A Study of Markers of Glucocorticoid Effects in Patients With Addisons Disease (DOSCORT)
Study Details
Study Description
Brief Summary
DOSCORT is a 2-dose, cross-over study primarily aiming to identify and validate novel biological markers (biomarkers) of glucocorticoid effect in the human body. Patients with Addison´s disease, primary adrenal insufficiency, with life-long glucocorticoid replacement therapy will undergo 2 treatment periods where their usual hydrocortisone treatment will be replaced with betamethasone in physiological and supra physiological doses. Blood, saliva, urine, health related Quality-of-life self-assessment forms, measurements of physical activity and sleep quality will be collected from both treatment periods.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: betamethasone - physiological dose Replacing participants hydrocortisone with a daily dose of betamethasone in an estimated physiological dose during one treatment period. |
Drug: Betamethasone
A cross-over study where patients with Addison´s disease will undergo two treatment periods where their usual hydrocortisone replacement therapy will be replaced by the glucocorticoid betamethasone in physiological and supra physiological doses. A wash-out period of 2-5 weeks in-between the treatment periods will be carried out where participants intake their usual hydrocortisone replacement therapy.
|
| Active Comparator: betamethasone - supra physiological dose Replacing participants hydrocortisone with a daily dose of betamethasone in an estimated supra physiological dose during one treatment period. |
Drug: Betamethasone
A cross-over study where patients with Addison´s disease will undergo two treatment periods where their usual hydrocortisone replacement therapy will be replaced by the glucocorticoid betamethasone in physiological and supra physiological doses. A wash-out period of 2-5 weeks in-between the treatment periods will be carried out where participants intake their usual hydrocortisone replacement therapy.
|
Outcome Measures
Primary Outcome Measures
- Protein profile changes between physiological and supra physiological doses of betamethasone. [Changes in proteome (g/dl or umol/l) during 7 days of treatment with two different doses of betamethasone]
By using mas spectrometry, protein profile changes in blood, urine and saliva will be identified at four timepoints: after 3 hours and after 7 days during treatment with betamethasone in a physiological dose and after 3 hours and after 7 days during treatment with betamethasone in a supra physiological dose.
- Metabolite profile changes between physiological and supra physiological doses of betamethasone. [Changes in metabolome (units depending on the kind of metabolome) during 7 days of treatment with two different doses of betamethasone]
By using mas spectrometry, metabolite profile changes in blood, urine and saliva will be identified at four timepoints: after 3 hours and after 7 days during treatment with betamethasone in a physiological dose and after 3 hours and after 7 days during treatment with betamethasone in a supra physiological dose.
Secondary Outcome Measures
- Messenger RNA (mRNA)/miRNA profile changes between physiological and supra physiological doses of betamethasone. [Changes in mRNA/miRNA (Svedberg Unit, S) during 7 days of treatment with two different doses of betamethasone]
By using array based transcriptomics (both mRNA and miRNA), mRNA/miRNA profile changes in blood, urine and saliva will be identified at four timepoints: after 3 hours and after 7 days during treatment with betamethasone in a physiological dose and after 3 hours and after 7 days during treatment with betamethasone in a supra physiological dose.
- Changes in glucose metabolism between physiological and supra physiological doses of betamethasone. [Changes in glucose metabolism (units depending on sample analysis) during 7 days of treatment with two different doses of betamethasone]
Conventional markers for glucose metabolism in blood will be identified at four timepoints: after 3 hours and after 7 days during treatment with betamethasone in a physiological dose and after 3 hours and after 7 days during treatment with betamethasone in a supra physiological dose.
- Changes in lipid-profile between physiological and supra physiological doses of betamethasone. [Changes in lipid-profile (units depending on sample analysis) during 7 days of treatment with two different doses of betamethasone]
Conventional markers for lipid-profile in blood will be identified at four timepoints: after 3 hours and after 7 days during treatment with betamethasone in a physiological dose and after 3 hours and after 7 days during treatment with betamethasone in a supra physiological dose.
- Changes in bone-markers between physiological and supra physiological doses of betamethasone. [Changes in levels of bone-markers in blood (units depending on sample analysis) during 7 days of treatment with two different doses of betamethasone]
Bone-markers in blood will be identified at four timepoints: after 3 hours and after 7 days during treatment with betamethasone in a physiological dose and after 3 hours and after 7 days during treatment with betamethasone in a supra physiological dose.
- Changes in self-reported Quality of Life between physiological and supra physiological doses of betamethasone using the Addison-specific Quality of Life questionnaire (ADDIQoL). [Changes in units of the ADDIQoL questionnaire (units on a scale) after 7 days of treatment with two different doses of betamethasone]
Self-reported health-related quality of life and general well-being will be assessed using the ADDIQoL questionnaire after 7 days of treatment with a physiological dose of betamethasone and after 7 days of treatment with a supra physiological dose of betamethasone.
- Changes in self-reported Quality of Life between physiological and supra physiological doses of betamethasone using the Psychological General Well-being (PGWB) index. [Changes in units of the PGWB index (units on a scale) after 7 days of treatment with two different doses of dexamethasone]
Self-reported health-related quality of life and general well-being will be assessed using the PGWB index after 7 days of treatment with a physiological dose of betamethasone and after 7 days of treatment with a supra physiological dose of betamethasone.
- Changes in self-reported quality of life and fatigue between physiological and supra physiological doses of betamethasone using the Fatigue impact scale (FIS) [Changes in units in the FIS (units on a scale) after 7 days of treatment with two different doses of betamethasone]
Self-reported health-related quality of Life, general well-being and fatigue will be assessed using the FIS questionnaire after 7 days of treatment with a physiological dose of betamethasone and after 7 days of treatment with a supra physiological dose of betamethasone.
- Changes in self-reported quality of life and fatigue between physiological and supra physiological doses of betamethasone using the Functional Outcomes of Sleep Questionnaire (FOSQ). [Changes in units in the FOSQ (units on a scale) after 7 days of treatment with two different doses of betamethasone]
Self-reported health-related quality of life, general well-being and fatigue will be assessed using FOSQ after 7 days of treatment with a physiological dose of betamethasone and after 7 days of treatment with a supra physiological dose of betamethasone.
- Changes in daily physical activity between physiological and supra physiological doses of betamethasone [Changes in daily physical activity (units provided in connected software) after 7 days of treatment with two different doses of betamethasone]
Daily physical activity will be objectively evaluated using a wrist accelerometer during 7 days of treatment with a physiological dose of betamethasone and during 7 days of treatment with a supra physiological dose of betamethasone.
- Changes in sleep quality between physiological and supra physiological doses of betamethasone [Changes in sleep quality (measurements and units provided in connected software) after 7 days of treatment with two different doses of betamethasone]
Sleep quality will be objectively evaluated using a wrist worn sleep monitor during the last night of a 7 day treatment period with a physiological dose of betamethasone and the last night of a 7 day treatment period with a supra physiological dose of betamethasone.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Males and females at ages 20-65 years
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Previously diagnosed (e.g. more than 12 months ago) with primary adrenal insufficiency due to autoimmune adrenalitis, i.e. Addison´s disease
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A stable daily glucocorticoid replacement dose for at least 3 months prior to study entry
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An oral glucocorticoid replacement dose of 15-30 mg Hydrocortisone total daily dose
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If needed, a stable fludrocortisone replacement dose for at least 3 months prior to study entry
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Body mass index (BMI) of 20-35 kg/m2
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Ability to comply to the protocol procedures and having signed informed consent to participate in the study
Exclusion Criteria:
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Clinical or laboratory signs of significant cerebral, cardiovascular, respiratory, hepaticobiliary/ pancreatic disease which in the investigators judgement may interfere with the study assessment of completion of the study
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Clinically significant renal dysfunction with a serum creatinine above 150 mmol/L
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Pregnant or lactating women
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Diabetes Mellitus
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Systemic infections
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Regular dehydroepiandrosterone (DHEA) medication for the past 4 weeks
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Any medication with agents which in the investigators judgement might interfere with the study drugs kinetics, including therapies affecting gastro intestinal emptying or motility
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Alcohol/drug abuse or any other condition associated with poor patient compliance, including expected non-cooperation, as judged by the investigator
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Hypersensitivity to the active substance or any excipients used in the study drug of choice
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Any additional underlying disease that may need regular or periodic pharmacological treatment with glucocorticoids during the trail, such as asthma, skin- or eye conditions treated with inhaled or topical glucocorticoids
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Any additional underlying condition that needs treatment with intramuscular or intra-articular steroid injections during the trial
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Centrum for Endocrinology and Metabolism, Sahlgenska University Hospital | Gothenburg | Sweden | 413 45 |
Sponsors and Collaborators
- Göteborg University
Investigators
- Principal Investigator: Gudmundur Johannsson, Prof., MD, Vastra Gotaland Region, Sahlgrenska University Hospital, dept. of Endocrinology
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- DOSCORT
- 2016-004078-16