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

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

Sponsoren

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

Quelle National Institutes of Health Clinical Center (CC)
Kurze Zusammenfassung

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). Individuals with abnormalities of this receptor gene can present with androgen insensitivity syndrome (AIS). There are a variety of phenotypes including complete female phenotype (complete androgen insensitivity or CAIS), ambiguous genitalia in cases of partial androgen insensitivity (PAIS) and male phenotype associated with infertility of hypospadias in mild cases of AIS. Complete androgen insensitivity is a rare condition with an estimated incidence of 1:20,000-64,000, while PAIS is rarer still and mild AIS has likely not been studied enough to ascertain it s prevalence. Individuals with complete and partial AIS present some management conundrums as traditionally they have undergone gonadectomy in order to avoid gonadal tumors as well as pubertal virilization in girls with PAIS. Because this is a rare condition, little is known regarding the risks and benefits of gonadectomy, optimal hormone replacement after gonadectomy as well as general health in individuals with these conditions. Furthermore, the androgen receptor is found in many tissues in the body including skin, bone, muscle, and the neurologic, immune and metabolic systems. Finally, some testosterone effects may be through mechanisms other than AR receptor and these are not well understood. A natural history study in individuals with AIS may provide information regarding health risks and optimal management of individuals with AIS as well as elucidate the role of the androgen receptor in human health.

detaillierte Beschreibung

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). Individuals with abnormalities of this receptor gene can present with androgen insensitivity syndrome (AIS). There are a variety of phenotypes including complete female phenotype (complete androgen insensitivity or CAIS), ambiguous genitalia in cases of partial androgen insensitivity (PAIS) and male phenotype associated with infertility of hypospadias in mild cases of AIS. Complete androgen insensitivity is a rare condition with an estimated incidence of 1:20,000-64,000, while PAIS is rarer still and mild AIS has likely not been studied enough to ascertain it s prevalence. Individuals with complete and partial AIS present some management conundrums as traditionally they have undergone gonadectomy in order to avoid gonadal tumors as well as pubertal virilization in girls with PAIS. Because this is a rare condition, little is known regarding the risks and benefits of gonadectomy, optimal hormone replacement after gonadectomy as well as general health in individuals with these conditions. Furthermore, the androgen receptor is found in many tissues in the body including skin, bone, muscle, and the neurologic, immune and metabolic systems. Finally, some testosterone effects may be through mechanisms other than AR receptor and these are not well understood. A natural history study in individuals with AIS may provide information regarding health risks and optimal management of individuals with AIS as well as elucidate the role of the androgen receptor in human health.

Gesamtstatus Not yet recruiting
Anfangsdatum January 20, 2021
Fertigstellungstermin February 1, 2040
Primäres Abschlussdatum February 1, 2040
Studientyp Observational
Primärer Ausgang
Messen Zeitfenster
To define and describe a comprehensive phenotype in 500 patients with androgen insensitivity End of study
Sekundäres Ergebnis
Messen Zeitfenster
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
Einschreibung 650
Bedingung
Teilnahmeberechtigung

Probenahmeverfahren: Non-Probability Sample

Kriterien:

- 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 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. INCLUSION OF VULNERABLE PARTICIPANTS Participation of Children Children will be included in this protocol as AIS is often diagnosed early in life and has effects on puberty and development. Every effort will be made to protect children s rights and safety. Participation of Employees NIH employees may be enrolled in this study as this population meets the study entry criteria. Neither participation nor refusal to participate as a subject in the research will have an effect, either beneficial or adverse, on the participant s employment or position at NIH.

Geschlecht: All

Mindestalter: N/A

Maximales Alter: 99 Years

Gesunde Freiwillige: Accepts Healthy Volunteers

Insgesamt offiziell
Nachname Rolle Zugehörigkeit
Veronica Gomez-Lobo, M.D. Principal Investigator Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Gesamtkontakt

Nachname: Veronica Gomez-Lobo, M.D.

Telefon: (301) 435-7567

Email: [email protected]

Ort
Einrichtung: Kontakt: National Institutes of Health Clinical Center For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 TTY8664111010 [email protected]
Standort Länder

United States

Überprüfungsdatum

January 12, 2021

Verantwortliche Partei

Art: Sponsor

Schlüsselwörter
Hat den Zugriff erweitert No
Bedingung Durchsuchen
Armgruppe

Etikette: Female subjects relatives who are carriers of the AR gene diff

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

Etikette: Female subjects relatives who are not carriers of the AR gene

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

Etikette: Healthy male subjects relatives

Beschreibung: We will enroll 50 healthy male subjects of AIS relative subjects

Etikette: Subjects with androgen receptor mutations

Beschreibung: 500 Subjects with confirmed androgen receptor mutations

Studiendesign Info

Beobachtungsmodell: Cohort

Zeitperspektive: Prospective

Quelle: ClinicalTrials.gov