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Examining Genetic Differences Among People With 21-Hydroxylase Deficiency

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ClinicalTrials.gov Identifier: NCT00542841
Recruitment Status : Completed
First Posted : October 12, 2007
Last Update Posted : December 14, 2015
Sponsor:
Collaborators:
Office of Rare Diseases (ORD)
National Center for Research Resources (NCRR)
Information provided by (Responsible Party):
Maria I. New, Icahn School of Medicine at Mount Sinai

Study Description
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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. This, in turn, causes the development of mature masculine characteristics in newborn, prepubescent, and grown females and in prepubescent males. 21OHD is known to be caused by the mutation of a specific gene. However, symptom severity among people with 21OHD varies, and adults seem to be less affected than children. This study will examine participants' DNA to determine what other genes may affect the severity of 21OHD and may make the disease milder in adults than in children.

Condition or disease Intervention/treatment Phase
21-hydroxylase Deficiency Procedure: Hydrocortisone withdrawal Not Applicable

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. The symptoms and severity of 21OHD vary among individuals with the disease and in adults versus children. The reasons for these differences are not yet known. Current therapy for 21OHD consists of administration of glucocorticoids to replace cortisol and suppress excessive pituitary function. With more information about what genes or factors contribute to the severity of 21OHD, researchers may be able to better treat children and adults with the disease. This study will examine participants' DNA to determine what other genes may affect the severity of 21OHD and may make the disease milder in adults than in children.

People interested in participating in this 3-day inpatient study will first undergo a physical exam and provide a blood sample to determine eligibility. Eligible participants will be admitted to the study site in the morning on the first study day. A blood sample will be taken and participants will receive one 10-mg pill of hydrocortisone. Heart rates and blood pressures will be taken every 4 hours throughout the day. In the morning of Day 2, a blood sample will be taken and participants will be asked to urinate in the toilet. After this point and until the end of the study, participants will collect all urine in a jug. On the morning of Day 3, participants will complete urine collection and a blood sample will be taken. Participants will then receive intravenously a medicine called cosyntropin, a synthetic form of a hormone that the body makes. About 1 hour after this, participants will provide a final blood sample. Participants will receive one last pill of hydrocortisone prior to the end of the study.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 99 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Modifier Genes in 21-Hydroxylase Deficiency
Study Start Date : August 2007
Actual Primary Completion Date : March 2009
Actual Study Completion Date : March 2009

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: 1 Procedure: Hydrocortisone withdrawal
This is considered a non-standard treatment. On Day 1, participants will receive one 10-mg pill of hydrocortisone. On Day 3, participants will receive intravenously a medicine called cosyntropin, a synthetic form of a hormone that the body makes. Participants will receive one last pill of hydrocortisone prior to the end of the study.


Outcome Measures
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Primary Outcome Measures :
  1. Serum 17-hydroxyprogesterone/cortisol ratio [ Time Frame: After cosyntropin administration ]

Secondary Outcome Measures :
  1. Many other serum and urine steroids, metabolites, and precursors [ Time Frame: Before and after cosyntropin administration ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of 21OHD with two "severe" alleles, excluding the A/C656G mutation OR participant consents to genetic testing and a CYP21A2 mutation is identified
  • Currently a patient at one of the participating centers
  • Currently taking less than 15mg/m² hydrocortisone per day and has been for at least the past 3 months

Exclusion Criteria:

  • History of adrenal crisis within 1 year prior to study entry
  • Any coexisting condition requiring corticosteroid therapy (e.g., asthma, psoriasis)
  • History of removal of both adrenal glands
  • History of deficient pituitary gland function
  • Current or past use of growth hormone therapy within 3 months prior to study entry
  • Serum creatinine level greater than 2 mg/dL
  • Systolic blood pressure less than 90 mm Hg
  • History of critical illness or surgery that required general anesthesia within 1 month prior to study entry
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00542841


Locations
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United States, New York
Mount Sinai School of Medicine
New York, New York, United States, 10029
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
Brazil
University of Sao Paolo
Sao Paolo, SP, Brazil, 06403-900
Sponsors and Collaborators
Maria I. New
Office of Rare Diseases (ORD)
National Center for Research Resources (NCRR)
Investigators
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Principal Investigator: Richard J. Auchus, MD, PhD University of Texas Southwestern Medical Center
More Information
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Responsible Party: Maria I. New, Professor, Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov Identifier: NCT00542841    
Other Study ID Numbers: RDCRN 5607
U54RR019484 ( U.S. NIH Grant/Contract )
RR019484
First Posted: October 12, 2007    Key Record Dates
Last Update Posted: December 14, 2015
Last Verified: December 2015
Keywords provided by Maria I. New, Icahn School of Medicine at Mount Sinai:
Adrenal Hyperplasia, Congenital
Steroid Biosynthesis Disorders
Additional relevant MeSH terms:
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Adrenal Hyperplasia, Congenital
Adrenogenital Syndrome
Disorders of Sex Development
Urogenital Abnormalities
Congenital Abnormalities
Genetic Diseases, Inborn
Steroid Metabolism, Inborn Errors
 Metabolism, Inborn Errors
Metabolic Diseases
Adrenal Gland Diseases
Endocrine System Diseases
Gonadal Disorders
Hydrocortisone
Anti-Inflammatory Agents