Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04063488 |
| Other study ID # |
00209730 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
June 20, 2019 |
| Est. completion date |
August 13, 2021 |
Study information
| Verified date |
December 2021 |
| Source |
Northwestern University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial 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.
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.
