Study of Leptin for the Treatment of Hypothalamic Amenorrhea

• Status: Completed
• Trial end date: 2016-12-01
• Target enrollment: 0
• Participant gender: Female

Summary

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 (exercise-induced) amenorrhea (HA) who are being treated with oral contraceptive pills (OCPs), 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 (exercise-induced) amenorrhea may be the reason for the lack of menstrual cycles, hormone abnormalities, and bone loss associated with this condition.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Beth Israel Deaconess Medical Center
• Collaborators: Amgen; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Center for Research Resources (NCRR); National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Treatments: Contraceptive Agents; Contraceptives, Oral; Contraceptives, Oral, Combined

Criteria

Inclusion criteria for HA subjects

• Hypothalamic amenorrhea of at least 6 months duration with low or normal LH and FSH, e.g. due to strenuous exercise (running >20 miles per week or equivalent) or low weight

• Can be secondary HA OR primary HA with some pubertal development and normal screening labs

• Age 18-35 years old

• Body weight within +/- 15% of ideal body weight and stable for 6 months (no change > 5 lbs)

• Baseline leptin <5 ng/mL (except for the Cognitive Sub-Study Baseline visit where baseline leptin will be greater than 5ng/mL)

Inclusion criteria for eumenorrheic controls for Reward Sub-study

• Normal menstrual cycles (between 25 and 35 days)

• Age 18-35

• Body weight within +/- 15% of ideal body weight and stable 6 months (no change > 5 lbs)

• Baseline leptin >5 ng/mL

Exclusion criteria:

• We will exclude subjects with:

• Significant medical history that may affect the concentrations of the hormones to studied or ability to participate in the study

• renal or hepatic disease (creatinine > 1.4, AST/ALT > 2x upper limit of normal)

• 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 (Hb10 gm/dL on 2 occasions)

• Conditions that are contraindicated for oral contraceptive use:

• Thrombophlebitis or thromboembolic disorders

• A past history of deep vein thrombophlebitis or thromboembolic disorders

• Cerebral vascular or coronary artery disease

• Known or suspected carcinoma of the breast

• Carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasia

• Undiagnosed abnormal genital bleeding

• Hepatic adenomas or carcinomas

• Cholestatic jaundice of pregnancy or jaundice with prior OCP use

• Other endocrine causes of amenorrhea, e.g.

• hyperprolactinemia

• hypothyroidism or hyperthyroidism

• Cushing's syndrome

• congenital adrenal hyperplasia (elevated 17 OH progesterone)

• polycystic ovarian syndrome (elevated androgens or LH/FSH ratio >1.5)

• primary ovarian failure (elevated FSH)

• On medications known to affect the hormones to be measured such as

• glucocorticoids

• anti seizure medications

• thyroid hormones

• estrogen (must be off at least 3 months prior to participating in the study)

• A known history of anaphylaxis or anaphylactoid-like reactions, or a known hypersensitivity to E. Coli derived proteins

• Breast feeding, pregnant, or wanting to become pregnant during the next 6 months.

• We will screen for these conditions through a detailed history and systems review, physical examination, laboratory evaluation (as described above in Screening Methods), and EKG.

• In the Reward Sub-study subjects will be asked to fill out a standard BIDMC MRI safety screening form prior to entering the magnet.