11.80] years; 81.6% female [221 participants]; mean [SD] BMI, 34.59 [5.28]; 61.9% White [167 participants]) were assessed at baseline, midtreatment, posttreatment, and 6-month and 12-month follow-up. Sixty-six participants were randomized to AC, 69 to ROC, 67 to ROC+, and 69 to BWL. Results showed that ROC, ROC+, and BWL interventions resulted in significantly lower BMI at the end of treatment (BMI ROC, -1.18; 95% CI, -2.10 to -0.35; BMI ROC+, -1.56; 95% CI, -2.43 to -0.67; BMI BWL, -1.58; 95% CI, -2.45 to -0.71). Compared with BWL, BMI at the end of treatment was not significantly different from ROC or ROC+ (BMI ROC, 0.40; 95% CI, -0.55 to 1.36; BMI ROC+, 0.03; 95% CI, -0.88 to 0.93); however, the BMI of the AC group was substantially higher (BMI AC, 1.58; 95% CI, 0.72 to 2.45). BMI reductions at 24 months after randomization were similar for ROC, ROC+, and BWL. Importantly, FR was a moderator of treatment effects with more weight loss for participants who scored higher in FR in the ROC and ROC+ groups. Conclusions and Relevance: These findings suggest that ROC and ROC+ provide alternative weight loss approaches for adults. These models could be particularly effective for individuals who struggle with FR and could be used as a precision approach for weight loss. Trial Registration: ClinicalTrials.gov Identifier: NCT02516839.