Clinical trial NCT01316042: Metformin for the Treatment of Premature Pubarche in Girls
Official title: A Double Blind Randomized Controlled 12 Month Trial of Metformin for the Treatment of Premature Pubarche in Girls
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Premature Pubarche
Keywords: Puberty
Hormones
Lead sponsor: Milton S. Hershey Medical Center
Sponsor class: OTHER
First posted: 2011-03-16
Enrollment: 4
Sex: FEMALE
Minimum age (years): 4
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: Change in Serum DHEAS Levels
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Riley Hospital for Children, Indiana University School of Medicine
state: Indiana
city: Hershey
country: United States
facility: Penn State Hershey Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh at the University of Pittsburgh Medical Center
state: Pennsylvania
Study officials:
affiliation: Milton S. Hershey Medical Center
name: Richard S Legro, MD
role: PRINCIPAL_INVESTIGATOR
References: