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

Congenital Adrenal Hyperplasia (CAH) Clinical Trial

Official title:

An Open, Randomized, Long-Term Clinical Trial of Flutamide, Testolactone, and Reduced Hydrocortisone Dose vs. Conventional Treatment of Children With Congenital Adrenal Hyperplasia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00001521
• Other study ID #: 960033
• Secondary ID: 96-CH-0033
• Status: Completed
• Phase: Phase 4
• Start date: June 8, 1995
• Est. completion date: April 1, 2024

Study information

• Verified date: May 8, 2024
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 six months after their first menstrual period.

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, body mass index, and bone density. <TAB>...

Description:

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 measures will be adult height, body mass index, and bone density.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: April 1, 2024
• Est. primary completion date: April 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 18 Years

Eligibility

• INCLUSION CRITERIA:

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

Subjects must either not yet have undergone pubertal activation of the hypothalamic-pituitary-gonadal axis, or, if pubertal activation has occurred, must be receiving an LHRH 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).

Related Conditions & MeSH terms

• Adrenal Hyperplasia, Congenital
• Adrenocortical Hyperfunction
• Adrenogenital Syndrome
• Congenital Adrenal Hyperplasia (CAH)
• Hyperplasia

Intervention

Drug:
• Fludrocortisone
Since hydrocortisone dosage will be reduced , some patients may develop symptoms or signs of adrenal insufficiency. Patients will continue to receive an optimal fludrocortisone dose
• Hydrocortisone
reduced hydrocortisone dose can normalize the growth and adult stature of children with congenital adrenal hyperplasia
• Letrozole
Aromatase inhibitors work by inhibiting the action of the enzyme aromatase, which converts androgens into estrogens by a process called aromatization.
• 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

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adult height	The primary outcome variable is adult height which will be expressed in SD units relative to the normal population.	at 13 for boys; 14 for girls
Secondary	hormone levels (plasma, urine)	hormone levels	at study conclusion and analysis
Secondary	Predicted adult height (Bayley-Pinneau)	adult height	at study conclusion and analysis
Secondary	Weight velocity (SD units)	body mass index, and bone density	at study conclusion and analysis
Secondary	Growth velocity (SD units)	adult height, body mass index, and bone density	at study conclusion and analysis

External Links

•   NIH Clinical Center Detailed Web Page