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

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ClinicalTrials.gov Identifier: NCT00001521

Recruitment Status : Completed

First Posted : November 4, 1999

Last Update Posted : January 18, 2019

Sponsor:

Information provided by (Responsible Party):

National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )

Study Description

Brief 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>...

Condition or disease	Intervention/treatment	Phase
Congenital Adrenal Hyperplasia (CAH)	Drug: Flutamide Drug: Letrozole Drug: Hydrocortisone	Phase 2

Detailed 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.

Study Design


Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	62 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
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
Study Start Date :	February 2, 1996
Actual Primary Completion Date :	January 11, 2017
Actual Study Completion Date :	January 11, 2017

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: 17 alpha-hydroxylase/17,20-lyase deficiency 21-hydroxylase deficiency 3-beta-hydroxysteroid dehydrogenase deficiency Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency

Drug Information available for: Hydrocortisone Hydrocortisone sodium succinate Hydrocortisone cypionate Flutamide Hydrocortisone valerate Hydrocortisone probutate

Genetic and Rare Diseases Information Center resources: 21-hydroxylase Deficiency Congenital Adrenal Hyperplasia Hyperadrenalism

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Investigational 2 Flutamide, Aromatase inhibitor (testolactone/letrozole) and reduced hydrocortisone dose	Drug: Flutamide Non steroidal antiandrogen that prevents the action of androgens by blocking receptor sites in target tissue. It may also produce changes in testosterone and estradiol Drug: Hydrocortisone
Experimental: Investigational 1 Flutamide, Aromatase inhibitor (testolactone /letrozole) and reduced hydrocortisone dose	Drug: Letrozole Armomatase inhibitor. Drug: Hydrocortisone

Outcome Measures

Primary Outcome Measures :

Adult height [ Time Frame: at 13 fpr boys; 14 for girls ]
Principal outcome variable for long term study will be final adult height, body mass index, and bone mineral density.

Secondary Outcome Measures :

hormone levels (plasma, urine) [ Time Frame: at study conclusion and analysis ]
Predicted adult height (Bayley-Pinneau) [ Time Frame: at study conclusion and analysis ]
Weight velocity (SD units) [ Time Frame: at study conclusion and analysis ]
Growth velocity (SD units) [ Time Frame: at study conclusion and analysis ]

Eligibility Criteria

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Ages Eligible for Study:	2 Years to 18 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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).

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00001521

Locations


United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892

Sponsors and Collaborators

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

Investigators


Principal Investigator:	Deborah P Merke, M.D.	National Institutes of Health Clinical Center (CC)

More Information

Additional Information:

NIH Clinical Center Detailed Web Page This link exits the ClinicalTrials.gov site

Publications:

Urban MD, Lee PA, Migeon CJ. Adult height and fertility in men with congenital virilizing adrenal hyperplasia. N Engl J Med. 1978 Dec 21;299(25):1392-6.

New MI, Gertner JM, Speiser PW, del Balzo P. Growth and final height in classical and nonclassical 21-hydroxylase deficiency. Acta Paediatr Jpn. 1988;30 Suppl:79-88.

Klingensmith GJ, Garcia SC, Jones HW, Migeon CJ, Blizzard RM. Glucocorticoid treatment of girls with congenital adrenal hyperplasia: effects on height, sexual maturation, and fertility. J Pediatr. 1977 Jun;90(6):996-1004.


Responsible Party:	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:	NCT00001521 History of Changes
Other Study ID Numbers:	960033 96-CH-0033
First Posted:	November 4, 1999 Key Record Dates
Last Update Posted:	January 18, 2019
Last Verified:	December 18, 2018

Keywords provided by National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) ):


Congenital Adrenal Hyperplasia (CAH) Intervention Children

Additional relevant MeSH terms:


Hyperplasia Adrenal Hyperplasia, Congenital Adrenogenital Syndrome Adrenocortical Hyperfunction Pathologic Processes Disorders of Sex Development Urogenital Abnormalities Congenital Abnormalities Genetic Diseases, Inborn Steroid Metabolism, Inborn Errors Metabolism, Inborn Errors Metabolic Diseases Adrenal Gland Diseases Endocrine System Diseases Gonadal Disorders	Letrozole Flutamide Testolactone Aromatase Inhibitors Hydrocortisone 17-butyrate 21-propionate Hydrocortisone acetate Cortisol succinate Hydrocortisone Epinephrine Racepinephrine Epinephryl borate Antineoplastic Agents Steroid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action

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