The Effects of Metreleptin in Congenital Leptin Deficiency

2019-08-27 21:46:53 | BioPortfolio


This study has been designed to 1) provide access to metreleptin to the only two individuals in the US known to have congenital leptin deficiency (CLD) and 2) explore a variety of unanswered questions about leptin physiology in general and metreleptin therapy in CLD specifically.

The primary study endpoints include the following measures: body composition, measures of hepatic steatosis, measures of insulin sensitivity, and measures of sleep architecture.

Secondary study endpoints include assessment of clock gene expression, body temperature, thyroid function, gonadal function, cognitive function, eating behavior, physical activity, mood, quality of life, and body image.


Congenital leptin deficiency (CLD) is a rare autosomal recessive condition caused by a mutation in the leptin gene (LEP). This mutation leads to a severe deficiency in leptin, a hormone secreted primarily by adipocytes. Leptin is also secreted by gastric mucosal cells, in response to stimuli such as food intake. Leptin has many important physiologic roles, including serving as a signal to the hypothalamus of both long-term (adipocyte) and short-term (gastric) energy storage. Individuals with CLD have hyperphagia and morbid obesity with an onset in early childhood. Hypogonadotropic hypogonadism, insulin resistance, and immune dysfunction are also often observed in patients with CLD but these features can be of varying degrees of severity.

Recombinant human leptin (metreleptin; Myalept®) was approved by the U.S. Food and Drug Administration in 2014 to treat the complications of leptin deficiency in patients with generalized lipodystrophy (GL). Commercial use of metreleptin is restricted to patients with leptin deficiency due to GL. However, ~3 dozen patients worldwide who are known to have congenital leptin deficiency (CLD) have been treated safely and successfully with metreleptin in the investigational setting for two decades. Metreleptin therapy has been shown to reduce hunger and desire to eat in leptin-deficient humans, and significant weight loss is typical.

Some questions remain regarding the pluripotent effects of metreleptin in patients with CLD. Understudied aspects of physiology in these patients include the role of leptin (independent of weight) in insulin sensitivity, hepatic steatosis, and sleep. For each of these areas, there is preliminary evidence from humans or the ob/ob (leptin-deficient) mouse model for a beneficial role of leptin, but important knowledge gaps remain.

Study Design


Congenital Leptin Deficiency (Disorder)




Northwestern University Feinberg School of Medicine
United States


Enrolling by invitation


Northwestern University

Results (where available)

View Results


Published on BioPortfolio: 2019-08-27T21:46:53-0400

Clinical Trials [1762 Associated Clinical Trials listed on BioPortfolio]

Immunogenicity of Metreleptin in Patients With Generalized Lipodystrophy

MYALEPT™ (metreleptin) has been approved as an adjunct to diet as replacement therapy to treat the complications of leptin deficiency in patients with congenital or acquired generalized ...

Expanded Access Metreleptin Study

Metreleptin was approved in the United States as adjunct to diet as replacement therapy to treat the complications of leptin deficiency in patients with congenital or acquired generalized ...

A Pilot Study of the Functional Magnetic Resonance Imaging (fMRI) Response to Leptin and Pramlintide

The purpose of this study is to identify how certain parts of the brain that help control body weight respond to an infusion of hormones called leptin and amylin.

An Open-Label Treatment Protocol to Provide Metreleptin for the Treatment of Diabetes Mellitus and/or Hypertriglyceridemia Associated With Lipodystrophy

This is an open-label study to provide metreleptin for the treatment of diabetes mellitus and/or hypertriglyceridemia associated with lipodystrophy. This study intends to provide guidance ...

Use of rFXIII in Treatment of Congenital FXIII Deficiency, a Prospective Multi-centre Observational Study

This study is conducted globally. The aim of this observational study is to investigate the incidence of specific adverse drug reactions associated with the use of recombinant factor XIII ...

PubMed Articles [7695 Associated PubMed Articles listed on BioPortfolio]

Leptin Is Not Essential for Obesity-Associated Hypertension.

Hyperleptinemia is supposed to play a causal role in the development of obesity-associated hypertension, possibly via increased sympathetic tone. Hence patients with congenital leptin deficiency shoul...

Leptin receptor deficiency: a systematic literature review and prevalence estimation based on population genetics.

Leptin receptor (LepR) deficiency is an autosomal-recessive endocrine disorder causing early-onset severe obesity, hyperphagia and pituitary hormone deficiencies. As effective pharmacological treatmen...

Ratio of plasma BDNF to leptin levels are associated with treatment response in major depressive disorder but not in panic disorder: A 12-week follow-up study.

A link between brain-derived neurotrophic factor (BDNF) expression and the mood regulatory effect of leptin has been suggested in the pathophysiology of major depressive disorder (MDD). We investigate...

OSTα deficiency: A disorder with cholestasis, liver fibrosis and congenital diarrhea.

SLC51A encodes the alpha subunit of the heteromeric organic solute transporter alpha-beta (OSTα-OSTβ), an important contributor to intestinal bile acid (BA) reabsorption in the enterohepatic circula...

Leptin promotes epithelial-mesenchymal transition in benign prostatic hyperplasia through downregulation of BAMBI.

Benign prostatic hyperplasia (BPH) is a common disease in older men, and there is evidence that obesity is a causal factor. It is currently unclear whether the hormone leptin, which is positively corr...

Medical and Biotech [MESH] Definitions

Cell surface receptors for obesity factor (LEPTIN), a hormone secreted by the WHITE ADIPOCYTES. Upon leptin-receptor interaction, the signal is mediated through the JAK2/STAT3 pathway to regulate food intake, energy balance and fat storage.

A 16-kDa peptide hormone secreted from WHITE ADIPOCYTES. Leptin serves as a feedback signal from fat cells to the CENTRAL NERVOUS SYSTEM in regulation of food intake, energy balance, and fat storage.

An autosomal recessive disorder of CHOLESTEROL metabolism. It is caused by a deficiency of 7-dehydrocholesterol reductase, the enzyme that converts 7-dehydrocholesterol to cholesterol, leading to an abnormally low plasma cholesterol. This syndrome is characterized by multiple CONGENITAL ABNORMALITIES, growth deficiency, and MENTAL RETARDATION.

Any one of a group of congenital hemolytic anemias in which there is no abnormal hemoglobin or spherocytosis and in which there is a defect of glycolysis in the erythrocyte. In some cases, pyruvate kinase deficiency has been demonstrated; in other cases, glucose-6-phosphate dehydrogenase deficiency has been demonstrated.

An inherited metabolic disorder characterized by the intralysosomal accumulation of sulfur-containing lipids (sulfatides) and MUCOPOLYSACCHARIDES. Excess levels of both substrates are present in urine. This is a disorder of multiple sulfatase (arylsulfatases A, B, and C) deficiency which is caused by the mutation of sulfatase-modifying factor-1. Neurological deterioration is rapid.

More From BioPortfolio on "The Effects of Metreleptin in Congenital Leptin Deficiency"

Quick Search

Relevant Topics

Congenital Diseases
Congenital conditions are those which are present from birth. They include structural deformities or loss of function in organs such as the <!--LGfEGNT2Lhm-->heart, gut or skeletal system. They can be corrected by <!--LGfEGNT2Lhm-->surgery, m...

Hepatology is the study of liver, gallbladder, biliary tree, and pancreas, and diseases associated with them. This includes viral hepatitis, alcohol damage, cirrhosis and cancer. As modern lifestyles change, with alcoholism and cancer becoming more promi...

Endocrine Disorders
Endocrine disorders are grouped into two categories: hormone imbalance - when a gland produces too much or too little of an endocrine hormone development of lesions (such as nodules or tumors) in the endocrine system, which may or may not affect...

Searches Linking to this Trial