Treatment Study in Patients Treated With Both Insulin & Hydrocortisone

Study Overview
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Brief Summary
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The aim of INS.CORT trial is, by studying glycemic variability in a well-defined patient group with both insulin & hydrocortisone (patients with concomitant insulin-treated diabetes & Addison's disease) and collecting information about the administration -time point and doses- of insulin, hydrocortisone and food intake with the help of new technology to improve the treatment in all patients treated with both insulin & glucocorticoids.

Official Title
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Randomized Cross-over Trial in Patients Treated With Both Insulin & Hydrocortisone

Conditions
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Diabetes Mellitus, Adrenal Insufficiency, Polyglandular Autoimmune Syndrome

Intervention / Treatment
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* Drug: OD dual-release Hydrocortisone
* Drug: TID Hydrocortisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women at age 18 to 70 years, with BMI 18-32 kg/m2 and well-defined both insulin-treated diabetes & Addison's disease for >12 months each, on insulin treatment and stable hydrocortisone replacement with once-daily dual-release hydrocortisone (20-30 mg/day) for >3 months. Exclusion Criteria: Any medication with other glucose lowering agents than insulin Any additional underlying or intercurrent disease that may need regular or periodic pharmacological treatment with glucocorticoids during the study period, including infectious diseases Any medication with agents which in the investigator's judgement might interfere with the study drugs kinetics, including therapies affecting gastrointestinal emptying or motility Any medication with oral estrogen supplementation and/or regular DHEA medication for the past 4 weeks Clinically significant renal dysfunction with a serum creatinine above 160 mmol/L Active malignancy Clinical or laboratory signs of significant cerebral, cardiovascular, respiratory, hepatobiliary/pancreatic disease which in the investigator's judgement may interfere with the study assessment 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Single-center, randomized, open-label, two-period cross-over trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Once-daily dual-release hydrocortisone<br> | Drug: OD dual-release Hydrocortisone<br>* Treatment with once-daily dual-release hydrocortisone<br>* Other names: Once-daily dual-release hydrocortisone;|
| Active Comparator: Thrice-daily conventional immediate-release hydrocortisone<br> | Drug: TID Hydrocortisone<br>* Treatment with thrice-daily conventional immediate-release hydrocortisone<br>* Other names: Thrice-daily conventional immediate-release hydrocortisone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| glycemic variability | glycemic variability | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HbA1c | HbA1c | 4 weeks | 
| Time in range (glucose) | Time in range (glucose) | 4 weeks | 
| Time above range (glucose) | Time above range (glucose) | 4 weeks | 
| Time below range (glucose) | Time below range (glucose) | 4 weeks | 
| Cortisol exposure-time profile | Cortisol exposure-time profile | 4 weeks | 
| systolic blood pressure | systolic blood pressure in sitting position | 4 weeks | 
| diastolic blood pressure | diastolic blood pressure in sitting position | 4 weeks | 
| ADDIQoL | questionnaire: the Addison-specific quality-of-life (ADDIQoL) The AddiQoL is a 36-item questionnaire; each item contains six scoring categories. Twenty-five items are negative Health-Related Quality of Life (HRQoL) statements that need to be reversed for questionnaire scoring; thus, a higher score indicates a higher level of HRQoL. | 4 weeks | 
| PGWB | questionnaire: the Psychological General Well-Being (PGWB) index The Psychological General Well-Being Index (PGWBI) is a measure of the level of subjective psychological well-being. In detail, it assesses self-representations of intrapersonal affective or emotional states reflecting a sense of subjective well-being or distress and thus captures what we could call a subjective perception of well-being. Consisting of 22 standardized items (6 items for the short form), the tool produces a single measure of psychological well-being. The full measure also provides sub-scales to assess the following domains: anxiety, depression, positive well-being, self-control, general health, and vitality. | 4 weeks | 
| FIS | questionnaire: the Fatigue Impact Scale (FIS) The FIS was developed to assess the symptom of fatigue as part of an underlying chronic disease or condition. Consisting of 40 items, the instrument evaluates the effect of fatigue on three domains of daily life: cognitive functioning, physical functioning, and psychosocial functioning minimum and maximum values, and whether higher scores mean a better or worse outcome. Higher scores mean a worse outcome. Min 0 points, max 160 points. | 4 weeks | 
| FOSQ | questionnaire: the Functional Outcomes of Sleep Questionnaire (FOSQ) Disease specific quality of life questionnaire to determine functional status in adults; measures are designed to assess the impact of disorders of excessive sleepiness on multiple activities of everyday living and the extent to which these abilities are improved by effective treatment. Name of categories assessed: Activity level, vigilance, intimacy and sexual relationships, general productivity, social outcome, rate the difficulty of performing a given activity on a 4-point scale (no difficulty to extreme difficulty). Higher scores mean a better outcome. Min 0 points, max 120 points. | 4 weeks | 
| Fever | Incidence of infections with high fever (patients judgement) | 4 weeks | 
| CD16 | immunophenotyping of peripheral blood mononuclear cells (PBMCs) with measurement of soluble CD16 | 4 weeks | 
| ADAM17 | immunophenotyping of peripheral blood mononuclear cells (PBMCs) with measurement of soluble ADAM17 | 4 weeks | 
| transcriptomics | RNA sequencing for large-scale study of gene expression in circulation | 4 weeks | 
| microRNAs | large-scale study of microRNAs in circulation | 4 weeks | 
| proteomics | large-scale study of proteomes (proteins produced in study subjects) | 4 weeks | 
| metabolomics | large-scale study of metabolome (metabolites produced in study subjects) | 4 weeks | 
| hsCRP fibrinogen, immunoglobulin | High-sensitivity C-reactive Protein (laboratory measurement) | 4 weeks | 
| SR | erythrocyte sedimentation rate (laboratory measurement) | 4 weeks | 
| fibrinogen | fibrinogen (laboratory measurement) | 4 weeks | 
| immunoglobulins | immunoglobulin levels in fem klasser: IgA, IgD, IgE, IgG och IgM | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Insulin treatment, Hydrocortisone treatment, Opposing effects on glucose metabolism, Randomized Controlled Trial