Comparison of Two Forms of Hydrocortisone in Patients With Congenital Adrenal Hyperplasia
| Status: | Completed |
|---|---|
| Conditions: | Endocrine, Hematology |
| Therapuetic Areas: | Endocrinology, Hematology |
| Healthy: | No |
| Age Range: | 16 - 60 |
| Updated: | 4/21/2016 |
| Start Date: | August 2007 |
| End Date: | May 2009 |
A Phase 2, Open Label, Crossover Pharmacokinetic and Pharmacodynamic Study to Compare Chronocort Versus Cortef in Patients With CAH
This study will test a new, extended release form of hydrocortisone called Chronocort in
patients with congenital adrenal hyperplasia (CAH). People with CAH do not make enough of
the adrenal hormones cortisol and aldosterone, and their adrenal glands make too much of the
sex hormone androgen. Medicines called glucocorticoids (hydrocortisone, dexamethasone and
prednisone) are currently used to treat CAH, but finding the best dose of these drugs that
effectively lowers androgens without causing undesirable side effects, such as weight gain
and slow growth rate in children, is often difficult to achieve.
Adolescents and adults with CAH due to 21-hydroxylase deficiency may be eligible for this
study. Children 16 years of age and older are eligible with confirmation by bone age that
they are no longer growing.
Participants undergo the following tests and procedures during two inpatient visits one
month apart at the NIH Clinical Center:
- Medical history and physical examination.
- Medications: Following 7 days of Cortef (standard drug treatment for CAH), patients
begin taking Chronocort on day 3 of hospitalization and continue the tablets once a day
for 1 month.
- Blood tests: A catheter (plastic tube) is inserted in a vein and left in place for
frequent blood draws in order to avoid repeated needlesticks. Blood is drawn for
chemistries, blood count, pregnancy test in women, and for serial tests (up to 26
samples in a 24-hour period) to measure hormone levels.
- 24-hour urine test.
- Height and weight measurements.
Between the two hospitalizations, patients are contacted by NIH weekly to check for possible
side effects from Chronocort. Two weeks after the first visit, patients also will have blood
drawn by their regular doctor or a local clinic. A few days before the second
hospitalization, patients undergo a 20-minute telephone questionnaire about energy level and
well being.
About 30 days after discharge from the second hospitalization, patients are followed up with
a telephone call to see how they are doing.
patients with congenital adrenal hyperplasia (CAH). People with CAH do not make enough of
the adrenal hormones cortisol and aldosterone, and their adrenal glands make too much of the
sex hormone androgen. Medicines called glucocorticoids (hydrocortisone, dexamethasone and
prednisone) are currently used to treat CAH, but finding the best dose of these drugs that
effectively lowers androgens without causing undesirable side effects, such as weight gain
and slow growth rate in children, is often difficult to achieve.
Adolescents and adults with CAH due to 21-hydroxylase deficiency may be eligible for this
study. Children 16 years of age and older are eligible with confirmation by bone age that
they are no longer growing.
Participants undergo the following tests and procedures during two inpatient visits one
month apart at the NIH Clinical Center:
- Medical history and physical examination.
- Medications: Following 7 days of Cortef (standard drug treatment for CAH), patients
begin taking Chronocort on day 3 of hospitalization and continue the tablets once a day
for 1 month.
- Blood tests: A catheter (plastic tube) is inserted in a vein and left in place for
frequent blood draws in order to avoid repeated needlesticks. Blood is drawn for
chemistries, blood count, pregnancy test in women, and for serial tests (up to 26
samples in a 24-hour period) to measure hormone levels.
- 24-hour urine test.
- Height and weight measurements.
Between the two hospitalizations, patients are contacted by NIH weekly to check for possible
side effects from Chronocort. Two weeks after the first visit, patients also will have blood
drawn by their regular doctor or a local clinic. A few days before the second
hospitalization, patients undergo a 20-minute telephone questionnaire about energy level and
well being.
About 30 days after discharge from the second hospitalization, patients are followed up with
a telephone call to see how they are doing.
Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a disease of the
adrenal cortex characterized by cortisol deficiency with or without aldosterone deficiency,
and androgen excess. The severe or classic form occurs in 1 in 15,000 births worldwide,
while the mild non-classic form is a common cause of hyperandrogenism. The discovery of
glucocorticoid therapy as a treatment for CAH occurred in the 1950's resulting in patients
with classic CAH surviving to live a normal lifespan. However, existing treatment is
suboptimal and many unresolved clinical problems exist. Standard hormone replacement often
fails to normalize the growth and development of children with CAH, and adults may
experience iatrogenic Cushing syndrome, hyperandrogenism, infertility or the development of
the metabolic syndrome. Chronocort, a newly-developed formulation of hydrocortisone, results
in a slow release of hydrocortisone that is designed to mimic the normal cortisol circadian
rhythm. This new medical strategy, physiologic cortisol replacement, offers the prospect of
an improved outcome of treatment. Chronocort has been safely given to healthy adult males in
pharmacokinetic studies. This first ever study in patients with CAH is a
pharmacokinetic/pharmacodynamic study comparing Chronocort to Cortef, the conventional
immediate-release form of hydrocortisone.
adrenal cortex characterized by cortisol deficiency with or without aldosterone deficiency,
and androgen excess. The severe or classic form occurs in 1 in 15,000 births worldwide,
while the mild non-classic form is a common cause of hyperandrogenism. The discovery of
glucocorticoid therapy as a treatment for CAH occurred in the 1950's resulting in patients
with classic CAH surviving to live a normal lifespan. However, existing treatment is
suboptimal and many unresolved clinical problems exist. Standard hormone replacement often
fails to normalize the growth and development of children with CAH, and adults may
experience iatrogenic Cushing syndrome, hyperandrogenism, infertility or the development of
the metabolic syndrome. Chronocort, a newly-developed formulation of hydrocortisone, results
in a slow release of hydrocortisone that is designed to mimic the normal cortisol circadian
rhythm. This new medical strategy, physiologic cortisol replacement, offers the prospect of
an improved outcome of treatment. Chronocort has been safely given to healthy adult males in
pharmacokinetic studies. This first ever study in patients with CAH is a
pharmacokinetic/pharmacodynamic study comparing Chronocort to Cortef, the conventional
immediate-release form of hydrocortisone.
- INCLUSION CRITERIA:
Satisfactory pre-trial screening
Provision of signed written informed consent and written assent from patients less than 18
years old, as applicable.
Good general health.
Females of childbearing potential must have a negative pregnancy test initially and at all
visits. Females who are engaging in sexual intercourse must be using medically acceptable
method of contraception.
EXCLUSION CRITERIA:
Co-morbid condition requiring daily administration of a medication that induces hepatic
enzymes or interferes with the metabolism of glucocorticoids.
Clinical or biochemical evidence of hepatic or renal disease. Creatinine above the normal
range or elevated liver function tests (Transaminases greater than 1.5 the upper limits of
normal).
Females who are pregnant or lactating.
Patients with any other significant medical or psychiatric conditions that in the opinion
of the Investigator would preclude participation in the trial.
Participation in another clinical trial of an investigational or licensed drug or device
within 3 months prior to inclusion in this study.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
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