- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01771328
Continuous Subcutaneous Hydrocortisone Infusion in Congenital Adrenal Hyperplasia (CAH)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
CAH patients are treated with glucocorticoids and mineralocorticoids. Ideally, the glucocorticoid doses should be sufficient to suppress the elevated ACTH secretion, and hence attenuate the increase in androgen levels. Because of this, CAH patients use higher steroid doses than patients with autoimmune adrenal insufficiency (Addison's disease) and therefore are in higher risk of developing glucocorticoid side effects. The natural glucocorticoids, hydrocortisone (cortisol) or cortisone acetate, are preferred during childhood because of the growth suppressive effects of the longer acting synthetic glucocorticoids, prednisolone and dexamethasone. There is no consensus as to which type of glucocorticoid and which doses should be used for adult CAH patients. Glucocorticoids display a typical diurnal variation, which the current therapy does not restore, leading to both to over- or undertreatment. Some CAH patients experience symptoms that may be due to unphysiological glucocorticoid replacement therapy.
For selected CAH patients with poor response to conventional replacement therapy, or with problematic side effects such as impaired growth, weight gain, metabolic syndrome, and osteoporosis, continuous subcutaneous hydrocortisone infusion (CSHI) might become a treatment option. CSHI treatment would also be facilitated by the use of the small disposable pumps now developed for insulin treatment.
CSHI: Pharmacodynamics, Pharmacokinetics, and safety Hydrocortisone is identical to cortisol; the pharmacodynamics does not depend on mode of delivery. A hydrocortisone solution can be safely applied for three days in the insulin pump without major day-to-day variation. A daily dose of 10 mg/m2 body surface area/day restores normal levels of saliva cortisol in most patients. Thus, it is possible to mimic the physiological diurnal cortisol variation seen in healthy subjects.
The study will compare two glucocorticoid replacement modalities in randomised order within each patient. Prior to Baseline there will be a period of dose adjustment for pump treatment. Patients will be educated in groups, and dose adjustments will be co-ordinated with regular visits at the outpatient clinic/telephone consultation combined with laboratory analyses.
The patients will be assigned a participation number and randomised to any of two treatment sequences (A-B or B-A). Should the need for an extra glucocorticoid dose occur (intercurrent illness) during the study, the patients should administer their previous glucocorticoid replacement for safety reasons. Extra doses should be recorded in the patient diary. Treatment A is current treatment, i.e. glucocorticoid and mineralocorticoid replacement according to best clinical judgement. Treatment B is CSHI with the initial standard dose of 10mg/m2/24hrs. Body surface area will be calculated according to the nomogram from the formula of Du Bois and Du Bois.
After 7 days after initiating pump therapy the patient should be reassessed with blood dots (17-hydroxyprogesterone) and saliva cortisol and saliva 17-hydroxyprogesterone measurements in the morning (0800-0900) and in the evening (2300-2400). Based on results of this testing the dose will be changed at the discretion of the investigator. The further new testing should be done within 7-10 days.
When the final dose is established a 24h urine measurement, blood test in the morning (17-hydroxyprogesterone and cortisol) and a salivary sample full profile (full profile Hrs. 0800, 0930, 1100, 1230, 1700, 2100, 2400, 0300), will be done before entering the study. The dose adjustment period will be unlimited but will take minimally 4 weeks (aiming to obtain normal range levels of morning serum cortisol (160- 620 nmol/l), and 3-4 times increase in morning serum 17-hydroxyprogesterone (0,3-8,6 nmol/l for females, 0,9-6,6 nmo/l for males), and midnight (24:00) saliva cortisol (<2,8 nmol/l) and a circadian pattern as indicated in figure 1.
Afterwards it will 4 weeks wash out period before starting, wash out period between treatments modalities will take 2 months.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
-
Bergen, Norway, 5021
- Recruiting
- Haukeland Universitetssykehus, Department of Medicine
-
Contact:
- Kristian Løvås, MD, PhD
- Phone Number: +4755977996
- Email: kral@helse-bergen.no
-
Contact:
- Katerina Simunkova, MD, PhD
- Phone Number: +4755974603
- Email: katerina.simunkova@med.uib.no
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Principal Investigator:
- Kristian Løvås, MD, PhD
-
Sub-Investigator:
- Marianne Øksnes, MD
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Sub-Investigator:
- Ingrid Nermoen, MD
-
Sub-Investigator:
- Paal Methlie, MD
-
Sub-Investigator:
- Eystein S Husebye, prof., MD
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Principal Investigator:
- Katerina Simunkova, MD, PhD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- verified salt-wasting CAH and simple virilizing CAH, on single prednisone, or hydrocortisone therapy.
- In case of concomitant endocrine/autoimmune diseases these should be on stable treatment during the study period.
Exclusion Criteria:
- Patients with diabetes mellitus on insulin pump treatment will not be included in this study
- cardiovascular disease, active malignant disease and pregnancy, and pharmacological treatment with glucocorticoids or drugs that interfere with cortisol metabolism (antiepileptics, rifampicin, St. Johns wart).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: hydrocortisone
Treatment B ( Solu-Cortef) the initial standard dose of 10mg/m2/24hrs.
Hydrocortisone infusate will be given as Solu-Cortef Act-o-Vial 50mg/ml, produced by Pfizer.
Treatment will take 4 months.
|
Initial standard dose of 10mg/m2/24hrs administered by pump during the treatment period, it will take 4 months.
Body surface area will be calculated according to the nomogram from the formula of Du Bois and Du Bois.
Other Names:
|
Active Comparator: cortisone acetate
Treatment A (Cortisone tbl.) is current treatment, i.e. glucocorticoid and mineralocorticoid replacement according to best clinical judgement.
This treatment period will take 6 months.
|
Patients will take this tables two times during day according to best clinical practice of therapy of congenital adrenal hyperplasia.
Usually Cortisone 25 mg 1 tbl. in the morning and Cortisone 25 1/4 tbl. in the evening.
This period will take 6 months.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Androgen levels
Time Frame: 3 months
|
Androgen levels as parameters of adequate suppression of androgen production
|
3 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Steroid metabolism
Time Frame: 4 months
|
levels of ACTH
|
4 months
|
bone metabolism
Time Frame: 3 months
|
3 months
|
|
fasting glucose
Time Frame: 4 months
|
4 months
|
|
body mass index
Time Frame: 3 months
|
3 months
|
|
Dual-energy X-ray absorptiometry (DXA)
Time Frame: 6 months
|
body composition, bone mineral density
|
6 months
|
Subjective health status
Time Frame: 3 months
|
questionnaire
|
3 months
|
waist circumference
Time Frame: 3 month
|
cm
|
3 month
|
hip circumference
Time Frame: 3 months
|
cm
|
3 months
|
blood pressure
Time Frame: 3 months
|
3 months
|
|
fasting insulin
Time Frame: 3-4 months
|
3-4 months
|
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glycated haemoglobin (Hb1AC)
Time Frame: 4 months
|
4 months
|
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lipid levels
Time Frame: 4 months
|
4 months
|
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c-reactive protein
Time Frame: 4 months
|
4 months
|
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Steroid metabolism
Time Frame: 4 months
|
cortisol levels
|
4 months
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Kristian Løvås, MD, PhD, Haukeland University Hospital, Department of Medicine
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Metabolic Diseases
- Endocrine System Diseases
- Gonadal Disorders
- Disorders of Sex Development
- Urogenital Abnormalities
- Congenital Abnormalities
- Genetic Diseases, Inborn
- Metabolism, Inborn Errors
- Adrenal Gland Diseases
- Steroid Metabolism, Inborn Errors
- Hyperplasia
- Adrenal Hyperplasia, Congenital
- Adrenogenital Syndrome
- Adrenocortical Hyperfunction
- Anti-Inflammatory Agents
- Hydrocortisone
- Hydrocortisone hemisuccinate
- Cortisone
Other Study ID Numbers
- 2012/749
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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