Metreleptin in Anorexia Nervosa

Anorexia nervosa (AN) mainly affects young people, especially young women. AN is one of the most lethal psychiatric disorders. Treatment often proves to be very difficult, and the course of AN is frequently chronic. Specific pharmacological therapies for AN are lacking. Recent studies have shown that metabolic alterations play a major role in the etiology and pathogenesis of AN. An important metabolic alteration involved in the etiology and pathogenesis of AN is the hormone leptin. Patients with AN show hypoleptinemia. The role of hypoleptinemia in the neuroendocrine adaptation to starvation seems to induce emotional, cognitive, and behavioral symptoms of AN. From a theoretical point of view, pharmacotherapy aimed at increasing leptin levels in patients with AN has great therapeutic potential. Recently, positive effects following the experimental administration of subcutaneous metreleptin have been observed in small number of young patients with severe AN. Importantly, no side effects have been observed. For all these reasons, the present study will investigate, using a double-blind design, the therapeutic effect of metreleptin in patients with AN. Metreleptin will be administrated to 50 inpatients with AN: 25 patients will receive verum and 25 will receive placebo for 14 days. The primary objectives of this study are the amelioration of mood and weight. Secondary objectives are the investigation of functional brain connectivity, AN symptoms, as well as hematological, blood chemistry and neuroendocrinological parameters.

• Subjective depression by the Beck Depression Inventory-II (BDI-II) in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up [Срок оценки: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)]
• Functional brain connectivity in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up [Срок оценки: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)]
• Anorexia Nervosa psychopathology assessed by the Eating Disorders Examination Questionnaire (EDE-Q) in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up [Срок оценки: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)]
• External rated hyperkinesia assessed by the Structured Inventory for Anorexic and Bulimic Eating Disorders (SIAB, item 42) in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up [Срок оценки: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)]
• Subjective hyperkinesia assessed by the Exercise and Eating Disorders Questionnaire (EED) in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up [Срок оценки: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)]
• Autism symptoms assessed by the Autism-Spectrum Quotient-short version (AQ-k) in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up [Срок оценки: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)]
• Patient's quality of life by items 1, 2, 5, 6, 7, 10, 17, 19, 20, and 22 from the WHO Quality of Life Questionnaire (WHOQOL-BREF) in the metreleptin-assisted therapy group compared to placebo-therapy between Baseline, Post Treatment and 5 weeks Follow Up [Срок оценки: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)]
• Visual Analog Scale (VAS) about key Anorexia Nervosa and depression symptoms in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up [Срок оценки: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)]
• Social interaction by the Liebowitz Social Anxiety Scale (LSAS) in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up [Срок оценки: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)]
• Anhedonia by the Snaith-Hamilton Pleasure Scale (SHAPS-D) in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up [Срок оценки: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)]
• Hematology in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up [Срок оценки: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)]
• Hematology in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up [Срок оценки: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)]