Metreleptin in Anorexia Nervosa
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Metreleptin, Sodium chloride.
- Who it may be relevant to
- Registry conditions: Anorexia Nervosa. Basic parameters: 17 years — 65 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Switzerland
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Metreleptin in Anorexia Nervosa, Randomized Controlled Trial; Effects on Depressive Symptoms and Concomitant Changes in Brain Connectivity
Overview
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.
Detailed description
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.
Interventions
- Drug Metreleptin
Metreleptin 3 mg is packaged in 3 ml Type I glass vials with chlorobutyl rubber stoppers, and aluminum seals with plastic flip-off caps. The vials are stored in refrigerator (2 - 8°C) and protected from light. Metreleptin for injection is a sterile, white, solid lyophilised cake. Prior to patient use, the content of a vial is reconstituted with 0.6 ml of water for injection for a final formulation of 10 millimolar (mM) glutamic acid, 2% glycine, 1% sucrose, 0.01% polysorbate 20, potential hydro - Drug Sodium chloride
The placebo will consist of sterile 0.9% saline (Sodium chloride), drawn up from a 10 ml i.v. vials. The placebo will be administered as an subcutaneous injection in an identical procedure as the metreleptin verum.
Primary outcome measures
- 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 [Time frame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)]
- Body weight status in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up [Time frame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)]
Secondary outcome measures (12)
- 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)]
Eligibility criteria
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
Main key exclusion criteria:
- 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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Quadruple blind
- Primary purpose
- Treatment
Study locations
Switzerland · 1 center
- Eating Disorder Unit, Clinic of Consultation-Liaison Psychiatry and Psychosomatic Medicine — Zurich
Identifiers
NCT: NCT06305182 · BASEC 2022-01328