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Dynamics of Leptin and Endocrine Function

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00001543
First Posted: November 4, 1999
Last Update Posted: March 4, 2008
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by:
National Institutes of Health Clinical Center (CC)
  Purpose

This is a study investigating the hormones and substances important to the stress response. The hormone that is most directly responsible for stress response is called corticotropin-releasing hormone (CRH). CRH is produced in the hypothalamus of the brain and causes the pituitary gland to produce another hormone called ACTH. The hormone ACTH then acts on the adrenal glands causing them to produce the hormone cortisol.

Unfortunately, CRH levels are unable to be measured in simple blood samples. However, substances like cortisol and leptin can provide information as to the activity of the hypothalamus.

The hormone leptin is associated with the regulation of body weight and the normal maintenance of bodily functions (homeostasis). It is found in fat cell (adipocyes) and communicates the nutritional status of the body to the brain (central nervous system). Research using animals has shown that defects in the communication between leptin and the brain causes obesity (the state of being overweight). It has also been noted that obese humans tend to have high levels of leptin.

By studying patients with abnormal genes responsible for leptin production, researchers have found that a least one leptin gene must be intact for the normal secretion of hormones to proceed. These results show that the hormone leptin is produced outside of the brain in fat cells and acts directly on the function of the hypothalamus within the brain. Researchers believe that leptin plays a key role in the normal release of hormones from the HPA axis.

Researchers intend on continuing to study the role of leptin in fat distribution, and the activity of the HPA axis in normal volunteers. In addition, this study will focus on the role of leptin in depression, because depression is characterized by changes in food intake, body weight, and neuroendocrine function. Data gathered from this study will provide a better understanding of the causes and medical consequences of major depression.


Condition
Healthy Involutional Depression

Study Type: Observational
Official Title: Dynamics of Leptin and Endocrine Function

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 230
Study Start Date: March 1996
Estimated Study Completion Date: June 2002
Detailed Description:
Our group has tested the hypothesis that the molecules involved in the neurobiology of the stress response are key elements in the pathophysiology, treatment, and medical consequences of major depressive disorder. Leptin is implicated in the regulation of adipose tissue, body weight and homeostasis. In the first three years of this protocol we accomplished the following: (1) discovered leptin pulsatility; (2) showed that is secreted in a highly organized manner in men and women; (3) showed for the first time in humans an inverse relation between rapid fluctuations in plasma leptin concentrations in healthy volunteers and those of adrenocorticotropic hormone (ACTH) and cortisol; (4) demonstrated a complex relation between the minute-to-minute dynamics of leptin and those of luteinizing hormone and estradiol; (5) showed a striking correlation between the 24-h dynamics of leptin and those of TSH and GH; (6) demonstrated highly significant correlation between hourly fluctuations of leptin levels and those of psychometric variables such as sadness, social withdrawal, and carbohydrate craving, and (7) showed that women produce twice as much leptin per secretory event than men. By studying patients with a leptin gene mutation we showed that at least one intact copy of the leptin gene is required for the regulation of TSH function and GH architecture in humans. These results indicate that leptin, a peripherally secreted molecule, appears to modulate the secretion of hypothalamic hormones. We have therefore proposed that hypothalamic neuroendocrine transduction, a key function of the CNS, may be regulated by leptin, a peripheral pulsatile signal of nutritional status. We would like to continue and expand our studies on the interactions of leptin, fat distribution, and the pituitary-adrenal axis in normal volunteers and also in patients with depression, because depression is characterized by alterations in food intake, body weight, and neuroendocrine function. Leptin profoundly affects the regulation of these three parameters. Leptin also increases insulin resistance, being therefore a risk factor for coronary artery disease, which is more prevalent and associated with higher mortality in depressed patients than in the general population. The data to be generated by this study will provide a better understanding of pathophysiology and medical consequences of major depression.
  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Depressed patients must have a history of past major depression of at least four months duration, or a history of two or more briefer episodes. Must be overweight.

Must not need a hospital admission as part of their treatment.

Overweight normal volunteers.

No subjects on chronic medication which cannot be washed out for one month.

No subjects with any serious medical illness.

No women who are pregnant, trying to become pregnant, or sexually active and not using effective contraception.

No patients with HIV infection.

No subjects who cannot discontinue use of alcohol/tobacco.

  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00001543


Locations
United States, Maryland
National Institute of Mental Health (NIMH)
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Institute of Mental Health (NIMH)
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00001543     History of Changes
Other Study ID Numbers: 960048
96-M-0048
First Submitted: November 3, 1999
First Posted: November 4, 1999
Last Update Posted: March 4, 2008
Last Verified: June 2002

Keywords provided by National Institutes of Health Clinical Center (CC):
Major Depression
Metabolic Clearance Rate
Pulsatility
Adrenocorticotropic Hormone
Cortisol
Corticotropin Releasing Hormone Binding Protein
Pharmacokinetics
Half-Life
Bioavailability
Cushing's Syndrome

Additional relevant MeSH terms:
Depression
Depressive Disorder, Major
Behavioral Symptoms
Depressive Disorder
Mood Disorders
Mental Disorders
Corticotropin-Releasing Hormone
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs