Androgen Receptor, Implications for Health and Wellbeing: Natural History Study of Individuals With Androgen Insensitivity
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Enrollment
- 650
- Locations
- 1
- Primary Endpoint
- To define and describe a comprehensive phenotype in 500 patients with androgen insensitivity
Study Overview
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.
Detailed Description
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.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 8 Years to 99 Years (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •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:
- •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.
- •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.
- •Inclusion Criteria for Relative of AIS Subjects
- •1) Adult Relatives of patients with AIS
Exclusion Criteria
- •Exclusion Criteria for AIS Subjects
- •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.
- •Patients with significant non-endocrine medical conditions.
- •Exclusion Criteria for Relative of AIS Subjects
- •1) Patients with significant non-endocrine medical conditions.
Arms & Interventions
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.
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
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
Outcomes
Primary Outcomes
To define and describe a comprehensive phenotype in 500 patients with androgen insensitivity
Time Frame: End of study
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
Secondary Outcomes
- Evaluate Bone Health in individuals with Androgen Insensitivity(End of study)
- Metabolic assessment in individuals with Androgen Insensitivity(End of study)
- Gonadal Tumor evaluation in individuals with Androgen Insensitivity(End of study)
- Quality of life measures (QoL) in individuals with Androgen Insensitivity(End of study)
- Effects of hormone therapy in individuals with Androgen Insensitivity(End of study)
- Effects of hormone therapy in individuals with Androgen Insensitivity(End of study)
- Gonadal Tumor evaluation in individuals with Androgen Insensitivity(End of study)
- Quality of life measures (QoL) in individuals with Androgen Insensitivity(End of study)
- Evaluate Bone Health in individuals with Androgen Insensitivity(End of study)
- Metabolic assessment in individuals with Androgen Insensitivity(End of study)