Metformin for the Treatment of Premature Pubarche in Girls

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Richard S. Legro, M.D., Milton S. Hershey Medical Center
ClinicalTrials.gov Identifier:
NCT01316042
First received: March 15, 2011
Last updated: June 17, 2013
Last verified: June 2013
  Purpose

The primary objective of this study is to determine the safety and efficacy of metformin in lowering serum DHEAS levels in girls with premature pubarche and secondary, to observe changes in hormones associated with pubertal development including gonadotropins, sex steroids, insulin, adipocytokines, and growth factors.


Condition Intervention
Premature Pubarche
Drug: sugar pill
Drug: Metformin, glucophage

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double Blind Randomized Controlled 12 Month Trial of Metformin for the Treatment of Premature Pubarche in Girls

Resource links provided by NLM:


Further study details as provided by Milton S. Hershey Medical Center:

Primary Outcome Measures:
  • Change in serum DHEAS levels [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • progression of puberty [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    progression of puberty as determined by change in hormones associated with pubertal development


Estimated Enrollment: 60
Study Start Date: May 2011
Estimated Study Completion Date: April 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: sugar pill
2 pills per day for 12 months
Drug: sugar pill
2 pills per day for 12 months
Active Comparator: Metformin
2 212.5mg pill/day for 12 months
Drug: Metformin, glucophage
2 212.5mg pills/day for 12 months
Other Name: metformin

  Eligibility

Ages Eligible for Study:   4 Years to 10 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Girls aged 4-10 with pubic hair prior to 8 years of age
  2. Elevated DHEAS level above age normal levels
  3. Informed consent from parents and assent from the girl

Exclusion Criteria:

  1. Diagnosis of incomplete precocious puberty, peripheral precocious puberty, or evidence of any abnormal pituitary, hypothalamic, adrenal, thyroid, and gonadal function other than premature secretion of adrenal androgens.
  2. Chronic illness requiring treatment that may interfere with growth and development, i.e. chronic steroid use, renal failure, etc.
  3. 21-hydroxylase deficiency or other enzyme deficiency leading to the phenotype of congenital adrenal hyperplasia. 21-hydroxylase deficiency will be excluded in all patients by a fasting 17-hydroxyprogesterone (17-OHP) level < 2 ng/mL. In the case of elevated fasting 17-OHP levels, an ACTH stimulation test will be performed. A 1-hour stimulated value > 10 ng/mL will be an exclusion 82. As 21 hydroxylase deficiency is a congenital condition, any normal level in the past of 17-hydroxyprogesterone allows entry into this study.
  4. Uncorrected thyroid disease (defined as TSH < 0.2 mIU/ML or > 5.5 mIU/mL). A normal level within the last year is adequate for entry.
  5. Type I or Type II diabetes (defined as a fasting serum glucose > 125mg/dL on two occasions 83), or patients receiving anti-diabetic medications such as insulin, thiazolidinediones, acarbose, or sulfonylureas; patients currently receiving metformin XR for a diagnosis of Type I or Type II diabetes or for PCOS are also specifically excluded.
  6. Liver disease defined as AST or ALT > 2 times normal or total bilirubin > 2.5 mg/dL.
  7. Renal disease defined as BUN > 30 mg/dL or serum creatinine > 1.4 mg/dL.
  8. Significant anemia (Hemoglobin < 10 mg/dL).
  9. History of deep venous thrombosis, pulmonary embolus, or cerebrovascular accident.
  10. Known heart disease (New York Heart Association Class II or higher).
  11. Enrolled simultaneously into other investigative studies that require medications, proscribe the study medications, or otherwise prevent compliance with the protocol. Patients who anticipate taking longer than a one month break during the protocol should not be enrolled.
  12. Concomitant use other medications known to affect reproductive function or metabolism. These medications include growth hormone, IGF-1, medroxyprogesterone acetate, oral contraceptives, GnRH agonists and antagonists, anti-androgens, gonadotropins, anti-obesity drugs, somatostatin, diazoxide, ACE inhibitors, and calcium channel blockers. The washout period on all these medications will be three months.
  13. Suspected adrenal or ovarian tumor secreting androgens or other ectopic steroid secreting tumor.
  14. Suspected Cushing's syndrome.
  15. Lactose intolerance (the placebo filler is lactose).
  16. Known hypersensitivity to study medication, including ACTH and GnRH, or their excipients.
  17. Any concomitant medical condition that in the opinion of the investigator, may expose a subject to unacceptable level of safety risk, or that affects subject compliance.
  18. Subjects who anticipate having any surgery associated with restricted intake of fluids or radiological studies with contrast dye during the study period.
  19. Any concomitant medical condition that in the opinion of the investigator, may expose a subject to unacceptable level of safety risk, or that affects subject compliance.
  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: NCT01316042

Locations
United States, Indiana
Riley Hospital for Children, Indiana University School of Medicine
Indianapolis, Indiana, United States, 46202
United States, Pennsylvania
Penn State Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
Children's Hospital of Pittsburgh at the University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15224
Sponsors and Collaborators
Milton S. Hershey Medical Center
Investigators
Principal Investigator: Richard S Legro, MD Milton S. Hershey Medical Center
  More Information

Additional Information:
No publications provided

Responsible Party: Richard S. Legro, M.D., Professor, Obstetrics and Gynecology and Public Health Sciences, Milton S. Hershey Medical Center
ClinicalTrials.gov Identifier: NCT01316042     History of Changes
Other Study ID Numbers: 35865
Study First Received: March 15, 2011
Last Updated: June 17, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Milton S. Hershey Medical Center:
Puberty
Hormones

Additional relevant MeSH terms:
Puberty, Precocious
Gonadal Disorders
Endocrine System Diseases
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 31, 2014