Treatment Study in Patients Treated With Both Insulin & Hydrocortisone (INSCORT)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Diabetes Mellitus; Adrenal Insufficiency; Polyglandular Autoimmune Syndrome
• Intervention / Treatment: Drug: OD dual-release Hydrocortisone; Drug: TID Hydrocortisone

• Study Type: Interventional
• Enrollment (Anticipated): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Gothenburg, Sweden
    • Sahlgrenska University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Vastra Gotaland Region
• Collaborators: Sahlgrenska University Hospital, Sweden; The Gothenburg Society of Medicine; Åke Wibergs Stiftelse; Pilloxa

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2023
• Primary Completion (Anticipated): December 1, 2024
• Study Completion (Anticipated): December 1, 2026

Study Registration Dates

• First Submitted: January 18, 2023
• First Submitted That Met QC Criteria: January 27, 2023
• First Posted (Actual): February 8, 2023

Study Record Updates

• Last Update Posted (Actual): April 18, 2023
• Last Update Submitted That Met QC Criteria: April 13, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Randomized Controlled Trial; Insulin treatment; Hydrocortisone treatment; Opposing effects on glucose metabolism
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Adrenal Gland Diseases; Adrenal Insufficiency; Polyendocrinopathies, Autoimmune; Anti-Inflammatory Agents; Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate; Hydrocortisone hemisuccinate
• Other Study ID Numbers: INS.CORT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No