Determining the Long-Term Effects of Prenatal Dexamethasone Treatment in Children With 21-Hydroxylase Deficiency and Their Mothers

• ClinicalTrials.gov Identifier: NCT00617292
• Recruitment Status: Unknown
• First Posted: February 18, 2008
• Last Update Posted: December 9, 2008
• Sponsor: Office of Rare Diseases (ORD)
• Information provided by: Office of Rare Diseases (ORD)

Study Description

Brief Summary:

Congenital adrenal hyperplasia (CAH) is a genetic disorder that affects the amount of steroids that the body forms. The most common form of CAH is 21-hydroxylase deficiency (21OHD), which leads to cortisol deficiency and causes the development of mature masculine characteristics in newborn, prepubescent, and grown females, and prepubescent males. Prenatal treatment with dexamethasone, a corticosteroid, has been shown to reduce the masculinization of genitalia. However, the long-term effects of dexamethasone on the children who received it as fetuses and on mothers who were exposed to it while they were pregnant have not been determined. This study will investigate potential long-term adverse side effects of prenatal dexamethasone treatment in children and young adults who received dexamethasone as fetuses and their mothers who were exposed to it during pregnancy.

Condition or disease
Adrenal Hyperplasia, Congenital

Detailed Description:

CAH is a genetic steroidogenesis disorder. The most common form, 21OHD, leads to cortisol deficiency and, in turn, an excess of androgen, a hormone that promotes the development and maintenance of male sex characteristics. As a result of this androgen excess, prepubescent males and newborn, prepubescent, and grown females exhibit mature masculine characteristics. Prenatal treatment with dexamethasone, a corticosteroid that decreases androgen levels, has been shown to prevent the development of abnormal genitalia in female infants. The long-term effects of this treatment, however, have not been evaluated. This study will determine whether prenatal dexamethasone treatment causes any long-term side effects by examining children and young adults who received dexamethasone as fetuses and their mothers, who were exposed to dexamethasone while pregnant.

This study has three parts. In Part 1 of the study, participants will provide written consent for release of their medical records from their physicians. Participants' physicians will then complete a medical form and/or provide copies of selected medical records for each participant. Parts 2 and 3 can be completed in 1 day. In Part 2 of the study, participants will complete questionnaires in their homes. Participants will answer questions about the following experiences: medical procedures, such as hormone treatment and genital surgery; education; work; hobbies; play activities and chores during childhood; identification with the male or female gender; relationships with parents; interest in being a parent; and overall adjustment. Part 3 of the study will consist of neuropsychological testing at the study site. This testing will focus on memory, attention, and overall cognitive abilities.

Study Design

• Study Type: Observational
• Estimated Enrollment: 233 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: Long-Term Outcome in Offspring and Mothers of Dexamethasone-Treated Pregnancies at Risk for Classical Congenital Adrenal Hyperplasia Owing to 21-Hydroxylase Deficiency
• Study Start Date: January 2008
• Estimated Primary Completion Date: July 2009
• Estimated Study Completion Date: July 2009

Groups and Cohorts

Group/Cohort
Category 1, Group 1; Children who have 21OHD and received prenatal dexamethasone treatment
Category 1, Group 2; Children who have 21OHD and did not receive prenatal dexamethasone treatment (control)
Category 2; Mothers of children who received prenatal dexamethasone treatment

Outcome Measures

Primary Outcome Measures :

1. Prevalence of hypertension and obesity [ Time Frame: Throughout the study ]
2. "Normal" masculinization of unaffected females treated prenatally with dexamethasone [ Time Frame: Throughout the study ]
3. Normal masculinization of male fetuses partially treated prenatally with dexamethasone [ Time Frame: Throughout the study ]
4. Memory-related cognitive function [ Time Frame: Throughout the study ]

Eligibility Criteria

• Ages Eligible for Study: 12 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

Participants in this study will include children who received prenatal dexamethasone treatment as fetuses and their mothers.

Criteria

Inclusion Criteria:

For all participants:

• English-speaking
• Has undergone DNA testing for mutations in the CYP21A2 gene

For children who received prenatal dexamethasone treatment:

• Genetic confirmation of 21OHD diagnosis
• Received full or partial prenatal dexamethasone treatment

For children in the control group:

• Did not receive prenatal dexamethasone treatment

For mothers:

• History of at-risk pregnancy for a fetus affected with 21OHD
• Genetic confirmation of child's diagnosis

Exclusion Criteria:

• Any mental disorder that could prevent understanding of study materials
• Current or past steroid use for reasons other than CAH (i.e., asthma, lupus, rheumatoid arthritis)

Contacts and Locations

Contacts

Contact: Claire Gilbert; claire.gilbert@mssm.edu

Locations

United States, New York

Mount Sinai School of Medicine; Recruiting

New York, New York, United States, 10029

Contact: Claire Gilbert, MS 212-241-7099 claire.gilbert@mssm.edu

Principal Investigator: Maria I. New, MD

Sub-Investigator: Madeline Harbison, MD

Sub-Investigator: Karen Lin-Su, MD

Sub-Investigator: Robert Wilson, PhD

Sub-Investigator: Saroj Nimkarn, MD

Sub-Investigator: Susan Baker, PhD

Sub-Investigator: Heino Meyer-Bahlburg, PhD

United States, Texas

University of Texas Southwestern Medical Center; Not yet recruiting

Dallas, Texas, United States, 75390

Contact: Jean Wilson, MD 214-648-3494 jean.wilson@utsouthwestern.edu

Principal Investigator: Jean Wilson, MD

Sub-Investigator: Richard Auchus, MD, PhD

Brazil

University of Sao Paolo; Not yet recruiting

Sao Paolo, SP, Brazil

Contact: Ivo Arnhold, MD 55-11-3069-7512 iarnhold@usp.br

Principal Investigator: Ivo Arnhold, MD

Sub-Investigator: Berenice Mendonca, MD, PhD

France

University of Lyon; Recruiting

Lyon, France

Contact: Pierre Chatelain, MD 04-72-38-58-73 pierre.chatelain@chu-lyon.fr

Principal Investigator: Pierre Chatelain, MD

Sub-Investigator: Maguelone Forest, MD, PhD

Sub-Investigator: Michael David, MD

Sponsors and Collaborators

Office of Rare Diseases (ORD)

Investigators

• Study Chair: Maria I. New, MD; Icahn School of Medicine at Mount Sinai

More Information

• Responsible Party: Maria I. New, MD, Mount Sinai School of Medicine
• ClinicalTrials.gov Identifier: NCT00617292
• Other Study ID Numbers: RDCRN 5610
• First Posted: February 18, 2008
• Last Update Posted: December 9, 2008
• Last Verified: December 2008

Keywords provided by Office of Rare Diseases (ORD):

21-hydroxylase deficiency; 21OHD; CAH

Additional relevant MeSH terms:

Adrenal Hyperplasia, Congenital; Adrenogenital Syndrome; Hyperplasia; Pathologic Processes; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Congenital Abnormalities; Genetic Diseases, Inborn; Steroid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Metabolic Diseases; Adrenal Gland Diseases; Endocrine System Diseases; Gonadal Disorders