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

NCT01422733 | Withdrawn Early Phase 1 FDA Drug

• 1 other identifier: CBS004
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Changes in free testosterone or 17-hydroxyprogesterone levels after ACTH and rhCG administration respectively, before and after hydrocortisone administration for 12 weeks

  12 weeks after hydrocortisone administration

Secondary Outcomes (2)

• Changes in adrenal and ovarian steroid precursors after ACTH and rhCG; body composition via air displacement plethysmography, BMI, and glucose tolerance testing results; baseline and after 12 weeks of hydrocortisone administration

  12 weeks after hydrocortisone administration

• Morning cortisol

  72 hours following discontinuation of hydrocortisone

Study Arms (1)

hydrocortisone, dexamethasone, Cosyntropin (ACTH), rhCG

EXPERIMENTAL

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

Drug: Hydrocortisone; Drug: dexamethasone; Drug: Cosyntropin; Drug: rhCG

Interventions

Hydrocortisone DRUG

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

hydrocortisone, dexamethasone, Cosyntropin (ACTH), rhCG

dexamethasone DRUG

1 mg PO twice

hydrocortisone, dexamethasone, Cosyntropin (ACTH), rhCG

Cosyntropin DRUG

250 micrograms IV twice

Also known as: Tetracosactide

hydrocortisone, dexamethasone, Cosyntropin (ACTH), rhCG

rhCG DRUG

25 mcg IV twice

Also known as: (Ovidrel)

hydrocortisone, dexamethasone, Cosyntropin (ACTH), rhCG

Eligibility Criteria

• Age: 7 Years - 16 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Virginia: lead

Study Sites (1)

University of Virginia Center for Research in Reproduction

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Conditions

Obesity; Polycystic Ovary Syndrome

Interventions

Hydrocortisone; Dexamethasone; Cosyntropin; Ovidrel

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids; Pregnadienetriols; Pregnadienes; Steroids, Fluorinated; Adrenocorticotropic Hormone; Melanocortins; Pro-Opiomelanocortin; Hypothalamic Hormones; Peptide Hormones; Pituitary Hormones, Anterior; Pituitary Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Nerve Tissue Proteins; Proteins

Study Officials

• Christine Burt Solorzano, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Pediatrics

Study Record Dates

• First Submitted: August 22, 2011
• First Posted: August 24, 2011
• Study Start: June 1, 2018
• Primary Completion: July 17, 2018
• Study Completion: July 17, 2018
• Last Updated: July 19, 2018

Record last verified: 2018-07

Locations

US (1)