An Open, Randomized, Long-Term Clinical Trial of Flutamide, Testolactone, and Reduced Hydrocortisone Dose vs. Conventional Treatment of Children With Congenital Adrenal Hyperplasia
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 66
- 试验地点
- 1
- 主要终点
- Adult Height Relative to General Population
研究概览
简要总结
This study was developed to determine if a combination of four drugs (flutamide, testolactone, reduced hydrocortisone dose, and fludrocortisone) can normalize growth in children with congenital adrenal hyperplasia.
The study will take 60 children, boys and girls, and divide them into 2 groups based on the medications given. Group one will receive the new four-drug combination. Group two will receive the standard treatment for congenital adrenal hyperplasia (hydrocortisone and fludrocortisone).
The boys in group one will take the medication until the age of 14 at which time they will stop taking the four-drug combination and begin receiving the standard treatment for congenital adrenal hyperplasia. Girls in group one will take the four-drug combination until the age of 13, at which time they will stop and begin receiving the standard treatment for congenital adrenal hyperplasia plus flutamide. Flutamide will be given to the girls until two years after their first menstrual period or until adult height.
All of the children will be followed until they reach their final adult height. The effectiveness of the treatment will be determined by measuring the patient's adult height.
详细描述
To test the hypothesis that the regimen of flutamide (an antiandrogen), testolactone or letrozole (an inhibitor of androgen-to-estrogen conversion), and reduced hydrocortisone dose can normalize the growth and adult stature of children with congenital adrenal hyperplasia, and can avoid the complications of supraphysiologic glucocorticoid dosage, 60 children with this disorder will be randomized to receive either the above regimen or conventional treatment until they have reached age 13 years in a girl or age 14 in a boy. After these ages boys will receive the conventional treatment and girls will receive conventional treatment plus flutamide. In girls, flutamide will be continued until 6 months after menarche. All children will be followed until they have attained final adult height. The principal outcome measure will be adult height.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Investigational therapy
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls were randomized to receive antiandrogen (flutamide 10mg/kg/day orally), aromatase inhibitor (testolactone - 20mg/ kg/day orally OR letrozole - 1.5mg/m^2 body surface area orally), low-dose hydrocortisone (6-8 mg/m^2/day orally), and fludrocortisone (100-200 mcg/day, depending on lab evaluation, orally). Participants received the four-drug regimen until the age of 13 in the girls and 14 in the boys and then were switched to standard therapy. Female participants on investigational drugs were continued on flutamide until attainment of final adult height or two years post menarche. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
干预措施: Fludrocortisone (Drug)
Investigational therapy
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls were randomized to receive antiandrogen (flutamide 10mg/kg/day orally), aromatase inhibitor (testolactone - 20mg/ kg/day orally OR letrozole - 1.5mg/m^2 body surface area orally), low-dose hydrocortisone (6-8 mg/m^2/day orally), and fludrocortisone (100-200 mcg/day, depending on lab evaluation, orally). Participants received the four-drug regimen until the age of 13 in the girls and 14 in the boys and then were switched to standard therapy. Female participants on investigational drugs were continued on flutamide until attainment of final adult height or two years post menarche. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
干预措施: Hydrocortisone (Drug)
Investigational therapy
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls were randomized to receive antiandrogen (flutamide 10mg/kg/day orally), aromatase inhibitor (testolactone - 20mg/ kg/day orally OR letrozole - 1.5mg/m^2 body surface area orally), low-dose hydrocortisone (6-8 mg/m^2/day orally), and fludrocortisone (100-200 mcg/day, depending on lab evaluation, orally). Participants received the four-drug regimen until the age of 13 in the girls and 14 in the boys and then were switched to standard therapy. Female participants on investigational drugs were continued on flutamide until attainment of final adult height or two years post menarche. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
干预措施: Letrozole (Drug)
Investigational therapy
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls were randomized to receive antiandrogen (flutamide 10mg/kg/day orally), aromatase inhibitor (testolactone - 20mg/ kg/day orally OR letrozole - 1.5mg/m^2 body surface area orally), low-dose hydrocortisone (6-8 mg/m^2/day orally), and fludrocortisone (100-200 mcg/day, depending on lab evaluation, orally). Participants received the four-drug regimen until the age of 13 in the girls and 14 in the boys and then were switched to standard therapy. Female participants on investigational drugs were continued on flutamide until attainment of final adult height or two years post menarche. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
干预措施: Flutamide (Drug)
Investigational therapy
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls were randomized to receive antiandrogen (flutamide 10mg/kg/day orally), aromatase inhibitor (testolactone - 20mg/ kg/day orally OR letrozole - 1.5mg/m^2 body surface area orally), low-dose hydrocortisone (6-8 mg/m^2/day orally), and fludrocortisone (100-200 mcg/day, depending on lab evaluation, orally). Participants received the four-drug regimen until the age of 13 in the girls and 14 in the boys and then were switched to standard therapy. Female participants on investigational drugs were continued on flutamide until attainment of final adult height or two years post menarche. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
干预措施: Testolactone (Drug)
Standard therapy
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls received standard therapy/conventional treatment (with hydrocortisone and fludrocortisone). Participants received hydrocortisone approximately 10-15 mg/m^2/day orally, not exceeding 25mg/m^2/day, and fludrocortisone 100-200 mcg/day orally depending on lab evaluation. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
干预措施: Fludrocortisone (Drug)
Standard therapy
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls received standard therapy/conventional treatment (with hydrocortisone and fludrocortisone). Participants received hydrocortisone approximately 10-15 mg/m^2/day orally, not exceeding 25mg/m^2/day, and fludrocortisone 100-200 mcg/day orally depending on lab evaluation. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
干预措施: Hydrocortisone (Drug)
结局指标
主要结局
Adult Height Relative to General Population
时间窗: Followed to attainment of adult height, average of 11 years from date of randomization
Adult height expressed in standard deviation score (SDS) units relative to the general population, with attainment of adult height defined as incremental growth \< 1.5 cm over 12 months. Adult height SDS was based on National Health and Nutrition Examination Survey (Centers for Disease Control and Prevention, National Center for Health Statistics) data at 20 years old.
次要结局
- Adult Height Relative to Mid-parental Height(Followed to attainment of adult height, average of 11 years from date of randomization)
- Predicted Adult Height(At date of randomization and at pubertal onset (average of seven years from date of randomization))
- Predicted Adult Height Change(From date of randomization to pubertal onset visit (which on average was seven years), pubertal onset to final visit (average was 4 years), and date of randomization to final visit (average of 11 years))
- Change in Body Mass Index (BMI)(From date of randomization to pubertal onset visit (which on average was seven years) and pubertal onset to final visit (average was 4 years))
- Number of Years Bone Age Remained Unchanged(From date of randomization to pubertal onset visit (which on average was seven years) and pubertal onset to final visit (average was 4 years))
- Body Mass Index (BMI)(Pubertal onset visit (average of seven years from date of randomization) and at final visit (average of 11 years from date of randomization))
- Average Annual Growth Velocity(From date of randomization to pubertal onset visit (which on average was seven years) and pubertal onset to final visit (average was 4 years))
- Dose of Oral Hydrocortisone(At date of randomization, pubertal onset (average of seven years from date of randomization), and at final visit (average of 11 years from date of randomization))
- Average Testosterone(From date of randomization to pubertal onset visit (which on average was seven years) and pubertal onset to final visit (average was 4 years))
- Average Daily Dose of Oral Hydrocortisone(From date of randomization to pubertal onset visit (which on average was seven years), pubertal onset to final visit (average was 4 years), and date of randomization to final visit (average of 11 years))
- Percent of Visits With 17-hydroxyprogesterone in the Optimal Range (<1,200 ng/dL)(From date of randomization to pubertal onset visit (which on average was seven years) and pubertal onset to final visit (average was 4 years))
- Average Age at Menarche(Followed from date of randomization to onset of menarche)
- Percent of Visits With Androstenedione in Normal Range(From date of randomization to pubertal onset visit (which on average was seven years) and pubertal onset to final visit (average was 4 years))
- Number of Male Participants With Testicular Adrenal Rest Tumors (TART)(Pubertal onset visit (average of seven years from date of randomization) and at final visit (average of 11 years from date of randomization))
- Number of Participants With Onset of Early Central Puberty(Measured from date of randomization to onset of early central puberty)
- Number of Female Participants With Normal Menstrual Cyclicity at Final Visit(Measured at single time point at final visit, average of 11 years from date of randomization)
- Number of Participants With Insulin Resistance Based on Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) > 2.5(Final visit, average of 11 years from date of randomization)
- Average (Median) Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)(Measured at single time point at final visit, average of 11 years from date of randomization)
- Anterior Posterior Spine Bone Mineral Density (BMD) at Final Visit(Final visit, average of 11 years from date of randomization)
- Femoral Neck Bone Mineral Density (BMD) at Final Visit(Final visit, average of 11 years from date of randomization)