Project Summary Background: Anorexia nervosa (AN) is a disorder of adolescence and young adulthood with a poor prognosis. Patients with medical instability and malnutrition are hospitalized to begin nutritional rehabilitation, or “refeeding”. Despite long hospitalizations, ~45% of patients are readmitted and only 18-55% recover in one year. Further, AN has the highest mortality of all psychiatric disorders (5.1%), similar to childhood cancers. These challenges make eating disorders a “common and costly” pediatric diagnosis 15. The overall goal of our research program is to improve these outcomes through novel approaches to refeeding. Our early work showed that the decades- old lower calorie refeeding approach was overly cautious and contributed to poor weight gain and protracted hospital stay. We developed and tested a Higher Calorie Refeeding (HCR) approach in preliminary studies showing improved outcomes with no apparent increase in risk. Clinical practice was eager to adopt HCR, an RCT was imperative. Our parent trial, StRONG, was the largest and only RCT of refeeding in the U.S. (R01HD082166; ClinicalTrials.gov NCT02488109). HCR restored medical stability 3.0 days earlier, with no increase in electrolyte abnormalities, and saved ~$20,000 in charges/participant. Proposed project: Since we began this research, “atypical” AN (AAN) was recognized as a new diagnosis describing AN at normal weight. This rapidly growing patient population comprised 42% our StRONG cohort. At baseline, they were equally malnourished and medically unstable as AN. The major finding motivating the proposed trial is that participants with AAN gained weight 40% slower and required >2 additional days in hospital to restore medical stability on HCR, as compared to AN. These signs of underfeeding were due to a suboptimal caloric “dose”. We have developed an Individualized Caloric Refeeding (ICR), which doses calories to weight consistent with other pediatric treatments (e.g. medication). Purpose, hypotheses and design: The primary purpose of the proposed trial (AIMs 1&2) is to compare the efficacy and safety of ICR to the new standard of care (HCR) in hospitalized patients with AAN. We hypothesize that ICR will restore medical stability faster than HCR with no increase in electrolyte abnormalities. After hospitalization, there is no consensus on clinical remission in AAN and controversy over whether these formerly overweight patients should gain weight to recover. We will examine metabolic, hormonal and psychological markers over 12 mo. (AIM 3), toward the goal of developing a definition of clinical remission in AAN. Based on our finding that Weight Suppression (WS) was a significant predictor of illness severity in AAN at admission, we hypothesize that WS during follow-up represents incomplete recovery from AAN. Design: RCT in N=74 patients with AAN, age 12-24 years, consented upon hospital admission, randomly assigned to ICR or HCR, and followed daily in hospital and at 3,6...