Patients with Anorexia Nervosa (AN) can become medically unstable due to malnutrition and require hospitalization for nutritional rehabilitation, r refeeding. Despite these expensive and lengthy hospitalizations, rates of clinical remission are low. Up to 43% of patients will be re-hospitalized within one year. Studies seeking to improve these outcomes have identified rapid early weight gain as a predictor of 12 mo. recovery. Unfortunately, the currently recommended approach to refeeding in AN is associated with poor weight gain. This approach, Lower Calorie Refeeding (LCR), typically starts around 1200 calories per day and advances slowly by 200 calories every other day. It is intended to minimize risk for the refeeding syndrome, characterized by rapid shifts in fluids and electrolytes in response to nutrients. Since cases of cardiac failure, delirium and death associated with this syndrome were documented, LCR has been adopted as the standard of care in AN to ensure safety. Our recent studies demonstrate that this start low and go slow approach contribute to initial weight loss and prolonged hospitalization, now known as the underfeeding syndrome. We subsequently reported faster weight gain and shorter hospital stay using Higher Calorie Refeeding (HCR). Although we did not observe any cases of the refeeding syndrome, the safety of HCR has not been tested. This line of work is being rapidly translated into clinical practice. Some programs are implementing HCR despite major gaps in the evidence. The proposed RCT will address these gaps and facilitate the development of evidence-based approaches to refeeding in AN. Overall objective: The purpose of the proposed study is to compare the efficacy, safety and cost-effectiveness of LCR vs. HCR in hospitalized adolescents with AN.
Aims : (1) We will compare the efficacy of LCR vs. HCR in achieving and maintaining clinical remission, defined as both weight and cognitive recovery, and, secondarily, medical stability defined chiefly as waking heart rate > 50 bpm. (2) We will not confirm the safety of HCR, but will compare electrolyte disturbances associated with the refeeding syndrome. (3) Finally, we will compare the direct and indirect costs per adolescent recovered. Our overarching hypothesis is that HCR will result in earlier achievement of remission and medical stability. Design: This randomized controlled trial will assign participants to HCR or LCR refeeding within two clinical research centers when they are admitted to hospital for malnutrition due to AN. A total of 120 participants will be enrolled and followed prospectively during hospitalization in the Adolescent and Young Adult Eating Disorder Programs at UCSF Benioff Children's Hospital and Lucile Packard Children's Hospital. Participants will return for five follow-up visits over one year following discharge. We will retain at least 85% of participants at one year. UCSF will house the Data Coordination Center (DCC) separately from the clinical sites. Significance: Weight gain in hospital is crucial for long-term recovery from AN; this study is needed to develop evidenced-based recommendations for refeeding in this malnourished patient population.

Public Health Relevance

Anorexia Nervosa (AN) is a deadly illness with current treatment recommendations that are consensus-based and linked to poor outcomes. The proposed randomized controlled trial will compare the efficacy, safety and cost-effectiveness of two refeeding protocols in achieving short- and long-term recovery in AN adolescents hospitalized with malnutrition due to AN. These findings will provide much needed evidence to support the development of evidence-based approaches to clinical care for patients suffering from AN.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Study Section
National Institute of Child Health and Human Development Initial Review Group (CHHD)
Program Officer
Winer, Karen
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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