Phase 3 N=62 Randomized Treatment

Three Drug Combination Therapy Versus Conventional Treatment of Children With Congenital Adrenal Hyperplasia

Congenital Adrenal Hyperplasia (CAH)

Bottom Line

View on ClinicalTrials.gov: NCT00001521 ↗

Enrolled (actual)

Serious AEs

19.7%

Results posted

Jun 2025

Primary outcome: Primary: Adult Height Relative to General Population — -0.34; -0.6 Standard Deviation Score (SDS) units

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: Fludrocortisone (Drug); Hydrocortisone (Drug); Letrozole (Drug); Flutamide (Drug); Testolactone (Drug)
Age: Pediatric, Adult · 2+ yrs
Sex: All
Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Primary completion: Apr 2024

Outcome Measures

Outcome	Result	p-value
PRIMARY Adult Height Relative to General Population	-0.34; -0.6	—
SECONDARY Adult Height Relative to Mid-parental Height	-0.45; -0.83; -0.89; -0.93; -0.02; -0.67	—
SECONDARY Predicted Adult Height	-2.0; -2.1; -0.46; -0.98	—
SECONDARY Predicted Adult Height Change	1.93; 1.10; -0.10; 0.14; 1.64; 1.20	—
SECONDARY Number of Years Bone Age Remained Unchanged	3.86; 2.78; 0.39; 0.70	—
SECONDARY Change in Body Mass Index (BMI)	0.12; 0.36; -0.06; -0.20	—
SECONDARY Body Mass Index (BMI)	1.07; 1.09; 0.79; 0.89	—
SECONDARY Average Annual Growth Velocity	-1.01; -0.34; 0.65; -0.29	—
SECONDARY Dose of Oral Hydrocortisone	14.7; 13.9; 7.6; 15.0; 16.4; 16.8	—
SECONDARY Average Daily Dose of Oral Hydrocortisone	10.1; 15.0; 9.5; 15.0; 9.1; 13.9	—
SECONDARY Percent of Visits With 17-hydroxyprogesterone in the Optimal Range (<1,200 ng/dL)	11.8; 35.9; 0; 28.6	—
SECONDARY Percent of Visits With Androstenedione in Normal Range	0; 45; 20.2; 50.0	—
SECONDARY Average Testosterone	86.3; 24.5; 336.0; 418.4; 42.3; 34.4	—
SECONDARY Number of Participants With Onset of Early Central Puberty	12; 9	—
SECONDARY Average Age at Menarche	14.7; 13.6	—
SECONDARY Number of Female Participants With Normal Menstrual Cyclicity at Final Visit	4; 7	—
SECONDARY Number of Participants With Insulin Resistance Based on Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) > 2.5	8; 12	—
SECONDARY Average (Median) Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)	2.42; 2.29	—
SECONDARY Number of Male Participants With Testicular Adrenal Rest Tumors (TART)	4; 3; 7; 7	—
SECONDARY Anterior Posterior Spine Bone Mineral Density (BMD) at Final Visit	-0.19; -0.25	—
SECONDARY Femoral Neck Bone Mineral Density (BMD) at Final Visit	-0.07; -0.32	—

Summary

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.

Eligibility Criteria

INCLUSION CRITERIA:

Subjects will be boys with bone ages 2 to 13 years and girls with bone ages 2 to 11 years with CAH due to classic 21-hydroxylase deficiency.

Subjects must either not yet have undergone pubertal activation of the hypothalamic-pituitary-gonadal axis, or, if pubertal activation has occurred, must be receiving a GnRH agonist to suppress secondary central precocious puberty.

Children with a bone age of 1 to 2 years may enroll in the protocol for optimization of conventional therapy, but will not be randomized to a study arm until the bone age reaches 2.

EXCLUSION CRITERIA

Children who have concurrent illnesses requiring glucocorticoid treatment (such as severe asthma), or requiring drugs that markedly alter hydrocortisone metabolism (such as anticonvulsants), and children who cannot be brought into reasonable control with conventional treatment (an unusual occurrence).

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00001521). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.