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Protocol Details

Androgen Receptor, Implications for Health and Wellbeing: Natural History Study of Individuals with Androgen Insensitivity

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

20-CH-0165

Sponsoring Institute

National Institute of Child Health and Human Development (NICHD)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 1 Years
Max Age: 99 Years

Referral Letter Required

No

Population Exclusion(s)

None

Keywords

Androgen insensitivity syndrome (AIS);
Complete androgen insensitivity (CAIS);
Partial androgen insensitivity (PAIS);
Mild androgen insensitivity syndrome (MAIS);
Natural History

Recruitment Keyword(s)

None

Condition(s)

Androgen insensitivity syndrome;
metabolic parameters in AIS, CAIS, PAIS and MAIS;
Tumor Formation in AIS, CAIS, PAIS and MAIS;
Sexual Function AIS, CAIS, PAIS and MAIS

Investigational Drug(s)

None

Investigational Device(s)

None

Intervention(s)

None

Supporting Site

National Institute of Child Health and Human Development

Background:

Androgen effects in humans are usually (but not always) mediated by the androgen receptor which is coded for by the androgen receptor gene (AR gene). Androgen Insensitivity Syndrome (AIS) is a rare condition in which the body cannot sense the male hormones in the blood or tissue. Both women and men can be affected by AIS. Researchers want to learn more about the health of people with AIS over time.

With a natural history study in individuals with AIS, data and tests may provide information regarding health risks (including the risks and benefits of gonadectomy and best ways to monitor for tumor) and optimal management of individuals with AIS as well as elucidate the role of the androgen receptor in human health. This study does not involve any interventions and we can provide clinical care while collecting data.

Objective:

The objective of this natural history study is to describe and define a comprehensive phenotype (characteristic) of patients with AIS based on confirmed androgen receptor (AR) gene difference. We will evaluate hormones, bone density and markers, cardiovascular and metabolic parameters, as well as quality of life and tumor formation risk and evaluation. The purpose is to obtain a better understanding of the overall health issues that people with AIS may have through the study procedures listed.

Eligibility:

People ages 0-99 with AIS and their adult relatives

Design:

Participants will go through a series of study procedures for data and specimen collection. This will be done to understand how AIS affects individuals since the androgen receptor is found in many tissues in the body including skin, bone, muscle, and the neurologic, immune and metabolic systems. All tests will be performed by skilled and trained study professionals.

Participants will be screened with:

Medical history

Physical exam

Medical record review

Lab tests.

Participants will have physical exams. Their body measurements will be taken. They will have blood and urine tests. They will have electrocardiograms to check heart health. They may complete questionnaires. They may have an Oral Glucose Tolerance Test.

Participants may have x-rays taken of the hand, wrist, and other bones.

Participants will have body scans to measure bone thickness.

Participants will have magnetic resonance imaging (MRI) or sonogram of the pelvis. For MRI, they may get a contrast agent via intravenous (IV) catheter.

Adult participants may have the following:

MR elastography. It uses MRI and low-frequency vibrations to map stiffness of body tissues.

MR spectroscopy. It uses MRI to take pictures of chemicals in the liver and body fat.

Cardiac computed tomography scan. It uses x-rays to make pictures of the heart. Participants may get a contrast agent via IV.

Optional genital exam.

Participants will have visits every 1-2 years. Participation lasts indefinitely.

Adult relatives will also be invited to participate but will have only 1 visit. It will include some of the above tests.

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Eligibility

INCLUSION CRITERIA:

Inclusion Criteria for AIS subjects

In order to be eligible to participate in this study, an individual must meet all the following criteria:

1) Individuals ages 0-99 years old with known androgen insensitivity based on pathologic androgen receptor gene mutation or based on clinical diagnosis of complete androgen insensitivity (CAIS) based on 46 XY karyotype, presence of testis, absence of uterus, high testosterone without signs of virilization at birth or during puberty and/or multiple members in the family also presenting with clinical CAIS.

2) Identify as male or female

3) Patients with both complete, partial and mild androgen insensitivity are eligible

4) Stated willingness to comply with all study procedures and availability for the duration of the study

5) Ability of subject or guardian to understand and the willingness to sign and date a written informed consent document.

Inclusion Criteria for Relative of AIS subjects

1) Adult Relatives of patients with AIS

EXCLUSION CRITERIA:

Exclusion Criteria for AIS subjects

1) An individual who meets any of the following criteria will be excluded from participation in this study: Patients with other diagnosis such as partial or complete gonadal dysgenesis, 5-alpha reductase deficiency, and 46 XY. If, following a diagnostic work-up, a patient is determined to have causes for 46 XY DSD other than androgen insensitivity; they will no longer be followed on this protocol. They will have the opportunity to continue care with the team under the Data Collection Protocol or may be referred to an expert or multidisciplinary DSD team in the community.

2) Patients with significant non-endocrine medical conditions.

Exclusion Criteria for Relative of AIS subjects

1) Patients with significant non-endocrine medical conditions.


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Citations:

Deans R, Creighton SM, Liao LM, Conway GS. Timing of gonadectomy in adult women with complete androgen insensitivity syndrome (CAIS): patient preferences and clinical evidence. Clin Endocrinol (Oxf). 2012 Jun;76(6):894-8. doi: 10.1111/j.1365-2265.2012.04330.x. PMID: 22211628.

Ahmed SF, Cheng A, Dovey L, Hawkins JR, Martin H, Rowland J, Shimura N, Tait AD, Hughes IA. Phenotypic features, androgen receptor binding, and mutational analysis in 278 clinical cases reported as androgen insensitivity syndrome. J Clin Endocrinol Metab. 2000 Feb;85(2):658-65. doi: 10.1210/jcem.85.2.6337. PMID: 10690872.

Bertelloni S, Meriggiola MC, Dati E, Balsamo A, Baroncelli GI. Bone Mineral Density in Women Living with Complete Androgen Insensitivity Syndrome and Intact Testes or Removed Gonads. Sex Dev. 2017;11(4):182-189. doi: 10.1159/000477599. Epub 2017 Jul 18. PMID: 28715798.

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Contacts:

Principal Investigator

Referral Contact

For more information:

Veronica Gomez-Lobo, M.D.
National Institute of Child Health and Human Development (NICHD)
NIHBC 10 - CLINICAL CENTER BG RM 8N248B
10 CENTER DR
BETHESDA MD 20892
(301) 435-7567
veronica.gomez-lobo@nih.gov

Veronica Gomez-Lobo, M.D.
National Institute of Child Health and Human Development (NICHD)
NIHBC 10 - CLINICAL CENTER BG RM 8N248B
10 CENTER DR
BETHESDA MD 20892
(301) 435-7567
veronica.gomez-lobo@nih.gov

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: TTY Users Dial 7-1-1
ccopr@nih.gov

Clinical Trials Number:

NCT04708431

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