Congenital Adrenal HyperplasiaPhase 1/2NCT00519818
Comparison of Two Forms of Hydrocortisone in Patients With Congenital Adrenal Hyperplasia
A Phase 1/2 study testing Chronocort and Cortef in people with Congenital Adrenal Hyperplasia and 21-Hydroxylase Deficiency, run by Neurocrine UK Limited at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 16 to 60 years
- Conditions the study is for
- Congenital Adrenal Hyperplasia, 21-Hydroxylase Deficiency, Adrenogenital Syndrome
- What is being tested?
- Chronocort and Cortef
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2007to May 2009
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 60 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: 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.
Read more
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.
Read the detailed description
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.
- Being tested
- Chronocort, Cortef
- Keywords
- Congenital Adrenal Hyperplasia, Hydrocortisone, Pharmacokinetic, Pharmacodynamic
- Medical subject headings
- Adrenal Hyperplasia, Congenital, Congenital adrenal hyperplasia due to 21 hydroxylase deficiency, Adrenogenital Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ChronocortDrug
Also called Hydrocortisone modified release tablet treatment
Chronocort 30 mg once daily nigh time dose for 28 +/- 3 days duration
CortefDrug
Also called Hydrocortisone immediate release tablet
Cortef 3 times daily(total dose 30 mg)for minimum of 7 days
| Study group | Role | What they receive |
|---|---|---|
| Cortef and Chronocort | Experimental | Cortef 3 times daily(total dose 30 mg)for minimum of 7 days followed by Chronocort 30 mg once daily nigh time dose for 28 +/- 3 days duration Receives: Drug: Chronocort; Drug: Cortef |
What is being measured
The primary outcome is the main question the study is designed to answer.
Chronocort vs. Cortef Cortisol Concentrations (AUC Over 24 Hours - Time Points 0,.5,1,1.5,2,3,4,5,6,7,8,10,10.5,11, 11.5,12,13,15,17,17.5,18,18.5,19,20,22,24 Post Dose).
Measured: Cortef after one week, Chronocort after one month
Secondary outcomes (1)
17 Hydroxyprogesterone at 08.00 Hours
Measured: Cortef after one week compared with Chronocort after one month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2007 (estimated)
- Study startAug 2007
- Primary completionMay 2009
- Study completionMay 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Congenital Adrenal HyperplasiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Neurocrine UK Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- National Institutes of Health Clinical Center (CC)
- Responsible party
- Sponsor
- Investigators
- Deborah Merck, MD, Principal investigator, National Institutes of Health (NIH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00519818
- Sponsor's protocol ID
- 070211
- Status last verified
- Apr 2022
- First submitted
- 22 Aug 2007
- Last updated
- 26 Apr 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Therrell BL. Newborn screening for congenital adrenal hyperplasia. Endocrinol Metab Clin North Am. 2001 Mar;30(1):15-30. doi: 10.1016/s0889-8529(08)70017-3.
PubMed 11344933Merke DP, Bornstein SR. Congenital adrenal hyperplasia. Lancet. 2005 Jun 18-24;365(9477):2125-36. doi: 10.1016/S0140-6736(05)66736-0.
PubMed 15964450Krieger DT, Allen W, Rizzo F, Krieger HP. Characterization of the normal temporal pattern of plasma corticosteroid levels. J Clin Endocrinol Metab. 1971 Feb;32(2):266-84. doi: 10.1210/jcem-32-2-266. No abstract available.
PubMed 4321505
Study at a glance
From the registry record, last updated by the sponsor on 26 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Open Label, Crossover Pharmacokinetic and Pharmacodynamic Study to Compare Chronocort Versus Cortef in Patients With CAH
- ClinicalTrials.gov ID
- NCT00519818
- Acronym / sponsor ID
- 070211
- Keywords
- Congenital Adrenal Hyperplasia, Hydrocortisone, Pharmacokinetic, Pharmacodynamic
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Neurocrine UK LimitedIndustry (pharma, biotech, devices)
- Collaborators
- National Institutes of Health Clinical Center (CC)
- Study start
- Aug 2007
- Primary completion
- May 2009 (actual)
- Study completion
- May 2009 (actual)
- First posted
- 23 Aug 2007 (estimated)
- Results
- Posted 27 Aug 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cortef and Chronocort | Experimental | Drug: Chronocort, Drug: CortefCortef 3 times daily(total dose 30 mg)for minimum of 7 days followed by Chronocort 30 mg once daily nigh time dose for 28 +/- 3 days duration |
Who may qualify
- Ages
- 16 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ChronocortAlso: Hydrocortisone modified release tablet treatmentChronocort 30 mg once daily nigh time dose for 28 +/- 3 days duration | Drug | Cortef and Chronocort |
| CortefAlso: Hydrocortisone immediate release tabletCortef 3 times daily(total dose 30 mg)for minimum of 7 days | Drug | Cortef and Chronocort |
Primary outcome
Chronocort vs. Cortef Cortisol Concentrations (AUC Over 24 Hours - Time Points 0,.5,1,1.5,2,3,4,5,6,7,8,10,10.5,11, 11.5,12,13,15,17,17.5,18,18.5,19,20,22,24 Post Dose).
Time frame: Cortef after one week, Chronocort after one month
1 secondary outcome
17 Hydroxyprogesterone at 08.00 Hours
Time frame: Cortef after one week compared with Chronocort after one month
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 11344933Therrell BL. Newborn screening for congenital adrenal hyperplasia. Endocrinol Metab Clin North Am. 2001 Mar;30(1):15-30. doi: 10.1016/s0889-8529(08)70017-3.
- Background: PubMed 15964450Merke DP, Bornstein SR. Congenital adrenal hyperplasia. Lancet. 2005 Jun 18-24;365(9477):2125-36. doi: 10.1016/S0140-6736(05)66736-0.
- Background: PubMed 4321505Krieger DT, Allen W, Rizzo F, Krieger HP. Characterization of the normal temporal pattern of plasma corticosteroid levels. J Clin Endocrinol Metab. 1971 Feb;32(2):266-84. doi: 10.1210/jcem-32-2-266. No abstract available.
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RecruitingObservational study
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RecruitingPhase 3
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RecruitingPhase 4
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Deborah Merck, MD principal investigator
National Institutes of Health (NIH)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Chronocort and Cortef in people with Congenital Adrenal Hyperplasia and 21-Hydroxylase Deficiency, run by Neurocrine UK Limited at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Aug 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Chronocort vs. Cortef Cortisol Concentrations (AUC Over 24 Hours - Time Points 0,.5,1,1.5,2,3,4,5,6,7,8,10,10.5,11, 11.5,12,13,15,17,17.5,18,18.5,19,20,22,24 Post Dose). (time frame: Cortef after one week, Chronocort after one month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00519818, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Apr 2022.