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

NCT03210545 | Completed Phase 4

• 2 other identifiers: DOSCORT2016-004078-16
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Addison Disease

Keywords

Biomarker; Glucocorticoids; Metabolism

Outcome Measures

Primary Outcomes (2)

• 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.

  Changes in proteome (g/dl or umol/l) during 7 days of treatment with two different doses of betamethasone

• 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.

  Changes in metabolome (units depending on the kind of metabolome) during 7 days of treatment with two different doses of betamethasone

Secondary Outcomes (10)

• 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

• 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

• 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

• 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

• 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

Study Arms (2)

betamethasone - physiological dose

ACTIVE COMPARATOR

Replacing participants hydrocortisone with a daily dose of betamethasone in an estimated physiological dose during one treatment period.

Drug: Betamethasone

betamethasone - supra physiological dose

ACTIVE COMPARATOR

Replacing participants hydrocortisone with a daily dose of betamethasone in an estimated supra physiological dose during one treatment period.

Drug: Betamethasone

Interventions

Betamethasone DRUG

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.

betamethasone - physiological dose; betamethasone - supra physiological dose

Eligibility Criteria

• Age: 20 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Göteborg University: lead

Study Sites (1)

Centrum for Endocrinology and Metabolism, Sahlgenska University Hospital

Gothenburg, 413 45, Sweden

Location

MeSH Terms

Conditions

Addison Disease

Interventions

Betamethasone

Condition Hierarchy (Ancestors)

Adrenal Insufficiency; Adrenal Gland Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Gudmundur Johannsson, Prof., MD

  Vastra Gotaland Region, Sahlgrenska University Hospital, dept. of Endocrinology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double-blinded
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2017
• First Posted: July 7, 2017
• Study Start: March 2, 2021
• Primary Completion: November 9, 2021
• Study Completion: February 16, 2022
• Last Updated: April 24, 2025

Record last verified: 2025-04

Locations

SE (1)