Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
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.
Androgen Insensitivity Syndrome
Metabolic parameters in ais, pier, parents and more
Tumor formation in ais, pier, parents and more
Sexual function ais, pier, parents and more
Study Description: This is a natural history study of individuals with androgen receptor gene abnormalities. Objectives: 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 AIS, as well as quality life and tumor formation risk and evaluation. Secondary Objectives: 1. Bone Health: - Follow a large population of patients with androgen receptor abnormalities for: * Longitudinal assessment of bone mineral density (BMD) before and after gonadectomy * Development of normative values for dual-energy X-ray absorptiometry (DEXA) scans in individual with complete androgen insensitivity syndrome (CAIS) * Studies to determine bone geometry, strength and shape, * Studies to determine muscle-skeletal unit inferences * Studies to evaluate skin tone * Evaluation of bone accrual from infancy to adolescence 2. Metabolic and Immune Abnormalities: - Follow a large population of patients with androgen receptor abnormalities for studies of metabolic abnormalities and auto-immune disease screening * Metabolic syndrome, * Insulin resistance * Cardiovascular markers * Endometabolic imaging * Autoimmune screening tests 3. Testicular Tumor Risk and Monitoring: - Follow a large population of patients with androgen receptor abnormalities in order to: -- Describe the typical and atypical appearance of testes on ultrasound and magnetic resonance imaging (MRI) in young individual with CAIS. * Evaluate gonadal tumor markers as a tool to assess for gonadal tumor. - When individuals with androgen receptor abnormalities decide to undergo gonadectomy, perform tissue evaluation in order to: * Investigate the pathophysiology of gonadal tumor formation * Assess fertility potential in testis of individual with androgen receptor abnormalities 4. Quality of Life: * Follow a large population of patients with androgen receptor abnormalities to characterize quality of life measures throughout the lifespan * Evaluate the effects of androgen receptor abnormalities on individual s sexual function. Compare sexual function in adult individuals with androgen receptor abnormalities to individual with classic congenital adrenal hyperplasia (CAH) and unaffected individual of similar ages. 5. Hormone Replacement: - Evaluate different types and delivery of hormone replacement therapy on quality of life, sexual function, bone health and metabolic parameters in individual who have undergone gonadectomy 6. Follow a sample population of relatives of individuals with androgen insensitivity syndrome (AIS) in order to assess the effects of AR gene difference carrier status phenotype including hormonal, metabolic, immunologic, quality of life, and tumor formation. Family members without AR gene abnormalities will serve as controls. Follow a large population of patients with AIS for referral to future treatment studies. Endpoints: Primary Endpoint: Longitudinal evaluation of 500 individuals with AIS. Secondary: * DEXA scans and bone metabolism markers will be evaluated longitudinally in all individuals with AIS. Additionally, these will be correlated with muscle grip and skin tone studies. * Compare metabolic parameters in all individuals with AIS. * Compare gonadal tissue with MRI or ultrasound in all individuals with AIS. * Evaluate Quality of life with Quality of life (QoL) questionnaire.
| Study Type : | OBSERVATIONAL |
| Estimated Enrollment : | 650 participants |
| Official Title : | Androgen Receptor, Implications for Health and Wellbeing: Natural History Study of Individuals With Androgen Insensitivity |
| Actual Study Start Date : | 2021-04-29 |
| Estimated Primary Completion Date : | 2040-02-01 |
| Estimated Study Completion Date : | 2040-02-01 |
Information not available for Arms and Intervention/treatment
| Ages Eligible for Study: | 1 Year to 99 Years |
| Sexes Eligible for Study: | ALL |
| Accepts Healthy Volunteers: | 1 |
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RECRUITING
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892