Clinical trial NCT04063488: The Effects of Metreleptin in Congenital Leptin Deficiency
Official title: An Observational Study of the Effects of Metreleptin in Young Adults With Congenital Leptin Deficiency
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Congenital Leptin Deficiency (Disorder)
Lead sponsor: Northwestern University
Sponsor class: OTHER
First posted: 2019-08-21
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study will enroll two young adults who have been recently diagnosed with congenital leptin deficiency (homozygous for the pathogenic variant c.398delG in exon 3 of the leptin gene). They have not been previously treated with metreleptin.

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of congenital leptin deficiency
* Age 18 years or older
* Must agree to use contraception for the duration of treatment with metreleptin and for 6 months post-treatment completion.

Exclusion Criteria:

* Presence of a clinically significant medical condition that could significantly affect the risk/benefit ratio for metreleptin treatment, as judged by the PI
* Known allergies to E. coli-derived proteins or hypersensitivity to any component of metreleptin treatment

Primary outcomes:
measure: change in hepatic steatosis
timeFrame: repeated measures at baseline, 1 week, 1 month, 3 months, 6 months, 12 months, 18 months, 24 months
measure: change in insulin sensitivity
timeFrame: repeated measures at baseline, 1 week, 3 months
measure: change in sleep architecture
timeFrame: repeated measures at baseline, 3 months, 6 months, 12 months
measure: change in body composition
timeFrame: repeatured measures at baseline, 3 months, 6 months, 12 months, 18 months, 24 months
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
Study officials:
affiliation: Dr.
name: Lisa Neff, MD
role: PRINCIPAL_INVESTIGATOR
References: