Clinical trial NCT03210545: A Study of Markers of Glucocorticoid Effects in Patients With Addisons Disease (DOSCORT)
Official title: A Dose-response Study of Markers of Glucocorticoid Effects (DOSCORT): A Double-blinded, Randomized, 2-dose, Cross-over Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Addison Disease
Keywords: Biomarker
Glucocorticoids
Metabolism
Lead sponsor: Göteborg University
Sponsor class: OTHER
First posted: 2017-07-07
Enrollment: 30
Sex: ALL
Minimum age (years): 20
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Males and females at ages 20-65 years
2. Previously diagnosed (e.g. more than 12 months ago) with primary adrenal insufficiency due to autoimmune adrenalitis, i.e. Addison´s disease
3. A stable daily glucocorticoid replacement dose for at least 3 months prior to study entry
4. An oral glucocorticoid replacement dose of 15-30 mg Hydrocortisone total daily dose
5. If needed, a stable fludrocortisone replacement dose for at least 3 months prior to study entry
6. Body mass index (BMI) of 20-35 kg/m2
7. Ability to comply to the protocol procedures and having signed informed consent to participate in the study

Exclusion Criteria:

1. 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
2. Clinically significant renal dysfunction with a serum creatinine above 150 mmol/L
3. Pregnant or lactating women
4. Diabetes Mellitus
5. Systemic infections
6. Regular dehydroepiandrosterone (DHEA) medication for the past 4 weeks
7. Any medication with agents which in the investigators judgement might interfere with the study drugs kinetics, including therapies affecting gastro intestinal emptying or motility
8. Alcohol/drug abuse or any other condition associated with poor patient compliance, including expected non-cooperation, as judged by the investigator
9. Hypersensitivity to the active substance or any excipients used in the study drug of choice
10. 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
11. Any additional underlying condition that needs treatment with intramuscular or intra-articular steroid injections during the trial

Primary outcomes:
measure: Protein profile changes between physiological and supra physiological doses of betamethasone.
timeFrame: Changes in proteome (g/dl or umol/l) during 7 days of treatment with two different doses of betamethasone
measure: Metabolite profile changes between physiological and supra physiological doses of betamethasone.
timeFrame: Changes in metabolome (units depending on the kind of metabolome) during 7 days of treatment with two different doses of betamethasone
Secondary outcomes:
measure: Messenger RNA (mRNA)/miRNA profile changes between physiological and supra physiological doses of betamethasone.
timeFrame: Changes in mRNA/miRNA (Svedberg Unit, S) during 7 days of treatment with two different doses of betamethasone
measure: Changes in glucose metabolism between physiological and supra physiological doses of betamethasone.
timeFrame: Changes in glucose metabolism (units depending on sample analysis) during 7 days of treatment with two different doses of betamethasone
measure: Changes in lipid-profile between physiological and supra physiological doses of betamethasone.
timeFrame: Changes in lipid-profile (units depending on sample analysis) during 7 days of treatment with two different doses of betamethasone
measure: Changes in bone-markers between physiological and supra physiological doses of betamethasone.
timeFrame: Changes in levels of bone-markers in blood (units depending on sample analysis) during 7 days of treatment with two different doses of betamethasone
measure: Changes in self-reported Quality of Life between physiological and supra physiological doses of betamethasone using the Addison-specific Quality of Life questionnaire (ADDIQoL).
timeFrame: Changes in units of the ADDIQoL questionnaire (units on a scale) after 7 days of treatment with two different doses of betamethasone
measure: Changes in self-reported Quality of Life between physiological and supra physiological doses of betamethasone using the Psychological General Well-being (PGWB) index.
timeFrame: Changes in units of the PGWB index (units on a scale) after 7 days of treatment with two different doses of dexamethasone
measure: Changes in self-reported quality of life and fatigue between physiological and supra physiological doses of betamethasone using the Fatigue impact scale (FIS)
timeFrame: Changes in units in the FIS (units on a scale) after 7 days of treatment with two different doses of betamethasone
measure: 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).
timeFrame: Changes in units in the FOSQ (units on a scale) after 7 days of treatment with two different doses of betamethasone
measure: Changes in daily physical activity between physiological and supra physiological doses of betamethasone
timeFrame: Changes in daily physical activity (units provided in connected software) after 7 days of treatment with two different doses of betamethasone
measure: Changes in sleep quality between physiological and supra physiological doses of betamethasone
timeFrame: Changes in sleep quality (measurements and units provided in connected software) after 7 days of treatment with two different doses of betamethasone
Other outcomes:
Locations:
city: Gothenburg
country: Sweden
facility: Centrum for Endocrinology and Metabolism, Sahlgenska University Hospital
Study officials:
affiliation: Vastra Gotaland Region, Sahlgrenska University Hospital, dept. of Endocrinology
name: Gudmundur Johannsson, Prof., MD
role: PRINCIPAL_INVESTIGATOR
References: