Effect of Longer-term Adrenal Suppression Using Low Dose Hydrocortisone on Androgen Overproduction

NCT ID: NCT01422733

Last Updated: 2018-07-19

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: EARLY_PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-06-01
• Study Completion Date: 2018-07-17

Brief Summary

This study will test whether longer-term suppression of adrenal function can ameliorate androgen (male hormone) overproduction in overweight early pubertal girls with androgen excess. The investigators hypothesize that suppression of nighttime adrenocorticotropin hormone (ACTH) production by 12 weeks of evening oral hydrocortisone administration will improve androgen levels in girls with adrenal androgen overproduction. Specifically, this intervention will improve androgen levels after adrenal stimulation testing with ACTH or ovarian stimulation testing with recombinant human chorionic gonadotropin (rhCG).

Conditions

Hyperandrogenemia; Obesity; Polycystic Ovary Syndrome

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

hydrocortisone, dexamethasone, Cosyntropin (ACTH), rhCG

12 weeks hydrocortisone, dexamethasone, and Cosyntropin (ACTH) to perform standardized adrenal stimulation testing; dexamethasone, and rhCG to perform standardized ovarian stimulation testing

Group Type: EXPERIMENTAL

Hydrocortisone

Intervention Type: DRUG

10mg/m2/per day PO at bedtime (X12 weeks)

dexamethasone

Intervention Type: DRUG

1 mg PO twice

Cosyntropin

Intervention Type: DRUG

250 micrograms IV twice

rhCG

Intervention Type: DRUG

25 mcg IV twice

Interventions

Hydrocortisone

10mg/m2/per day PO at bedtime (X12 weeks)

Intervention Type: DRUG

dexamethasone

1 mg PO twice

Intervention Type: DRUG

Cosyntropin

250 micrograms IV twice

Intervention Type: DRUG

rhCG

25 mcg IV twice

Intervention Type: DRUG

Other Intervention Names

Tetracosactide; (Ovidrel)

Eligibility Criteria

Inclusion Criteria

• Overweight(>85th BMI%) females
• Early puberty defined by Tanner 1-2 breast development (expected age range 7-16)
• Hyperandrogenemic (free testosterone greater than 2.5 standard deviations above the mean for normal control subjects of the same Tanner Stage)
• Screening labs within age-appropriate normal range, with the exception of a mildly low hematocrit (see below) and the hormonal abnormalities inherent in obesity which could include mildly elevated luteinizing hormone (LH), lipids, testosterone, prolactin, DHEAS, E2, glucose, and insulin; and decreased follicle-stimulating hormone (FSH) and/or sex hormone-binding globulin (SHBG)

Exclusion Criteria

• Age < 7 or > 16 y
• Inability to comprehend what will be done during the study or why it will be done
• BMI-for-age < 5th percentile
• Positive pregnancy test or lactation.
• Screening labs outside of age-appropriate normal range (Abnormal laboratory studies will be confirmed by repeat testing to exclude laboratory error)
• Morning cortisol < 5 µg/dL or history of Cushing syndrome or adrenal insufficiency
• History of congenital adrenal hyperplasia or 17-hydroxyprogesterone > 295 ng/dL, which suggests the possibility of congenital adrenal hyperplasia (if postmenarcheal, the 17-hydroxyprogesterone will be collected during the follicular phase, or ≥ 40 days since last menses if oligomenorrheic). NOTE: If a 17-hydroxyprogesterone >295 mg/dL is confirmed on repeat testing, an ACTH-stimulated 17-hydroxyprogesterone <1000 ng/dL will be required for study participation.
• Total testosterone > 150 ng/dL, which suggests the possibility of a virilizing neoplasm
• DHEAS greater than the upper limit of age-appropriate normal range (mild elevations may be seen in polycystic ovary syndrome (PCOS) and adolescent hyperandrogenemia (HA), and elevations < 1.5 times the age-appropriate upper limit of normal will be accepted in these groups)
• Virilization
• Previous diagnosis of diabetes, fasting glucose ≥126 mg/dL, or a hemoglobin A1c ≥6.5%
• Abnormal thyroid stimulating hormone (TSH) for age. Subjects with stable and adequately treated hypothyroidism, reflected by normal TSH values, will not be excluded.
• Abnormal prolactin. Mild elevations may be seen in overweight girls, and elevations <1.5 times the upper limit of normal will be accepted in this group.
• Persistent hematocrit <36% and hemoglobin <12 g/dL. Subjects with a mildly low hematocrit (33-36%) will be asked to take iron in the form of ferrous gluconate for up to 60 days. Subjects weighing ≤ 36 kg will take one 300-325 mg tablet oral ferrous gluconate daily (containing 36 mg elemental iron);subjects weighing >36 kg will take two 300-325 mg tablets oral ferrous gluconate daily (containing 36 mg elemental iron each). They will return to the Clinical Research Unit (CRU) after 30-60 days of iron therapy to have their hemoglobin or hematocrit rechecked and will proceed with the remainder of the study if it is ≥12 g/dL or ≥36%, respectively.
• Persistent liver test abnormalities, with the exception that mild bilirubin elevations will be accepted in the setting of known Gilbert's syndrome. Mild elevations may be seen in overweight girls, so elevations <1.5 times the upper limit of normal will be accepted in this group.
• Significant history of cardiac or pulmonary dysfunction (e.g., known or suspected congestive heart failure; asthma requiring intermittent systemic corticosteroids; etc.)
• Abnormal sodium, potassium, or bicarbonate concentrations, or elevated creatinine concentration (confirmed on repeat)
• No medications known to affect the reproductive system or glucose metabolism can be taken in the 3 months prior to the study. Such medications include oral contraceptive pills, progestins, metformin, glucocorticoids, and psychotropics.

• Minimum Eligible Age: 7 Years
• Maximum Eligible Age: 16 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University of Virginia

OTHER

Sponsor Role: lead

Responsible Party

Christine Burt Solorzano

Assistant Professor of Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Christine Burt Solorzano, MD

Role: PRINCIPAL_INVESTIGATOR

University of Virginia

Locations

University of Virginia Center for Research in Reproduction

Charlottesville, Virginia, United States

Countries

United States

Other Identifiers

CBS004

Identifier Type: OTHER

Identifier Source: secondary_id

CBS004

Identifier Type: -

Identifier Source: org_study_id