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

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

66 participants

Study Classification

INTERVENTIONAL

Study Start Date

1995-06-08

Study Completion Date

2024-04-01

Brief Summary

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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.

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Detailed Description

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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.

Conditions

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Congenital Adrenal Hyperplasia (CAH)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Fludrocortisone

Intervention Type DRUG

Mineralocorticoid needed to replace aldosterone deficiency. Patients will continue to receive an optimal fludrocortisone dose

Hydrocortisone

Intervention Type DRUG

Glucocorticoid needed to replace cortisol deficiency. Reduced hydrocortisone dose might normalize the growth and adult stature of children with congenital adrenal hyperplasia

Letrozole

Intervention Type DRUG

Aromatase inhibitors work by inhibiting the action of the enzyme aromatase, which converts androgens into estrogens by a process called aromatization.

Flutamide

Intervention Type DRUG

Non steroidal anti-androgen that prevents the action of androgens by blocking receptor sites in target tissue. It may also produce changes in testosterone and estradiol

Testolactone

Intervention Type DRUG

Aromatase inhibitors work by inhibiting the action of the enzyme aromatase, which converts androgens into estrogens by a process called aromatization.

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.

Group Type EXPERIMENTAL

Fludrocortisone

Intervention Type DRUG

Mineralocorticoid needed to replace aldosterone deficiency. Patients will continue to receive an optimal fludrocortisone dose

Hydrocortisone

Intervention Type DRUG

Glucocorticoid needed to replace cortisol deficiency. Reduced hydrocortisone dose might normalize the growth and adult stature of children with congenital adrenal hyperplasia

Interventions

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Fludrocortisone

Mineralocorticoid needed to replace aldosterone deficiency. Patients will continue to receive an optimal fludrocortisone dose

Intervention Type DRUG

Hydrocortisone

Glucocorticoid needed to replace cortisol deficiency. Reduced hydrocortisone dose might normalize the growth and adult stature of children with congenital adrenal hyperplasia

Intervention Type DRUG

Letrozole

Aromatase inhibitors work by inhibiting the action of the enzyme aromatase, which converts androgens into estrogens by a process called aromatization.

Intervention Type DRUG

Flutamide

Non steroidal anti-androgen that prevents the action of androgens by blocking receptor sites in target tissue. It may also produce changes in testosterone and estradiol

Intervention Type DRUG

Testolactone

Aromatase inhibitors work by inhibiting the action of the enzyme aromatase, which converts androgens into estrogens by a process called aromatization.

Intervention Type DRUG

Eligibility Criteria

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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).

Minimum Eligible Age

2 Years

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No