Back to resultsA Study of Markers of Glucocorticoid Effects in Patients With Addisons Disease (DOSCORT)
Primary Purpose
Addison Disease
Status
Unknown status
Phase
Phase 4
Locations
Sweden
Study Type
Interventional
Intervention
Betamethasone
Sponsored by
About this trial
This is an interventional treatment trial for Addison Disease focused on measuring Biomarker, Glucocorticoids, Metabolism
Eligibility Criteria
Inclusion Criteria:
- Males and females at ages 20-65 years
- Previously diagnosed (e.g. more than 12 months ago) with primary adrenal insufficiency due to autoimmune adrenalitis, i.e. Addison´s disease
- A stable daily glucocorticoid replacement dose for at least 3 months prior to study entry
- An oral glucocorticoid replacement dose of 15-30 mg Hydrocortisone total daily dose
- If needed, a stable fludrocortisone replacement dose for at least 3 months prior to study entry
- Body mass index (BMI) of 20-35 kg/m2
- Ability to comply to the protocol procedures and having signed informed consent to participate in the study
Exclusion Criteria:
- 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
- Clinically significant renal dysfunction with a serum creatinine above 150 mmol/L
- Pregnant or lactating women
- Diabetes Mellitus
- Systemic infections
- Regular dehydroepiandrosterone (DHEA) medication for the past 4 weeks
- Any medication with agents which in the investigators judgement might interfere with the study drugs kinetics, including therapies affecting gastro intestinal emptying or motility
- Alcohol/drug abuse or any other condition associated with poor patient compliance, including expected non-cooperation, as judged by the investigator
- Hypersensitivity to the active substance or any excipients used in the study drug of choice
- 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
- Any additional underlying condition that needs treatment with intramuscular or intra-articular steroid injections during the trial
Sites / Locations
- Centrum for Endocrinology and Metabolism, Sahlgenska University HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
betamethasone - physiological dose
betamethasone - supra physiological dose
Arm Description
Replacing participants hydrocortisone with a daily dose of betamethasone in an estimated physiological dose during one treatment period.
Replacing participants hydrocortisone with a daily dose of betamethasone in an estimated supra physiological dose during one treatment period.
Outcomes
Primary Outcome Measures
Protein profile changes between physiological and supra physiological 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.
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.
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.
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.
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.
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).
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.
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)
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).
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
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
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03210545
Brief Title
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
2. Study Status
Record Verification Date
April 2021
Overall Recruitment Status
Unknown status
Study Start Date
March 2, 2021 (Actual)
Primary Completion Date
November 30, 2021 (Anticipated)
Study Completion Date
December 31, 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Göteborg University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Addison Disease
Keywords
Biomarker, Glucocorticoids, Metabolism
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Masking Description
Double-blinded
Allocation
Randomized
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
betamethasone - physiological dose
Arm Type
Active Comparator
Arm Description
Replacing participants hydrocortisone with a daily dose of betamethasone in an estimated physiological dose during one treatment period.
Arm Title
betamethasone - supra physiological dose
Arm Type
Active Comparator
Arm Description
Replacing participants hydrocortisone with a daily dose of betamethasone in an estimated supra physiological dose during one treatment period.
Intervention Type
Drug
Intervention Name(s)
Betamethasone
Intervention Description
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.
Primary Outcome Measure Information:
Title
Protein profile changes between physiological and supra physiological doses of betamethasone.
Description
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.
Time Frame
Changes in proteome (g/dl or umol/l) during 7 days of treatment with two different doses of betamethasone
Title
Metabolite profile changes between physiological and supra physiological doses of betamethasone.
Description
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.
Time Frame
Changes in metabolome (units depending on the kind of metabolome) during 7 days of treatment with two different doses of betamethasone
Secondary Outcome Measure Information:
Title
Messenger RNA (mRNA)/miRNA profile changes between physiological and supra physiological doses of betamethasone.
Description
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.
Time Frame
Changes in mRNA/miRNA (Svedberg Unit, S) during 7 days of treatment with two different doses of betamethasone
Title
Changes in glucose metabolism between physiological and supra physiological doses of betamethasone.
Description
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.
Time Frame
Changes in glucose metabolism (units depending on sample analysis) during 7 days of treatment with two different doses of betamethasone
Title
Changes in lipid-profile between physiological and supra physiological doses of betamethasone.
Description
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.
Time Frame
Changes in lipid-profile (units depending on sample analysis) during 7 days of treatment with two different doses of betamethasone
Title
Changes in bone-markers between physiological and supra physiological doses of betamethasone.
Description
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.
Time Frame
Changes in levels of bone-markers in blood (units depending on sample analysis) during 7 days of treatment with two different doses of betamethasone
Title
Changes in self-reported Quality of Life between physiological and supra physiological doses of betamethasone using the Addison-specific Quality of Life questionnaire (ADDIQoL).
Description
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.
Time Frame
Changes in units of the ADDIQoL questionnaire (units on a scale) after 7 days of treatment with two different doses of betamethasone
Title
Changes in self-reported Quality of Life between physiological and supra physiological doses of betamethasone using the Psychological General Well-being (PGWB) index.
Description
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.
Time Frame
Changes in units of the PGWB index (units on a scale) after 7 days of treatment with two different doses of dexamethasone
Title
Changes in self-reported quality of life and fatigue between physiological and supra physiological doses of betamethasone using the Fatigue impact scale (FIS)
Description
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.
Time Frame
Changes in units in the FIS (units on a scale) after 7 days of treatment with two different doses of betamethasone
Title
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).
Description
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.
Time Frame
Changes in units in the FOSQ (units on a scale) after 7 days of treatment with two different doses of betamethasone
Title
Changes in daily physical activity between physiological and supra physiological doses of betamethasone
Description
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.
Time Frame
Changes in daily physical activity (units provided in connected software) after 7 days of treatment with two different doses of betamethasone
Title
Changes in sleep quality between physiological and supra physiological doses of betamethasone
Description
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.
Time Frame
Changes in sleep quality (measurements and units provided in connected software) after 7 days of treatment with two different doses of betamethasone
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Males and females at ages 20-65 years
Previously diagnosed (e.g. more than 12 months ago) with primary adrenal insufficiency due to autoimmune adrenalitis, i.e. Addison´s disease
A stable daily glucocorticoid replacement dose for at least 3 months prior to study entry
An oral glucocorticoid replacement dose of 15-30 mg Hydrocortisone total daily dose
If needed, a stable fludrocortisone replacement dose for at least 3 months prior to study entry
Body mass index (BMI) of 20-35 kg/m2
Ability to comply to the protocol procedures and having signed informed consent to participate in the study
Exclusion Criteria:
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
Clinically significant renal dysfunction with a serum creatinine above 150 mmol/L
Pregnant or lactating women
Diabetes Mellitus
Systemic infections
Regular dehydroepiandrosterone (DHEA) medication for the past 4 weeks
Any medication with agents which in the investigators judgement might interfere with the study drugs kinetics, including therapies affecting gastro intestinal emptying or motility
Alcohol/drug abuse or any other condition associated with poor patient compliance, including expected non-cooperation, as judged by the investigator
Hypersensitivity to the active substance or any excipients used in the study drug of choice
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
Any additional underlying condition that needs treatment with intramuscular or intra-articular steroid injections during the trial
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Johanna Mc Queen, MD
Phone
0046313428588
Email
johanna.mcqueen@gu.se
First Name & Middle Initial & Last Name or Official Title & Degree
Gudmundur Johannsson, Prof., MD
Email
gudmundur.johannsson@gu.se
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gudmundur Johannsson, Prof., MD
Organizational Affiliation
Vastra Gotaland Region, Sahlgrenska University Hospital, dept. of Endocrinology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centrum for Endocrinology and Metabolism, Sahlgenska University Hospital
City
Gothenburg
ZIP/Postal Code
413 45
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Johanna Mc Queen, MD
Email
johanna.mcqueen@gu.se
First Name & Middle Initial & Last Name & Degree
Johanna Mc Queen, MD
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
A Study of Markers of Glucocorticoid Effects in Patients With Addisons Disease (DOSCORT)
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