INSL3 as a Biomarker of Pubertal Activation: Role in Evaluating Precocious and Delayed Puberty (INSL3GNRH)
INSL3 as an Early Marker of Pubertal Activation: Evaluation of Its Potential Role as a New Biomarker in the Diagnosis of Central Precocious Puberty and Delayed Puberty.
This is an observational study in children up to 16 years old who are suspected of having central precocious puberty or delayed puberty. The main questions it aims to answer are:
- Can the level of insulin-like peptide 3 (INSL3) predict if a child's puberty has truly started?
- Can this marker help reduce the need for more complex and invasive tests?
Participants will:
- Give one extra blood sample just before starting the standard gonadotropin-releasing hormone (GnRH) stimulation test (during the baseline blood draw).
- Have this extra sample used to measure the INSL3 hormone.
- Complete the rest of the GnRH test as prescribed by their doctor.
Researchers will compare the INSL3 hormone levels in children who have a positive GnRH test to those who have a negative test. This will help researchers learn if INSL3 can be used as a new, simple tool to diagnose early or delayed puberty.
Visão geral do estudo
Status
Condições
Descrição detalhada
Diagnosing the exact onset of puberty, especially in its early stages, is a clinical challenge. Currently, the gonadotropin-releasing hormone (GnRH) stimulation test is the gold standard for evaluating hypothalamic-pituitary-gonadal (HPG) axis activation. However, this test is invasive, time-consuming, expensive, and may have limited sensitivity during the very early phases of Central Precocious Puberty (CPP) or Delayed Puberty (DP).
INSL3 is produced constitutively by Leydig cells in males and theca cells of growing antral follicles in females. Unlike other hormones which are secreted with acute and pulsatile patterns, INSL3 exhibits minimal circadian variation and reflects the continuous maturation of gonadal tissues.
The purpose of this study is to evaluate INSL3 as an early marker of pubertal activation. By correlating basal INSL3 levels, measured via ELISA, with the outcomes of standard GnRH tests and other clinical parameters, the investigators hope to determine if INSL3 can accurately predict HPG axis activation. Ultimately, validating this biomarker could lead to a simpler, single-sample diagnostic approach, reducing the burden of dynamic stimulation testing in pediatric practice.
Tipo de estudo
Inscrição (Estimado)
Contactos e Locais
Contato de estudo
- Nome: Federico Baronio, MD, PhD
- Número de telefone: 00390512144816
- E-mail: federico.baronio@aosp.bo.it
Locais de estudo
-
-
-
Bologna, Itália, 40138
- Recrutamento
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Bologna 40138
-
Contato:
- Federico Baronio, MD, PhD
- Número de telefone: 00390512144816
- E-mail: federico.baronio@aosp.bo.it
-
-
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Método de amostragem
População do estudo
Pediatric patients of both sexes, aged 0 to 16 years, who are followed for suspected Central Precocious Puberty (CPP) or suspected Delayed Puberty (DP) at the Pediatric Endocrinology Unit of the IRCCS Azienda Ospedaliero-Universitaria of Bologna. These patients must have a clinical indication to undergo a standard GnRH stimulation test as part of their routine diagnostic workup for pubertal evaluation.
Descrição
Inclusion Criteria:
- Age between 0 and 16 years at the time of enrollment.
- Males with suspected Central Precocious Puberty (CPP), defined by a testicular volume ≥4 mL before 9 years of age.
- Females with suspected CPP, defined by the onset of thelarche before 8 years of age.
- Males with suspected Delayed Puberty (DP), defined by testicular volume <4 mL by 14 years of age.
- Females with suspected DP, defined by the absence of thelarche by 13 years of age.
- Written informed consent for study participation and personal data processing provided by the parents/legal guardians, with the assent of the participating minor.
Exclusion Criteria:
- Presence of congenital or acquired conditions known to primarily alter pubertal development or gonadal function, regardless of HPG axis physiology (e.g., disorders of sex development, anorchia, previous ovariectomy, uncorrected bilateral cryptorchidism, previous iatrogenic gonadotoxicity).
- Primary endocrine diseases interfering with hypothalamic-pituitary-gonadal axis regulation (e.g., congenital hypogonadotropic hypogonadism, panhypopituitarism).
- Use of hormonal therapies or drugs capable of modifying gonadal function or the response to the GnRH test (e.g., exogenous sex steroids, androgens/anabolic steroids).
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Modelos de observação: COHORT
- Perspectivas de Tempo: PROSPECTIVE
Coortes e Intervenções
Grupo / Coorte |
|---|
|
Suspected Central Precocious Puberty (CPP)
Pediatric patients (males under 9 years, females under 8 years) with clinical signs of early pubertal onset, undergoing a standard GnRH stimulation test. |
|
Suspected Delayed Puberty (DP)
Pediatric patients (males 14 years and older, females 13 years and older) with absent signs of puberty, undergoing a standard GnRH stimulation test. |
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Baseline INSL3 Concentration as a Predictor of GnRH Test Outcome
Prazo: Baseline (prior to GnRH test administration)
|
Assessment of baseline Insulin-like peptide 3 (INSL3) levels (measured in pg/ml) and their association with the gonadotropin response to the standard GnRH stimulation test (evaluated by peak LH, peak FSH in mU/ml, and LH/FSH ratio) to determine Hypothalamic-Pituitary-Gonadal (HPG) axis activation in patients with suspected precocious or delayed puberty. |
Baseline (prior to GnRH test administration)
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Diagnostic Accuracy of Combined INSL3 and Clinical Parameters
Prazo: Baseline
|
Evaluation of whether integrating baseline INSL3 (pg/ml) with other clinical and laboratory parameters (bone age in years, uterine longitudinal diameter in cm and volume in ml, basal LH/FSH in mU/ml, estradiol in pg/ml, and testosterone in ng/ml) improves the ability to distinguish patients with a positive GnRH test from those with a negative test. |
Baseline
|
|
Correlation Between INSL3 and Pubertal Development Parameters
Prazo: Baseline
|
Assessment of the correlation between baseline INSL3 levels (pg/ml) and key physiological parameters of pubertal development, including bone age, baseline gonadotropins, sex steroids, and, in females, uterine dimensions. |
Baseline
|
Colaboradores e Investigadores
Patrocinador
Publicações e links úteis
Publicações Gerais
- Anand-Ivell R, Tremellen K, Dai Y, Heng K, Yoshida M, Knight PG, Hale GE, Ivell R. Circulating insulin-like factor 3 (INSL3) in healthy and infertile women. Hum Reprod. 2013 Nov;28(11):3093-102. doi: 10.1093/humrep/det349. Epub 2013 Sep 5.
- Albrethsen J, Johannsen TH, Jorgensen N, Frederiksen H, Sennels HP, Jorgensen HL, Fahrenkrug J, Petersen JH, Linneberg A, Nordkap L, Bang AK, Andersson AM, Juul A. Evaluation of Serum Insulin-like Factor 3 Quantification by LC-MS/MS as a Biomarker of Leydig Cell Function. J Clin Endocrinol Metab. 2020 Jun 1;105(6):dgaa145. doi: 10.1210/clinem/dgaa145.
- Albrethsen J, Ljubicic ML, Juul A. Longitudinal Increases in Serum Insulin-like Factor 3 and Testosterone Determined by LC-MS/MS in Pubertal Danish Boys. J Clin Endocrinol Metab. 2020 Oct 1;105(10):dgaa496. doi: 10.1210/clinem/dgaa496.
- Bay K, Hartung S, Ivell R, Schumacher M, Jurgensen D, Jorgensen N, Holm M, Skakkebaek NE, Andersson AM. Insulin-like factor 3 serum levels in 135 normal men and 85 men with testicular disorders: relationship to the luteinizing hormone-testosterone axis. J Clin Endocrinol Metab. 2005 Jun;90(6):3410-8. doi: 10.1210/jc.2004-2257. Epub 2005 Mar 8.
- Anand-Ivell R, Wohlgemuth J, Haren MT, Hope PJ, Hatzinikolas G, Wittert G, Ivell R. Peripheral INSL3 concentrations decline with age in a large population of Australian men. Int J Androl. 2006 Dec;29(6):618-26. doi: 10.1111/j.1365-2605.2006.00714.x. Epub 2006 Oct 3.
- Ferlin A, Garolla A, Rigon F, Rasi Caldogno L, Lenzi A, Foresta C. Changes in serum insulin-like factor 3 during normal male puberty. J Clin Endocrinol Metab. 2006 Sep;91(9):3426-31. doi: 10.1210/jc.2006-0821. Epub 2006 Jun 27.
- Bay K, Andersson AM. Human testicular insulin-like factor 3: in relation to development, reproductive hormones and andrological disorders. Int J Androl. 2011 Apr;34(2):97-109. doi: 10.1111/j.1365-2605.2010.01074.x.
- Penny R, Olambiwonnu NO, Frasier SD. Episodic fluctuations of serum gonadotropins in pre- and post-pubertal girls and boys. J Clin Endocrinol Metab. 1977 Aug;45(2):307-11. doi: 10.1210/jcem-45-2-307.
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Estimado)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- INSL3GNRH
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Descrição do plano IPD
De-identified individual participant data (IPD) underlying the results of this study will be shared upon reasonable request to the Principal Investigator. The shared data will include clinical, auxological, biochemical, and instrumental parameters used for the analyses, provided in a completely anonymous format to protect participant privacy.
Prazo de Compartilhamento de IPD
Following the publication of the study results.
Critérios de acesso de compartilhamento IPD
Data will be shared upon reasonable request submitted to the Principal Investigator.
Tipo de informação de suporte de compartilhamento de IPD
- PROTOCOLO DE ESTUDO
- SEIVA
Informações sobre medicamentos e dispositivos, documentos de estudo
Estuda um medicamento regulamentado pela FDA dos EUA
Estuda um produto de dispositivo regulamentado pela FDA dos EUA
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .