Initiating Transdermal Estradiol Therapy in Turner's Syndrome

NCT00870220 | Terminated Phase 1 DMC

• 1 other identifier: 15327B
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 3

Brief Summary

This is a multicenter, randomized, controlled, semi-blinded study to compare two low doses of estradiol administered by recently available transdermal patches for the initiation of puberty in Turner syndrome girls 11.5-13.0 years old in conjunction with growth hormone (GH) therapy. The specific hypotheses to be tested are: when combined with growth hormone (GH) treatment, low dose transdermal estradiol (LTE2) replacement will be more effective in stimulating feminization, height velocity, and bone mineral density without compromising growth potential than very low dose transdermal estradiol (VLTE2), which will in turn be superior to GH alone in effects on feminization, height velocity, and bone mineral density.

Conditions

Turner's Syndrome

Keywords

Turner's Syndrome

Outcome Measures

Primary Outcomes (1)

• The net change of height velocity between Group 2 and Group 3 and the net change in predicted height between Group 2 and Group 3.

  12 months

Secondary Outcomes (1)

• Plasma E2 level to document the dose-response effect of the applied prescription and uterine dimensions to quantitate the estrogenic effect on growth and development of the uterus.

  12 months

Study Arms (1)

GH alone, Low dose E2 patch, Very Low-dose E2 patch

EXPERIMENTAL

Group 1: Growth hormone alone, no E2. Group 2: Growth Hormone plus Estradiol patch dose A(14 mcg/d x 10 d) x 6 months then Estradiol patch dose B(25 mcg/d x 10 d) x 6 months. Group 3: Growth Hormone plus Estradiol patch dose B(25 mcg/d x 10 d) x 6 months then Estradiol patch dose C(25 mcg/d x 3 w) x 6 months.

Drug: Norditropin, Menostar 14mcg patch, Vivelle dot 25mcg patch

Interventions

Norditropin, Menostar 14mcg patch, Vivelle dot 25mcg patch DRUG

GH will be maintained at 0.05mg/kg/d, adjusted every 3 months. Estradiol 14mcg patch will be applied for 10 days/month for the first 6 months in Group 2. Estradiol 25mcg patch will be applied for 10 days/month for the second 6 months in Group 2, and for the first 6 months in Group 3. Estradiol 25mcg patch will be applied for 3 weeks per month for the second 6 months in Group 3.

Also known as: Norditropin, Menostar patch, Vivelle dot patch

GH alone, Low dose E2 patch, Very Low-dose E2 patch

Eligibility Criteria

• Age: 138 Months - 13 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• subjects will be recruited from participating Pediatric Endocrinology Clinics in the United States.
• Subjects will be 11.5-13.0 years of age and must have completed at least 6 months of GH therapy prior to the study.
• Subjects may not have had any estrogen prior to the study. All subjects must be breast stage 1 and euthyroid prior to the study
• Those on thyroid medication will continue the appropriate thyroid replacement therapy during the study.

You may not qualify if:

• On estrogen therapy, breast stage 2 or greater, not on GH for at least 6 months.

Sponsors & Collaborators

• University of Chicago: lead
• Novo Nordisk A/S: collaborator
• University of Michigan: collaborator
• Johns Hopkins University: collaborator
• Massachusetts General Hospital: collaborator
• University of Oklahoma: collaborator
• University of South Florida: collaborator
• Thomas Jefferson University: collaborator

Study Sites (3)

University of Chicago

Chicago, Illinois, 60637, United States

Location

John Hopkins University

Baltimore, Maryland, 21287, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Conditions

Turner Syndrome

Interventions

Human Growth Hormone; Estradiol; Transdermal Patch

Condition Hierarchy (Ancestors)

Gonadal Dysgenesis; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Sex Chromosome Disorders of Sex Development; Male Urogenital Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Sex Chromosome Disorders; Chromosome Disorders; Genetic Diseases, Inborn; Gonadal Disorders; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Growth Hormone; Pituitary Hormones, Anterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Equipment and Supplies

Study Officials

• Robert L. Rosenfield, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2009
• First Posted: March 27, 2009
• Study Start: April 1, 2009
• Primary Completion: March 1, 2011
• Study Completion: March 1, 2011
• Last Updated: March 11, 2014

Record last verified: 2014-03

Locations

US (3)