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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Metreleptin-assisted therapy | Experimental | 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 | Placebo Comparator | 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). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Metreleptin | Drug | 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 hydrogen (pH) 4.25. The resulting solution is administered by subcutaneous injection. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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. | 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 | Body weight status will be indicated by weight in kilograms (kg). | Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49) |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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. |
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Main key inclusion criteria:
Main key exclusion criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Gabriella Milos, Prof. Dr. med. | Contact | 0041 44 255 52 80 | Gabriella.Milos@usz.ch | |
| Lisa Guth, MSc Psychology | Contact | 0041 44 255 97 17 | Lisa.Guth@usz.ch |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Eating Disorder Unit, Clinic of Consultation-Liaison Psychiatry and Psychosomatic Medicine, University Hospital Zurich | Recruiting | Zurich | Canton of Zurich | 8091 | Switzerland |
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| ID | Term |
|---|---|
| D000856 | Anorexia Nervosa |
| D015430 | Weight Gain |
| D003863 | Depression |
| ID | Term |
|---|---|
| D001068 | Feeding and Eating Disorders |
| D001523 | Mental Disorders |
| D001836 | Body Weight Changes |
| D001835 | Body Weight |
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| ID | Term |
|---|---|
| C415771 | metreleptin |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
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Placebo-controlled, double-blind, randomized trial. The efficacy of Metreleptin in Anorexia Nervosa patients will be tested against an inactive Placebo.
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| Sodium chloride | Drug | 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. |
|
| 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 | 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. | 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 | 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). | 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 | 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). | 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 | 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. | 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 | 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. | 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 | 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. | 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 | 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). | 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 | 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. | 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 | 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. | 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 | Measured with hemoglobin grams per liter (g/l). | 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 | Measured with hematocrit liter per liter (l/l). | 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 | Measured with erythrocytes Tera per liter (T/l). | 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 | Measured with thrombocytes Giga per liter (G/l). | 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 | Measured with leucocytes Giga per liter (G/l). | 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 | Measured with Sodium millimoles per liter (mmol/l). | 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 | Measured with potassium millimoles per liter (mmol/l). | 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 | Measured with phosphate millimoles per liter (mmol/l). | 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 | Measured with creatinine micromoles per liter (µmol/l). | 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 | Measured with creatinine kinase Units per liter (U/l). | 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 | Measured with estimated Glomerular Filtration Rate (eGFR) milliliters per minute (ml/min). | 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 | Measured with bilirubin total micromoles per liter (µmol/l). | 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 | Measured with gamma-glutamyltranspeptidase Units per liter (U/l). | 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 | Measured with alanine aminotransferase Units per liter (U/l). | 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 | Measured with alkaline phosphatase Units per liter (U/l). | 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 | Measured with pancreatic amylase Units per liter (U/l). | 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 | Measured with lipase Units per liter (U/l). | 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 | Measured with C-reactive protein (CRP) milligrams per liter (mg/l). | 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 | Measured with calcium millimoles per liter (mmol/l). | 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 | Measured with chloride millimoles per liter (mmol/l). | 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 | Measured with aspartat-aminostransf. (GOT) Units per liter (U/l). | 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 | Measured with magnesium millimoles per liter (mmol/l). | 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 | Measured with protein grams per liter (g/l). | 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 | Measured with albumin grams per liter (g/l). | 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 | Measured with thyroid-stimulating hormon (TSH) milliunits per liter (mU/l). | 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 | Measured with free thyroxin (fT3) picomole per liter (pmol/l). | 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 | Measured with free thyroxin (fT4) picomole per liter (pmol/l). | 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 | Measured with follicle stimulating hormone (FSH) international units per liter (IE/l). | 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 | Measured with luteinizing hormone (LH) international units per liter (IE/l). | 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 | Measured with morning cortisol level nanomoles per liter (nmol/l). | 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 | Measured with fasting insulin millimoles per liter (pmol/l). | 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 | Measured with leptin nanogram per milliliter (ng/ml). | 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 | Measured with ghrelin picogram per milliliter (pg/ml). | 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 | Measured with brain derived neurotrophic factor (BDNF) picogram per milliliter (pg/ml). | 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 | Measured with cytokine (IL-6) picogram per milliliter (pg/ml). | 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 | Measured with cytokine (IL-7) picogram per milliliter (pg/ml). | 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 | Measured with estradiol picomole per liter (pmol/l). | 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 | Measured with testosteron nanomoles per liter (nmol/l). | 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 | Measured with free testosteron picomole per liter (pmol/l). | 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 | Measured with progesteron nanomoles per liter (nmol/l). | 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 | Measured with C-peptide nanomoles per liter (nmol/l). | 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 | Measured with prolactin microgram per liter (µg/l). | 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 | Measured with IGF-1 microgram per liter (µg/l). | 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 | Measured with orexin picogram per milliliter (pg/ml). | 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 | Measured with oxytocin (unit TBD). | 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 | Measured with apodinectin (unit TBD). | 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 | Measured with NF-L (unit TBD). | 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 | Measured with GFAP (unit TBD). | 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 | Measured with leptin receptor (unit TBD). | 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 | Measured with TNF-Alpha (unit TBD). | 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 | Assessed with ECG and will be analysed with the software HRVTool in Matlab. | 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 | Measured with Glucose millimoles per liter (mmol/l). | Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49) |
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| D012816 |
| Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
| D017670 |
| Sodium Compounds |