Metreleptin in Anorexia Nervosa, Randomized Controlled Trial; Effects on Depressive Symptoms and Concomitant Changes in Brain Connectivity
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Clinician-rated depression on the 17 point Hamilton Depression Scale (HAMD-17) in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
研究概览
简要总结
The treatment of anorexia nervosa often proves to be difficult. There are no drugs that work specifically for the treatment of anorexia nervosa. Experimental administration of metreleptin (synthetically produced leptin) to patients with anorexia nervosa has produced positive results. This study tests the effect of metreleptin in comparison with placebo, which could potentially make treatment easier. The aim of the study is to investigate whether treatment with metreleptin can help to reduce the symptoms of anorexia nervosa and improve mood and weight.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 17 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Main key inclusion criteria:
- •Current diagnosis of AN according to fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) confirmed with Structured Clinical Interview for DSM-5 (SCID-5)
- •BMI > 13 kg/m2; BMI ≤ 18 kg/m2; body weight ≥ 35 kg
- •Hospitalisation in the Eating Disorders Unit, Department of Consultation-Liaison Psychiatry and Psychosomatic Medicine, University Hospital of Zurich
- •Ability to understand German language
- •Age range: 17 - 65 years
- •Depressive symptoms: HAMD-17 ≥ 8
- •Negative urine pregnancy test, non-lactating and double birth control
- •Informed Consent as documented by signature
排除标准
- •Illicit drug intake within last month; current alcohol use disorder
- •Severe psychiatric and/or severe somatic comorbidities; f. e. lifetime diagnosis of schizophrenia, bipolar disorder, inflammatory bowel disorders, diabetes mellitus, autoimmune disorders, pancreatitis, neurological disorders, cancer including lymphoma
- •Acute suicidality or current serious non-suicidal self-injury
研究组 & 干预措施
Metreleptin-assisted therapy
25 patients will receive a daily subcutaneous injection of metreleptin for 14 days.
The dose starts with 0.4 ml daily, and gradually increases until 1.8 ml; until 1.2 ml in male patients daily.
Placebo-therapy
25 patients will receive a daily subcutaneous injection of inactive substance (placebo) for 14 days. To ensure blinding, the dosing scheme of placebo will have the identical volume to the dosing scheme of metreleptin (verum).
干预措施: Sodium chloride (Drug)
结局指标
主要结局
Clinician-rated depression on the 17 point Hamilton Depression Scale (HAMD-17) in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
时间窗: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
HAMD-17 is a semi-structured interview and consists of 17 items assessing symptoms of depression from the perspective of the clinician. Possible scores range from 0 (no depressive symptom) to 4 (strong depressive symptom). The higher the total score, the more severe the depressive symptoms.
Body weight status in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
时间窗: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
Body weight status will be indicated by weight in kilograms (kg).
次要结局
- 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(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(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(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(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(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(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(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(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(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(Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49))
- Heart Frequency Variation (HFV) in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up(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(Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49))
- Blood chemistry in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up(Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49))
- Neuroendocrinological blood parameters in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up(Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49))
研究者
Gabriella Milos
Prof. Dr. med.
University of Zurich