Effect of Spironolactone on Adrenal or Ovarian Androgen Production in Overweight Pubertal Girls With Androgen Excess

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2012 by University of Virginia.
Recruitment status was  Not yet recruiting
Sponsor:
Information provided by (Responsible Party):
Christine Burt Solorzano, University of Virginia
ClinicalTrials.gov Identifier:
NCT01422759
First received: August 22, 2011
Last updated: June 12, 2012
Last verified: June 2012
  Purpose

This study will test whether spironolactone administration can ameliorate androgen (male hormone) overproduction in overweight pubertal girls with androgen excess. The investigators hypothesize that reduction in P450c17alpha overactivity and androgen receptor blockade by 12 weeks of spironolactone administration will improve androgen levels after adrenal stimulation testing with ACTH and ovarian stimulation testing with recombinant human chorionic gonadotropin (r-hCG).


Condition Intervention
Obesity
Hyperandrogenemia
Polycystic Ovary Syndrome
Drug: Spironolactone
Drug: Dexamethasone
Drug: Cosyntropin
Drug: r-hCG (Ovidrel)

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Effect of Spironolactone on Adrenal or Ovarian Androgen Production in Overweight Pubertal Girls With Androgen Excess (CBS006)

Resource links provided by NLM:


Further study details as provided by University of Virginia:

Primary Outcome Measures:
  • Changes in free testosterone and 17 OH progesterone levels after ACTH and r-hCG administration respectively, before and after spironolactone administration for 12 weeks [ Time Frame: 12 weeks after spironolactone treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Changes in adrenal and ovarian steroid precursors after ACTH and r-hCG; body composition via air displacement plethysmography, BMI, and glucose tolerance testing results; baseline and after 12 weeks of spironolactone administration [ Time Frame: 12 weeks after spironolactone administration ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Arms Assigned Interventions
Experimental: spironolactone, dexamethasone, Cosyntropin (ACTH), and r-hCG
12 weeks spironolactone, Dexamethasone and ACTH to perform standardized adrenal stimulation testing, dexamethasone and r-hCG to perform standardized ovarian stimulation testing
Drug: Spironolactone
50-100 mg PO BID (X 12 weeks)
Drug: Dexamethasone
1 mg PO twice
Drug: Cosyntropin
250 micrograms IV twice
Drug: r-hCG (Ovidrel)
25 mcg IV twice

  Eligibility

Ages Eligible for Study:   7 Years to 18 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • overweight(>85th BMI%) females
  • Early to late puberty (expected age range 7-18)
  • 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 LH, lipids, testosterone, prolactin, DHEAS, E2, glucose, and insulin and decreased FSH and/or SHBG

Exclusion Criteria:

  • Age < 7 or > 18 years
  • 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.
  • Abnormal laboratory studies will be confirmed by repeat testing to exclude laboratory error.
  • Morning cortisol < 3 µg/dL or history of Cushing syndrome or adrenal insufficiency
  • History of congenital adrenal hyperplasia or 17-hydroxyprogesterone > 300 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 >300 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 PCOS and adolescent 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 CRC 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01422759

Contacts
Contact: Michelle Y. Abshire, PhD 434-243-6911 pcos@virginia.edu
Contact: Christine Burt Solorzano, MD 434-243-6911 pcos@virginia.edu

Locations
United States, Virginia
University of Virginia Center for Research in Reproduction Not yet recruiting
Charlottesville, Virginia, United States, 22908
Contact: Michelle Y. Abshire, PhD    434-243-6911    pcos@virginia.edu   
Principal Investigator: Christine Burt Solorzano, MD         
Sub-Investigator: John C. Marshall, MD, PhD         
Sponsors and Collaborators
University of Virginia
Investigators
Principal Investigator: Christine Burt Solorzano, MD University of Virginia
  More Information

No publications provided

Responsible Party: Christine Burt Solorzano, Assistant Professor of Pediatrics, University of Virginia
ClinicalTrials.gov Identifier: NCT01422759     History of Changes
Other Study ID Numbers: CBS006, CBS006
Study First Received: August 22, 2011
Last Updated: June 12, 2012
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Obesity
Polycystic Ovary Syndrome
Overweight
Overnutrition
Nutrition Disorders
Body Weight
Signs and Symptoms
Ovarian Cysts
Cysts
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Gonadal Disorders
Endocrine System Diseases
Androgens
Cosyntropin
Dexamethasone
Dexamethasone 21-phosphate
Spironolactone
Dexamethasone acetate
BB 1101
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antiemetics
Autonomic Agents

ClinicalTrials.gov processed this record on July 20, 2014