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A Study of Markers of Glucocorticoid Effects in Patients With Addisons Disease (DOSCORT)

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ClinicalTrials.gov Identifier: NCT03210545
Recruitment Status : Not yet recruiting
First Posted : July 7, 2017
Last Update Posted : November 2, 2018
Sponsor:
Information provided by (Responsible Party):
Göteborg University

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 dexamethasone 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
Addison Disease Drug: Dexamethasone Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: A Dose-response Study of Markers of Glucocorticoid Effects (DOSCORT): A Single-blinded, Randomized, 2-dose, Cross-over Study
Estimated Study Start Date : September 1, 2019
Estimated Primary Completion Date : December 1, 2020
Estimated Study Completion Date : December 1, 2020


Arm Intervention/treatment
Active Comparator: dexamethasone - physiological dose
Replacing participants hydrocortisone with a daily dose of dexamethasone in an estimated physiological dose during one treatment period.
Drug: Dexamethasone
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 dexamethasone 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: dexamethasone - supra physiological dose
Replacing participants hydrocortisone with a daily dose of dexamethasone in an estimated supra physiological dose during one treatment period.
Drug: Dexamethasone
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 dexamethasone 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 Measures :
  1. Protein profile changes between physiological and supra physiological doses of dexamethasone. [ Time Frame: Changes in proteome (g/dl or umol/l) during 7 days of treatment with two different doses of dexamethasone ]
    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 dexamethasone in a physiological dose and after 3 hours and after 7 days during treatment with dexamethasone in a supra physiological dose.

  2. Metabolite profile changes between physiological and supra physiological doses of dexamethasone. [ Time Frame: Changes in metabolome (units depending on the kind of metabolome) during 7 days of treatment with two different doses of dexamethasone ]
    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 dexamethasone in a physiological dose and after 3 hours and after 7 days during treatment with dexamethasone in a supra physiological dose.


Secondary Outcome Measures :
  1. Messenger RNA (mRNA)/miRNA profile changes between physiological and supra physiological doses of dexamethasone. [ Time Frame: Changes in mRNA/miRNA (Svedberg Unit, S) during 7 days of treatment with two different doses of dexamethasone ]
    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 dexamethasone in a physiological dose and after 3 hours and after 7 days during treatment with dexamethasone in a supra physiological dose.

  2. Changes in glucose metabolism between physiological and supra physiological doses of dexamethasone. [ Time Frame: Changes in glucose metabolism (units depending on sample analysis) during 7 days of treatment with two different doses of dexamethasone ]
    Conventional markers for glucose metabolism in blood will be identified at four timepoints: after 3 hours and after 7 days during treatment with dexamethasone in a physiological dose and after 3 hours and after 7 days during treatment with dexamethasone in a supra physiological dose.

  3. Changes in lipid-profile between physiological and supra physiological doses of dexamethasone. [ Time Frame: Changes in lipid-profile (units depending on sample analysis) during 7 days of treatment with two different doses of dexamethasone ]
    Conventional markers for lipid-profile in blood will be identified at four timepoints: after 3 hours and after 7 days during treatment with dexamethasone in a physiological dose and after 3 hours and after 7 days during treatment with dexamethasone in a supra physiological dose.

  4. Changes in bone-markers between physiological and supra physiological doses of dexamethasone. [ 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 dexamethasone ]
    Bone-markers in blood will be identified at four timepoints: after 3 hours and after 7 days during treatment with dexamethasone in a physiological dose and after 3 hours and after 7 days during treatment with dexamethasone in a supra physiological dose.

  5. Changes in self-reported Quality of Life between physiological and supra physiological doses of dexamethasone using the Addison-specific Quality of Life questionnaire (ADDIQoL). [ Time Frame: Changes in units of the ADDIQoL questionnaire (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 ADDIQoL questionnaire after 7 days of treatment with a physiological dose of dexamethasone and after 7 days of treatment with a supra physiological dose of dexamethasone.

  6. Changes in self-reported Quality of Life between physiological and supra physiological doses of dexamethasone using the Psychological General Well-being (PGWB) index. [ Time Frame: 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 dexamethasone and after 7 days of treatment with a supra physiological dose of dexamethasone.

  7. Changes in self-reported quality of life and fatigue between physiological and supra physiological doses of dexamethasone using the Fatigue impact scale (FIS) [ Time Frame: Changes in units in the FIS (units on a scale) after 7 days of treatment with two different doses of dexamethasone ]
    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 dexamethasone and after 7 days of treatment with a supra physiological dose of dexamethasone.

  8. Changes in self-reported quality of life and fatigue between physiological and supra physiological doses of dexamethasone using the Functional Outcomes of Sleep Questionnaire (FOSQ). [ Time Frame: Changes in units in the FOSQ (units on a scale) after 7 days of treatment with two different doses of dexamethasone ]
    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 dexamethasone and after 7 days of treatment with a supra physiological dose of dexamethasone.

  9. Changes in daily physical activity between physiological and supra physiological doses of dexamethasone [ Time Frame: Changes in daily physical activity (units provided in connected software) after 7 days of treatment with two different doses of dexamethasone ]
    Daily physical activity will be objectively evaluated using a wrist accelerometer during 7 days of treatment with a physiological dose of dexamethasone and during 7 days of treatment with a supra physiological dose of dexamethasone.

  10. Changes in sleep quality between physiological and supra physiological doses of dexamethasone [ Time Frame: Changes in sleep quality (measurements and units provided in connected software) after 7 days of treatment with two different doses of dexamethasone ]
    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 dexamethasone and the last night of a 7 day treatment period with a supra physiological dose of dexamethasone.



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Ages Eligible for Study:   20 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males and females at ages 20-60 years
  • Previously diagnosed (eg.. more than 12 months ago) with primary adrenal insufficiency due to autoimmune adrenalitis, i.e. Addison´s disease
  • 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
  • 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, hepatobiliary/ 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
  • Any additional underlying disease that may need regular or periodic pharmacological treatment with glucocorticoids
  • Any medication with agents which in the investigators judgement might interfere with the study drugs kinetics, including therapies affecting GI emptying or motility
  • Diabetes Mellitus diagnosis
  • Regular Dehydroepiandrosterone (DHEA) medication for the past 4 weeks
  • Pregnant or lactating women
  • 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
  • Systemic fungal infections

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03210545


Contacts
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Contact: Johanna Mc Queen, MD 0046313428588 johanna.mcqueen@gu.se
Contact: Gudmundur Johannsson, Prof., MD gudmundur.johannsson@gu.se

Locations
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Sweden
Centrum for Endocrinology and Metabolism, Sahlgenska University Hospital Not yet recruiting
Gothenburg, Sweden, 413 45
Contact: Johanna Mc Queen, MD       johanna.mcqueen@gu.se   
Sub-Investigator: Johanna Mc Queen, MD         
Sponsors and Collaborators
Göteborg University
Investigators
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Principal Investigator: Gudmundur Johannsson, Prof., MD Vastra Gotaland Region, Sahlgrenska University Hospital, dept. of Endocrinology

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Responsible Party: Göteborg University
ClinicalTrials.gov Identifier: NCT03210545     History of Changes
Other Study ID Numbers: DOSCORT
2016-004078-16 ( EudraCT Number )
First Posted: July 7, 2017    Key Record Dates
Last Update Posted: November 2, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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
Keywords provided by Göteborg University:
Biomarker
Glucocorticoids
Metabolism
Additional relevant MeSH terms:
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Addison Disease
Adrenal Insufficiency
Adrenal Gland Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Dexamethasone
Dexamethasone acetate
Hydrocortisone
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Hydrocortisone hemisuccinate
Glucocorticoids
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action