Metreleptin in Anorexia Nervosa
- Registration Number
- NCT06305182
- Lead Sponsor
- Gabriella Milos
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 50
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo-therapy Sodium chloride 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).
- Primary Outcome Measures
Name Time Method 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 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 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).
- Secondary Outcome Measures
Name Time Method 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) Assessed with ECG and will be analysed with the software HRVTool in Matlab.
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) Measured with TNF-Alpha (unit TBD).
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) The Beck Depression Inventory-II is a self-report rating inventory that measures characteristic attitudes and symptoms of depression with 21 items, ranging from 0 (no depressive symptoms) to 3 (strong depressive symptoms). The higher the total score, the more severe the depressive symptoms.
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) For assessment of intrinsic functional connectivity in the brain, functional MRI images will be acquired for each patient. A region-of-interest analysis and calculating correlations between any pair of two brain regions, obtaining a connectivity matrix, will be done.
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) The Eating Disorders Examination Questionnaire (EDE-Q) is the self-report version of the Eating Disorder Examination (EDE). The 22 items on the four subscales of restraint, eating concern, weight concern, and shape concern are used to assess eating disorder-specific characteristics in their current manifestations during the last 28 days. 7-point rating scales are used to assess frequencies from 0 (characteristic was not present) to 6 (characteristic was present every day or to an extreme degree). Six further, non-scale-forming items also measure the frequency of diagnostically relevant core behaviors over the last 28 days. The EDE-Q is evaluated by calculating subscale mean values for the Restraint, Eating Concern, Weight Concern and Shape Concern subscales and a total score. At Baseline, Post Treatment and intermediate measurements, the instruction of EDE-Q will be modified to refer to a shortened shortened observation time (last week).
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) Hyperkinesia will be assessed with only one item (item 42) from the Structured Inventory for Anorexic and Bulimic Eating Disorders (SIAB). This Inventory is used to record the entire spectrum of eating disorder symptoms. Item 42 assesses excessive physical exercise ranging from 0 (no physical exercise) to 4 (very frequent physical exercise).
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) The Exercise and Eating Disorders Questionnaire (EED) is a clinically derived, self-report questionnaire. 19 items are used to assess compulsive exercise among eating disorder patients. The 6-point rating scale is used to assess the frequencies (never, rare, sometimes, often, mostly, always) during the last 4 weeks. A higher total score indicates a stronger manifestation of compulsive exercises.
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) The Autism-Spectrum Quotient-short version (AQ-k) is a self-assessment tool for screening for autistic disorder. The 10 items represent autistic symptoms and a 4-point response scale is used to assess the agreement (complete agreement, agree more, rather disagree, complete disagreement) to those.
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) The WHO Quality of Life Questionnaire (WHOQOL-BREF) with 26 items is a short form of the WHOQOL-100 and is an instrument for recording subjective quality of life. Items 1, 2, 5, 6, 7, 10, 17, 19, 20, and 22 will be used, ranging from 1 (very dissatisfied/ no agreement) to 5 (very satisfied/fully agreement). A higher total score indicates a increased quality of life.
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) 10 items assessing hunger, repetitive thought of food, fear of weight gain, drive for activity, inner tension, feeling full, nausea, feeling fat, depressed mood and feeling tired on a 10-point response scale ranging from 1 (not pronounced symptom) to 10 (strongly pronounced symptom).
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) The Liebowitz Social Anxiety Scale is a clinician-administered assessment that measures the fear and avoidance associated with social anxiety. Item 2,3,4,5,8,10,11,12,15 and 19 will be rated on the response scale for avoidance behavior from 1 (never) to 4 (almost always). Higher scores indicating greater severity of social anxiety.
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) Anhedonia will be assessed with the german version of the Snaith-Hamilton Pleasure Scale (SHAPS-D) that assesses self-reported anhedonia in psychiatric patients. The respective degree of consent regarding the 14 items on the questionnaire will be rated on a bipolar four-point response scale. For the evaluation, each disagree response ('disagree' or 'strongly disagree') is given 1 point and each agree response is given 0 points. By adding up the points, a higher value indicates a greater degree of anhedonia.
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) Measured with leucocytes Giga per liter (G/l).
Hematology in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49) Measured with hematocrit liter per liter (l/l).
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) Measured with albumin grams per liter (g/l).
Trial Locations
- Locations (1)
Eating Disorder Unit, Clinic of Consultation-Liaison Psychiatry and Psychosomatic Medicine, University Hospital Zurich
🇨🇭Zurich, Switzerland