Recruiting

Androgen Insensitivity Syndrome

Sponsor:

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Code:

NCT04708431

Conditions

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

Eligibility Criteria

Sex: All

Age: 8 - 70+

Healthy Volunteers: Accepted

Study Details

Brief summary:

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 8-99 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 and HRpQCT scans 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.

Optional one-time vaginal swab.

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.

Conditions

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

Study ID

NCT04708431

Start date

Apr 29, 2021

Status verified date

Aug 11, 2026

Completion date

Feb 1, 2040

Anticipated

Primary completion date

Feb 1, 2040

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 8 - 70+

Healthy Volunteers: Accepted

  • 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 8-99 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 diagnoses 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.

Study Design

Enrollment

650 participants

Anticipated

Interventions and Outcome Measures

Arms

Female subjects relatives who are carriers of the AR gene difference

We will enroll 50 female subjects relatives AIS subjects who are carriers of the AR gene difference

Female subjects relatives who are not carriers of the AR gene

We will enroll 50 female subjects relatives of AIS subjects who are not carriers of the AR gene.

Healthy male subjects relatives

We will enroll 50 healthy male subjects of AIS relative subjects

Subjects with androgen receptor mutations

500 Subjects with confirmed androgen receptor mutations

Primary outcome measure

  • To define and describe a comprehensive phenotype in 500 patients with androgen insensitivity [ Time Frame: End of study ]

Central Contacts and Locations

Central contacts

Veronica Gomez-Lobo, M.D.

(301) 435-7567veronica.gomez-lobo@nih.gov

Locations

National Institutes of Health Clinical Center

Recruiting

Bethesda, Maryland, United States, 20892

Contacts

For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

800-411-1222prpl@cc.nih.gov

More Information

Sponsor

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Last update posted

Aug 13, 2026

Last verified

Aug 11, 2026

Keywords

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) on 2026-08-13.