Adrenal Hyperplasia, Congenital
Conditions
Brief summary
The purpose of this study is to determine if dexamethasone given at night is a more effective treatment for congenital adrenal hyperplasia in young children than standard three times per day hydrocortisone. Our hypothesis is that nocturnal dexamethasone will lead to more efficient suppression of the hypothalamic-pituitary-adrenal axis. We performed a cross-over trial comparing hormonal control during two 24-hour hospitalizations, one on hydrocortisone and one on nocturnal dexamethasone.
Detailed description
This is a Phase II clinical trial, intended to estimate the effect of instituting Dexamethasone therapy in comparison to prior standard therapy. Each subject provides his own baseline data. There is no control group. Patients with CAH who meet inclusion criteria will be admitted to the clinical research center for two 24 hour hospitalizations. Adrenal hormone profiles will be measured during each hospitalization. The patient will take his or her baseline hydrocortisone regimen during one hospitalization and a new regimen consisting of a single daily nocturnal dose of Dexamethasone during the second hospitalization.
Interventions
DRUGdexamethasone
Dexamethasone will be given at a dose that equals 1/50 of the total daily hydrocortisone dose of the patient. It will be given in solution form at 10 PM for 3 days.
DRUGHydrocortisone
Subjects were given their baseline hydrocortisone regimen which was three times daily for 4 of the subjects and twice daily for one subject. Doses were given at 8 AM, 2 PM, and 8 PM. The 2 PM time point was skipped for the subject who received hydrocortisone twice daily. Doses ranged from 6.9 to 18.5 milligrams per meter squared per day and were based on each individual's baseline regimen.
Sponsors
Boston Children's Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 9 Years
Healthy volunteers
No
Inclusion criteria
* Classic salt-wasting 21-hydroxylase deficient congenital adrenal hyperplasia * Pre-pubertal children with bone ages below 8 years
Exclusion criteria
* Age less than 2 years * Patients with additional medical conditions necessitating glucocorticoid therapy. * Patients on phenytoin, barbiturates, and rifampin as these medications accelerate the metabolism of glucocorticoids. * Patients on ketoconazole as this medication increases the bioavailability of glucocorticoids.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Difference in the Mean Log Transformed Area Under the Curve of 17-hydroxyprogesterone Between Regimens | 23 hours | Each subject was admitted for 2 24 hour hospitalizations, one on hydrocortisone and one on dexamethasone. Due to the timing of blood draws, the serum hormonal profile was only measured for 23 hours. The primary outcome was the Percent Difference in the Mean log transformed Area under the curve of 17-hydroxyprogesterone between the two regimens. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from the Endocrine Clinic at Children's Hospital Boston from April through November 2008.
Pre-assignment details
This was a cross over study. All subjects were admitted on their baseline hydrocortisone regimen for a 24 hour hospital admission. They then had a second hospital admission within 8 weeks while being administered the dexamethasone therapy.
Participants by arm
| Arm | Count |
|---|---|
| Experimental Group These subjects were admitted twice, once while on baseline hydrocortisone and once on dexamethasone. | 5 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Dexamethasone Admission | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Experimental Group |
|---|---|
| Age, Categorical <=18 years | 5 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Region of Enrollment United States | 5 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 5 | 0 / 5 |
| serious Total, serious adverse events | 0 / 5 | 0 / 5 |
Outcome results
Primary
Percent Difference in the Mean Log Transformed Area Under the Curve of 17-hydroxyprogesterone Between Regimens
Each subject was admitted for 2 24 hour hospitalizations, one on hydrocortisone and one on dexamethasone. Due to the timing of blood draws, the serum hormonal profile was only measured for 23 hours. The primary outcome was the Percent Difference in the Mean log transformed Area under the curve of 17-hydroxyprogesterone between the two regimens.
Time frame: 23 hours
Population: Only four participants completed both the hydrocortisone and dexamethasone admissions.
| Arm | Measure | Value (LOG_MEAN) | Dispersion |
|---|---|---|---|
| Dexamethasone Admission | Percent Difference in the Mean Log Transformed Area Under the Curve of 17-hydroxyprogesterone Between Regimens | 3.16 Log Mean Area Under the Curve | Standard Deviation 0.93 |
| Hydrocortisone Admission | Percent Difference in the Mean Log Transformed Area Under the Curve of 17-hydroxyprogesterone Between Regimens | 3.91 Log Mean Area Under the Curve | Standard Deviation 0.66 |
Comparison: A t-test was performed comparing the mean long transformed area under the curve of 17-hydroxyprogesterone between the dexamethasone and hydrocortisone arms. The percent difference in mean log AUC was calculated as:~(Mean log AUC on dexamethasone - Mean log AUC on hydrocortisone)/Mean log AUC on hydrocortisonep-value: 0.09t-test, 2 sided