The Effects of the 3-month Formulation of Triptorelin (TP) Compared to the 1-month Formulation on the Efficacy, Glucose and Lipid Metabolism, and Bone Mineral Density(BMD) in Idiopathic Central Precocious Puberty(ICPP)
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 134
- 试验地点
- 1
- 主要终点
- The proportion of LH of ≤ 3 IU/L
研究概览
简要总结
The primary objective of this study is to compare the efficacy of the 3-month formulation and 1-month formulation of triptorelin and to assess the short-term effects of the 3-month formulation of triptorelin on glucose and lipid metabolism, body composition, and bone density in Chinese ICPP patients.
详细描述
Idiopathic central precocious puberty (CPP) is an important treatable disease causing pubertal growth disorders. Gonadotropin-releasing hormone analogs (GnRHa) are the first-line drugs for treating idiopathic central precocious puberty (ICPP). Currently, the 1-month formulation (3.75mg) is the most widely used in China. The development of long-acting formulations will reduce the number of injections and treatment costs for children, as well as reduce the clinical visit burden. The 3-month formulation of Triptorelin Pamoate (15mg) was approved for use in central precocious puberty in March 2023. At present, there is only one publicly reported small-sample, single-arm clinical study in China, and there are no large-sample, real-world, concurrent controlled clinical study data on the efficacy and safety of the 3-month and 1-month formulations of triptorelin in the treatment of central precocious puberty. In currently reported safety events both domestically and internationally, there are no reports on the effects of the 3-month formulation of triptorelin on patients' glucose and lipid metabolism, body composition, and bone density. Our research team previously observed in a small-sample retrospective study of female patients with ICPP that after 1 year of treatment with the 3-month formulation of GnRHa (11.25mg leuprorelin), it effectively inhibited the hypothalamic-pituitary-gonadal axis and bone age progression, improved predicted adult height, and had no serious safety events. Therefore, based on our previous work, we plan to conduct a large-sample, real-world, concurrent controlled study to evaluate the gonadal axis suppression and predicted adult height benefits of the 3-month formulation of triptorelin compared to the 1-month formulation in patients with central precocious puberty (CPP). Additionally, we will assess the short-term effects of the 3-month formulation of triptorelin on glucose and lipid metabolism, body composition, and bone density in ICPP patients. The study results are expected to provide clinical evidence for the application of the 3-month formulation in the treatment of central precocious puberty in China.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 10 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Early appearance of secondary sexual characteristics, specifically breast development in girls before 8 years old or menarche before 10 years old, and testicular enlargement in boys before 9 years old.
- •Gonadal enlargement: pelvic ultrasound shows that girls have at least one ovarian follicle with a diameter >4mm, and breast development is at least at Tanner stage II; boys have a testicular volume ≥ 4 ml (measured with Prader orchidometer).
- •GnRH stimulation test: LH peak value ≥ 5 IU/L (chemiluminescence method), with an LH peak/FSH peak ratio ≥ 0.
- •Bone age (BA) exceeds chronological age (CA) by 1 year or more (based on bone age assessment during the screening period at this center).
- •Accelerated linear growth, with an annual growth rate higher than that of healthy children of the same age.
- •No prior treatment with gonadotropin-releasing hormone agonists.
- •Body weight of at least 20 kg.
排除标准
- •1.Target Diseases:
- •Secondary central precocious puberty: This includes central nervous system abnormalities (tumors or space-occupying lesions, acquired injuries, congenital developmental abnormalities, etc.) and other diseases (congenital adrenal hyperplasia, familial male-limited precocious puberty, McCune-Albright syndrome, etc.).
- •Slow-progressing central precocious puberty: Some children show signs of sexual development before the defined age (7-8 years), but the progression of sexual development and bone age is slow, and linear growth remains within the corresponding percentiles.
- •2.Treatment History, Medical History, and Concomitant Medical Conditions:
- •Known hypersensitivity to any investigational substance or related compounds.
- •Any chronic disease or treatment deemed by the investigator to potentially interfere with growth or other study endpoints [including but not limited to: long-term glucocorticoid use (excluding short-term topical use), renal failure, diabetes, moderate to severe scoliosis].
- •Girls with a bone age over 12.5 years or menarche ≥ 1 year; boys with a bone age over 14 years (based on bone age assessment during the screening period at this center).
- •Congenital long QT syndrome/12-lead ECG at screening showing QTc ≥ 500 ms corrected by Bazett's formula, excluding other factors causing prolonged QT interval on ECG/12-lead ECG at screening showing QTc between 480 and 499 ms accompanied by unexplained syncope, with no other factors causing prolonged QT interval and no pathogenic mutations.
- •BMI ≥ 95th percentile (same age and gender).
研究组 & 干预措施
3-month triptorelin
Triptorelin pamoate is administered via intramuscular injection once every three months
干预措施: Triptorelin pamoate（15mg） (Drug)
1-month triptorelin
Triptorelin acetate 3.75mg is administered via intramuscular injection once every four weeks.
干预措施: Triptorelin acetate （3.75mg） (Drug)
结局指标
主要结局
The proportion of LH of ≤ 3 IU/L
时间窗: 3 months after injection of 3-month TP and 1-month TP
In the GnRHa stimulation test, triptorelin is administered intravenously at a dose of 0.1 mg/m² (with a maximum dose of 0.1 mg). Blood samples are collected 60 minutes after administration to measure luteinizing hormone (LH) levels.Serum LH levels were measured by electroimmunochemiluminescence assays.
次要结局
- Tanner stage(Month 0, 3 ,6 and 12 after injection of triptorelin 3M and 1M)
- BA/CA(Month 0, 6 and 12 after injection of triptorelin 3M and 1M)
- Basal LH（ IU/L),Basal FSH（IU/L), Estradiol (female) (pg/mL)and testosterone (male)(pg/mL)(Month 0, 3 ,6 and 12 after injection of triptorelin 3M and 1M)
- glucose metabolism(Month 0, 6 and 12 after injection of triptorelin 3M and 1M)
- lipid metabolism(Month 0, 6 and 12 after injection of triptorelin 3M and 1M)
- Uterine length (female)（mL) and testicular volume (male)(mL)(Month 0, 3 ,6 and 12 after injection of triptorelin 3M and 1M)
- Growth velocity (cm/y)(Month 0, 3 ,6 and 12 after injection of triptorelin 3M and 1M)
- PAH(cm)(Month 0, 6 and 12 after injection of triptorelin 3M and 1M)
- Body composition(Month 0 and 12 after injection of triptorelin 3M and 1M)
- Bone Mineral Density(Month 0 and 12 after injection of triptorelin 3M and 1M)
- BMISDS(Month 0, 6 and 12 after injection of triptorelin 3M and 1M)
研究者
Zhe Meng,MD
Associate chief physician
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University