Addison Disease Clinical Trial
Official title:
Use of Liquorice and Grapefruit in Patients With Addison's Disease
Addison's disease is a rare disease, wherein the adrenals can not produce sufficient steroid hormones (cortisol and aldosterone). Patients with Addison's disease report impaired subjective health status, and they have increased all-cause mortality. Conventional therapy is by oral replacement of glucocorticoid and mineralocorticoid hormones, but this strategy imperfectly mimic the diurnal cortisol variations, and render the patients both over- and under-treated. Anecdotally, some patients with adrenal insufficiency may benefit from the use of various nutritional compounds. We hypothesised that liquorice and grapefruit altered the metabolism and absorption of cortisone acetate.
Status | Completed |
Enrollment | 17 |
Est. completion date | January 2009 |
Est. primary completion date | January 2009 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years to 80 Years |
Eligibility |
Inclusion Criteria: - Verified diagnosis of adrenal insufficiency (Addison's disease) - Stable cortisone acetate replacement therapy - Written informed consent Exclusion Criteria: - Malignant disease - Pharmacological treatment with other glucocorticoids - Pregnancy - Current minor disease (ie the flu) - Major disease or accident requiring hospitalization the last three months - Use of grapefruit juice or liquorice the last two weeks before study start - Blood pressure above 150mmHg systolic or 90 mmHg diastolic. |
Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Supportive Care
Country | Name | City | State |
---|---|---|---|
Norway | Haukeland University Hospital, Helse-Bergen HF | Bergen |
Lead Sponsor | Collaborator |
---|---|
Haukeland University Hospital |
Norway,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | AUC Serum Cortisol - Levels of cortisol in serum during the first 2.6 hours after oral administration of cortisone acetate. | The area under the curve (AUC) of cortisol is calculated based on serum time-series sampling (every 20 minutes for 2.6 h after oral administration of cortisone acetate). The AUCs obtained during liquorice and grapefruit juice intakes are compared to the baseline assessment (without these nutritional compounds). All other pharmacokinetic properties (primary and secondary outcome measures) are compared analogously. | Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start. | No |
Secondary | Serum Cortisol levels at the end of time-series sampling (t=160min) | At the end of time series sampling (160 minutes after orally administered cortisone acetate) on all three assessments | Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start. | No |
Secondary | Serum Cortisone levels at the end of time-series sampling (t=160min) | At the end of time series sampling (160 minutes after orally administered cortisone acetate) on all three assessments | Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start. | No |
Secondary | Saliva Cortisol levels at the end of time-series sampling (t=160min) | At the end of time series sampling (160 minutes after orally administered cortisone acetate) on all three assessments | Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start. | No |
Secondary | Saliva Cortisone levels at the end of time-series sampling (t=160min) | At the end of time series sampling (160 minutes after orally administered cortisone acetate) on all three assessments | Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start. | No |
Secondary | Time of maximum concentration of serum Cortisol | Based on time-series sampling at each of the three assessments | Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start. | No |
Secondary | Time of maximum concentration of serum Cortisone | Based on time-series sampling at each of the three assessments | Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start. | No |
Secondary | Time of maximum concentration of Saliva Cortisol | Based on time-series sampling at each of the three assessments | Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start. | No |
Secondary | Time of maximum concentration of Saliva Cortisone | Based on time-series sampling at each of the three assessments | Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start. | No |
Secondary | Half life of serum cortisol | Based on time-series sampling at each of the three assessments | Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start. | No |
Secondary | Half life of serum cortisone | Based on time-series sampling at each of the three assessments | Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start. | No |
Secondary | Urinary aTHF/THF-ratio | Measured in 24h urine obtained at the three assessments. aTHF = allo-tetrahydrocortisol, THF = tetrahydrocortisol |
Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start. | No |
Secondary | AUC Serum Cortisone | Similar to primary outcome Serum AUC Cortisol | Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start. | No |
Secondary | Urine total metabolites (Urinary cortisol+cortisone+6OHF+aTHF+THF+THE) | 24-hour urine collected on each of the three assessments aTHF = allo-tetrahydrocortisol, THF = tetrahydrocortisol, THE = tetrahydrocortisone, 6OHF = 6beta-hydroxycortisol |
Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start. | No |
Secondary | Urinary ratio (aTHF+THF)/THE | Assessed in 24h urine obtained at the three assessments (baseline, after liquorice and after grapefruit juice). It is an index of 5-reductase activity. 24-hour urine collected on each of the three assessments aTHF = allo-tetrahydrocortisol, THF = tetrahydrocortisol, THE = tetrahydrocortisone |
Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start. | No |
Secondary | Urinary Ratio Cortisol/6beta-OH-Cortisol | Assess the enzymatic activity of CYP3A4 by the index urinary cortisol/6beta-oh cortisol ratio obtained at the three assessments (baseline, after liquorice and after grapefruit juice. 6OHF = 6beta-hydroxycortisol |
Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start. | No |
Secondary | Urine total metabolites (Urinary cortisol+cortisone+6OHF+aTHF+THF+THE) | 24-hour urine collected on each of the three assessments 24-hour urine collected on each of the three assessments aTHF = allo-tetrahydrocortisol, THF = tetrahydrocortisol, THE = tetrahydrocortisone, 6OHF = 6beta-hydroxycortisol |
Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start. | No |
Secondary | AUC Saliva cortisone | Similar to primary outcome Saliva AUC Cortisol, but for cortisone. | Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start. | No |
Secondary | AUC Serum Cortisone | Similar to primary outcome Serum AUC Cortisol, but for cortisone. | Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start. | No |
Secondary | AUC Saliva Cortisol | Similar to AUC Serum Cortisol, but measurements are on saliva. | Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start. | No |
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