Anxiety-metabolism networks in human anorexia nervosa: Responses to caloric and non-caloric meals in the Networks Integrating Anxiety and Metabolism in Anorexia Nervosa (NAMA) randomized trial.

Anorexia nervosa (AN) is an eating disorder that is mediated by psychological and metabolic factors, yet it is unclear how these factors interact. The NAMA trial objective is to clarify the metabo-psychiatric interaction and identify how it affects AN patients' behaviour. This randomised trial will recruit thirty-six treatment-naïve female AN patients, 13-18 years of age, and thirty-six matched healthy controls. Participants will undergo psychiatric assessments followed by 12-h overnight fasting. The next morning, baseline assessments of outcomes will be performed. Patients will be randomly allocated 1:1 to receive a mixture with calories or receive a mixture without calories. Healthy controls will also be allocated to receive mixtures with/without calories. Mixtures will be standardised for taste and appearance, and allocation will be masked. The primary outcome measure is resting-state functional MRI 60 min post-consumption of the mixture. Secondary outcomes include (1) blood samples to study markers reflecting metabolic states, hunger/satiety and stress responses, (2) psychometric evaluations of subjective experiences and (3) assessment, in a second meal 3 h later, of the effects of previous calorie intake on subsequent food consumption. This article describes the study protocol, including the analysis plan, for a randomised controlled trial to comprehensively evaluate the effects of calorie intake in AN. The trial will distinguish psychological and metabolic neuronal networks associated with food intake and uncover how their integration affects food intake and other hallmark symptoms in AN. The aim is to accelerate treatment development by identifying brain mechanisms that drive AN.