Metreleptin in Anorexia Nervosa (METRAN)

Gabriella Milos

Status and phase: Enrolling; Phase 2

Conditions: Anorexia Nervosa

Treatments: Drug: Sodium chloride; Drug: Metreleptin

Study type: Interventional

Funder types: Other

Identifiers

NCT06305182

BASEC 2022-01328

Details and patient eligibility

About

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.

Full 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.

Enrollment: 50 estimated patients

Sex: All

Ages: 18 to 40 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Current diagnosis of AN according to fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnosed with Structured Clinical Interview for DSM-5 (SCID-5)
• BMI > 13 kg/m2; BMI ≤ 17.5 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: 18 - 40 years
• Depressive symptoms: HAMD-17 ≥ 8
• Negative pregnancy test, non-lactating and double birth control
• Informed Consent as documented by signature

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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50 participants in 2 patient groups, including a placebo group

Metreleptin-assisted therapy

Experimental group

Description:

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.

Treatment:

Drug: Metreleptin

Placebo-therapy

Placebo Comparator group

Description:

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).

Treatment:

Drug: Sodium chloride