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

NCT04708431 | Recruiting

• 2 other identifiers: 20016520-CH-0165
• Study Type: observational
• Target: 650
• Locations: 1 country
• Sites: 1

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 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 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. 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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• To define and describe a comprehensive phenotype in 500 patients with androgen insensitivity

  Primary Objectives: To define and describe a comprehensive phenotype of patients with androgen insensitivity (based on confirmed androgen receptor (AR) gene difference), including hormonal, metabolic, immunologic, and cardiovascular aspects of the disease, as well as quality life and tumor formation risk and evaluation

  End of study

Secondary Outcomes (5)

• Effects of hormone therapy in individuals with Androgen Insensitivity

  End of study

• Quality of life measures (QoL) in individuals with Androgen Insensitivity

  End of study

• Gonadal Tumor evaluation in individuals with Androgen Insensitivity

  End of study

• Metabolic assessment in individuals with Androgen Insensitivity

  End of study

• Evaluate Bone Health in individuals with Androgen Insensitivity

  End of study

Study Arms (4)

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

Eligibility Criteria

• Age: 1 Year - 99 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

We will enroll and evaluate 500 patients with confirmed androgen receptor mutations. We will enroll 50 female relatives who are carriers of the AR gene difference and 50 female relatives who are not carriers of the AR gene and 50 healthy male relatives.

You may qualify if:

• In order to be eligible to participate in this study, an individual must meet all the following criteria:
• 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.
• Identify as male or female
• Patients with both complete, partial and mild androgen insensitivity are eligible
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Ability of subject or guardian to understand and the willingness to sign and date a written informed consent document.
• \) Adult Relatives of patients with AIS

You may not qualify if:

• 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.
• Patients with significant non-endocrine medical conditions.
• \) Patients with significant non-endocrine medical conditions.

Sponsors & Collaborators

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

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (3)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Androgen-Insensitivity Syndrome; Bulbo-Spinal Atrophy, X-Linked

Condition Hierarchy (Ancestors)

Disorder of Sex Development, 46,XY; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Gonadal Disorders; Endocrine System Diseases; Muscular Atrophy, Spinal; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Motor Neuron Disease; Neuromuscular Diseases

Study Officials

• Veronica Gomez-Lobo, M.D.

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Veronica Gomez-Lobo, M.D.

CONTACT

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

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2021
• First Posted: January 14, 2021
• Study Start: April 29, 2021
• Primary Completion (Estimated): February 1, 2040
• Study Completion (Estimated): February 1, 2040
• Last Updated: March 13, 2026

Record last verified: 2026-03-11

Locations

US (1)