Metformin for the Treatment of Premature Pubarche in Girls

NCT ID: NCT01316042

Last Updated: 2016-05-12

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-05-31
• Study Completion Date: 2014-04-30

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.

Conditions

Premature Pubarche

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

sugar pill

2 pills per day for 12 months

Group Type: PLACEBO_COMPARATOR

sugar pill

Intervention Type: DRUG

2 pills per day for 12 months

Metformin

2 212.5mg pill/day for 12 months

Group Type: ACTIVE_COMPARATOR

Metformin, glucophage

Intervention Type: DRUG

2 212.5mg pills/day for 12 months

Interventions

sugar pill

2 pills per day for 12 months

Intervention Type: DRUG

Metformin, glucophage

2 212.5mg pills/day for 12 months

Intervention Type: DRUG

Other Intervention Names

metformin

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.

• Minimum Eligible Age: 4 Years
• Maximum Eligible Age: 10 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Milton S. Hershey Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Richard S. Legro, M.D.

Professor, Obstetrics and Gynecology and Public Health Sciences

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Richard S Legro, MD

Role: PRINCIPAL_INVESTIGATOR

Milton S. Hershey Medical Center

Locations

Riley Hospital for Children, Indiana University School of Medicine

Indianapolis, Indiana, United States

Penn State Hershey Medical Center

Hershey, Pennsylvania, United States

Children's Hospital of Pittsburgh at the University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Countries

United States

Other Identifiers

35865

Identifier Type: -

Identifier Source: org_study_id