Study of Leptin for the Treatment of Hypothalamic Amenorrhea - Full Text View

Sponsor:	Beth Israel Deaconess Medical Center
Collaborators:	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) National Center for Research Resources (NCRR) Amgen
Information provided by:	Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier:	NCT00130117

Purpose

The purpose of this study is to determine whether administration of an investigational medication called leptin (r-metHuLeptin) in replacement doses can improve bone health, reproductive function, hormone levels, immune function, and overall sense of well-being in women with hypothalamic amenorrhea, compared to placebo. Women with hypothalamic amenorrhea have low leptin levels. This study is based on the hypothesis that the relative leptin deficiency in women with hypothalamic amenorrhea may be the reason for the lack of menstrual cycles, hormone abnormalities, and bone loss associated with this condition.

Condition	Intervention	Phase
Amenorrhea	Drug: r-metHuLeptin	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Randomized, Double-blind, Placebo-controlled Trial of Human Recombinant Leptin (r-metHuLeptin) for the Treatment of Hypothalamic Amenorrhea

Resource links provided by NLM:

MedlinePlus related topics: Menstruation

Drug Information available for: Leptin Metreleptin

U.S. FDA Resources

Further study details as provided by Beth Israel Deaconess Medical Center:

Primary Outcome Measures:

the difference between the placebo and leptin treated groups in the change in bone mineral density (BMD) at the anteroposterior (AP) spine from baseline to 36 weeks [ Time Frame: 36 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

evidence of ovulation based on menstrual bleeding and progesterone levels [ Time Frame: 36 weeks ] [ Designated as safety issue: No ]
hormone levels and bone markers [ Time Frame: 36 weeks ] [ Designated as safety issue: Yes ]
immune function [ Time Frame: 36 weeks ] [ Designated as safety issue: Yes ]
body composition (weight and body fat) [ Time Frame: 36 weeks ] [ Designated as safety issue: No ]
total, radial, hip bone density [ Time Frame: 36 weeks ] [ Designated as safety issue: Yes ]
resting metabolic rate [ Time Frame: 36 weeks ] [ Designated as safety issue: No ]
overall sense of well-being, appetite and food intake [ Time Frame: 36 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	34
Study Start Date:	August 2005
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Detailed Description:

Leptin is a hormone secreted by fat cells under normal conditions and acts in the brain to regulate energy usage and hormone levels. Women with hypothalamic amenorrhea who do not have regular periods have low leptin levels and may also have other hormone abnormalities as well as loss of bone density (osteopenia or osteoporosis). This study will evaluate how leptin (a fat cell hormone that normally circulates in the blood) affects bone density, menstrual periods, hormone levels, bone metabolism (how bone forms and turns over), immune function (how well the body can fight infection), metabolic rate (how many calories are used at rest), and overall sense of well-being and appetite in women with hypothalamic amenorrhea (i.e. no regular menstrual periods due to low levels of pituitary hormones that regulate estrogen production from the ovary).

Comparison: leptin-treated group to placebo-treated group

Eligibility

Ages Eligible for Study:	18 Years to 35 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Hypothalamic amenorrhea of at least 6 months duration with low or normal leutinizing hormone (LH) and follicle stimulating hormone (FSH), e.g. due to strenuous exercise (running >20 miles per week or equivalent) or low weight
Age 18-35 years old
Body weight within +/- 15% of ideal body weight and stable ≥ 6 months (no change > 5 lbs)
Baseline leptin level < 4 ng/mL

Exclusion Criteria:

Significant medical history that may affect the concentrations of the hormones to be studied or the ability to participate in the study (renal or hepatic disease, diagnosed diabetes mellitus, myocardial ischemia, malignancy other than basal cell carcinoma of the skin or in situ carcinoma of the cervix, malabsorption, alcoholism, drug abuse, or smoking, active eating disorder, depression or other psychiatric disease, anemia)
Other endocrine causes of amenorrhea (hyperprolactinemia, hypothyroidism or hyperthyroidism, Cushing's syndrome, congenital adrenal hyperplasia, polycystic ovarian syndrome, primary ovarian failure)
On medications known to affect the hormones to be measured (glucocorticoids, anti-seizure medications, thyroid hormones, estrogen)
Breast feeding, pregnant, or wanting to become pregnant during the next 6 months

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00130117

Locations

United States, Massachusetts
Beth Israel Deaconess Medical Center General Clinical Research Center
Boston, Massachusetts, United States, 02215

Sponsors and Collaborators

Beth Israel Deaconess Medical Center

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

National Center for Research Resources (NCRR)

Amgen

Investigators

Principal Investigator:	Christos S Mantzoros, MD, DSc	Beth Israel Deaconess Medical Center, Harvard Medical School
Study Director:	Chuanyun Gao, MD	Beth Israel Deaconess Medical Center, Harvard Medical School

More Information

Additional Information:

Click here for more information about the Mantzoros Research Group. This link exits the ClinicalTrials.gov site

Click here for more information about Beth Israel Deaconess Medical Center. This link exits the ClinicalTrials.gov site

Publications:

Welt CK, Chan JL, Bullen J, Murphy R, Smith P, DePaoli AM, Karalis A, Mantzoros CS. Recombinant human leptin in women with hypothalamic amenorrhea. N Engl J Med. 2004 Sep 2;351(10):987-97.

Chan JL, Mantzoros CS. Role of leptin in energy-deprivation states: normal human physiology and clinical implications for hypothalamic amenorrhoea and anorexia nervosa. Lancet. 2005 Jul 2-8;366(9479):74-85. Review.

Responsible Party:	Beth Israel Deaconess Medical Center ( Christos Mantzoros )
Study ID Numbers:	2004P-000123
Study First Received:	August 11, 2005
Last Updated:	August 28, 2009
ClinicalTrials.gov Identifier:	NCT00130117 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Beth Israel Deaconess Medical Center:

leptin
hypothalamic amenorrhea
neuroendocrine function
bone metabolism

Additional relevant MeSH terms:

Pathologic Processes
Menstruation Disturbances
Amenorrhea

ClinicalTrials.gov processed this record on February 08, 2010