Efficacy, Metabolism and BMD of the 3-month TP Compared to the 1-month TP in ICPP
- Conditions
- Central Precocious Puberty
- Interventions
- Registration Number
- NCT06487143
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 134
- 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 ≥ 0.6.
- 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.
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.).
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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:
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Known hypersensitivity to any investigational substance or related compounds.
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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].
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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).
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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.
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BMI ≥ 95th percentile (same age and gender).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 3-month triptorelin Triptorelin pamoate（15mg） Triptorelin pamoate is administered via intramuscular injection once every three months 1-month triptorelin Triptorelin acetate （3.75mg） Triptorelin acetate 3.75mg is administered via intramuscular injection once every four weeks.
- Primary Outcome Measures
Name Time Method The proportion of LH of ≤ 3 IU/L 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.
- Secondary Outcome Measures
Name Time Method Tanner stage Month 0, 3 ,6 and 12 after injection of triptorelin 3M and 1M Percentage of children with regression or no progression in Tanner staging. Pubertal stage was determined by an experienced pediatric endocrinologist according to the method proposed by Marshall and Tanner.
BA/CA Month 0, 6 and 12 after injection of triptorelin 3M and 1M Changes in bone age (BA) and the ratio of bone age to chronological age (BA/CA) compared to baseline. Bone age determination will be conducted using an X-ray imaging device to capture X-ray images of the hand and wrist. The BA will be interpreted using a standardized AI bone age assessment instrument (Yitu system).
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 Changes in baseline luteinizing hormone (LH) levels ,follicle-stimulating hormone (FSH), estradiol (E2), and testosterone (T) after treatment compared to baseline.Serum LH, FSH, estradiol and testosterone levels were measured by electroimmunochemiluminescence assays.
Uterine length (female)（mL) and testicular volume (male)(mL) Month 0, 3 ,6 and 12 after injection of triptorelin 3M and 1M Changes in uterine length and ovarian volume for girls, and testicular volume for boys. Pelvic ultrasound will be used to measure the uterine length and ovarian dimensions (length, width, and thickness). The ovarian volume will be calculated using the given formula.The Prader orchidometer will be used to measure the testicular volume before and after treatment.
Growth velocity (cm/y) Month 0, 3 ,6 and 12 after injection of triptorelin 3M and 1M Changes in growth velocity (GV) after treatment compared to baseline.Growth velocity (GV) is typically measured as the annual growth rate, which is the increase in height over a year.
PAH(cm) Month 0, 6 and 12 after injection of triptorelin 3M and 1M Predicted adult height (PAH) was calculated using the average tables from the Bayley-Pinneau method
Body composition Month 0 and 12 after injection of triptorelin 3M and 1M Comparison of body fat percentage after treatment to baseline using Dual-Energy X-ray Absorptiometry (DXA).
Bone Mineral Density Month 0 and 12 after injection of triptorelin 3M and 1M Comparison of the lowest T-score among the lumbar spine (L1-L4), total hip, and femoral neck after treatment to baseline using Dual-Energy X-ray Absorptiometry (DXA).
BMISDS Month 0, 6 and 12 after injection of triptorelin 3M and 1M Standard deviation scores (SDS) of body mass index (BMI) were calculated using the 2005 growth chart for Chinese children and adolescents aged 0-18 years.Changes in BMI SDS after Treatment Compared to Baseline
glucose metabolism Month 0, 6 and 12 after injection of triptorelin 3M and 1M Changes in Fasting Blood Glucose(mmol/L), Fasting Insulin（μU/mL), and HOMA-IR After Treatment Compared to Baseline.HOMA-IR was calculated by (Fasting Insulin(μU/mL)×Fasting Glucose(mmol/L)) minus 22.5.
lipid metabolism Month 0, 6 and 12 after injection of triptorelin 3M and 1M Changes in Total Cholesterol (TC)(mg/dL) , Low-Density Lipoprotein (LDL) (mg/dL) ,High-Density Lipoprotein (HDL)(mg/dL), Triglycerides (TG) (mg/dL)After Treatment Compared to Baseline.
Trial Locations
- Locations (1)
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
🇨🇳Guangzhou, Guangdong, China