Clinical trial NCT06305182: Metreleptin in Anorexia Nervosa
Official title: Metreleptin in Anorexia Nervosa, Randomized Controlled Trial; Effects on Depressive Symptoms and Concomitant Changes in Brain Connectivity
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Anorexia Nervosa
Keywords: Anorexia Nervosa
Leptin
Metreleptin
Weight gain
Depression
Lead sponsor: University of Zurich
Sponsor class: OTHER
First posted: 2024-03-12
Enrollment: 50
Sex: ALL
Minimum age (years): 17
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Placebo-controlled, double-blind, randomized trial. The efficacy of Metreleptin in Anorexia Nervosa patients will be tested against an inactive Placebo.
Primary purpose: TREATMENT

Brief summary: 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 AN course is frequently chronic. Specific pharmacological therapies for AN are lacking. Recent studies have shown that metabolic alterations play a great role in the etiology and pathogenesis of AN. An important metabolic alteration playing a role 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 augmenting leptin levels in patients with AN have a great therapeutic potential. Recently, positive effects with experimental administration of subcutaneous metreleptin in few young patients with severe AN have been observed. Importantly, no side effects have been observed. For all these reasons, the present study will investigate - with a double blind design - the therapeutic effect of metreleptin in patients with AN. Metreleptin will be administrated to 50 AN-inpatients: 25 patients will receive verum and 25 will receive placebo during 14 days. 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 hematologic, blood chemistry and neuroendocrinological hormones.

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 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

Primary outcomes:
measure: 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
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Body weight status in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
Secondary outcomes:
measure: 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
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Functional brain connectivity in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: 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
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: 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
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: 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
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: 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
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: 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
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: 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
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: 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
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: 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
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Hematology in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Hematology in the metreleptin-assisted therapy group compared to placebo-therapy group between
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Hematology in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Hematology in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Hematology in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Blood chemistry in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Blood chemistry in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Blood chemistry in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Blood chemistry in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Blood chemistry in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Blood chemistry in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Blood chemistry in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Blood chemistry in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Blood chemistry in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Blood chemistry in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Blood chemistry in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Blood chemistry in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Blood chemistry in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Blood chemistry in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Blood chemistry in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Blood chemistry in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Blood chemistry in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Blood chemistry in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Blood chemistry in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Neuroendocrinological blood parameters in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Neuroendocrinological blood parameters in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Neuroendocrinological blood parameters in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Neuroendocrinological blood parameters in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Neuroendocrinological blood parameters in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Neuroendocrinological blood parameters in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Neuroendocrinological blood parameters in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Neuroendocrinological blood parameters in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Neuroendocrinological blood parameters in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Neuroendocrinological blood parameters in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Neuroendocrinological blood parameters in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Neuroendocrinological blood parameters in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Neuroendocrinological blood parameters in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Neuroendocrinological blood parameters in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Neuroendocrinological blood parameters in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Neuroendocrinological blood parameters in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Neuroendocrinological blood parameters in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Neuroendocrinological blood parameters in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Neuroendocrinological blood parameters in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Neuroendocrinological blood parameters in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Neuroendocrinological blood parameters in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Neuroendocrinological blood parameters in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Neuroendocrinological blood parameters in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Neuroendocrinological blood parameters in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Neuroendocrinological blood parameters in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Neuroendocrinological blood parameters in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
measure: Heart Frequency Variation (HFV) in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up
timeFrame: Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)
Other outcomes:
Locations:
city: Zurich
country: Switzerland
facility: Eating Disorder Unit, Clinic of Consultation-Liaison Psychiatry and Psychosomatic Medicine, University Hospital Zurich
Study officials:
References: