Clinical Trial: Continuous Subcutaneous Hydrocortisone Infusion In Addison`s Disease and Type 1 Diabetes

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Continuous Subcutaneous Hydrocortisone Infusion In Addison`s Disease and Type 1 Diabetes

Brief Summary:

The conventional glucocorticoid replacement therapy in primary adrenal insufficiency (Addison's disease) renders the cortisol levels unphysiological, which may cause symptoms and long-term complications.

The majority of Addison's patients have other organ-specific autoimmune disease, which poses challenges to the replacement therapy. Of particular interest is the combination of Addison`s disease and type 1 diabetes, since cortisol affects glucose homeostasis. The clinical experience is that this subgroup of patients is difficult to treat, but very little research has been done to understand and improve their situation.

Glucocorticoid replacement is technically feasible by continuous subcutaneous hydrocortisone infusion, and can mimic the normal diurnal cortisol rhythm. This pilot study aims to further evaluate continuous subcutaneous hydrocortisone infusion treatment in terms of metabolic effects especially glycemic control in patients with the combination of Addison`s disease and type 1 diabetes in an 5 months cross-over design open clinical pilot study.


Detailed Summary:

Treatment of Addison`s disease includes glucocorticoid and mineralocorticoid replacement. Despite optimized therapy with these steroids, many patients suffer from impaired quality of life and increased mortality. The etiology of the premature death is complicated and may include a combination of inadequate treatment of adrenal crisis, patient non-compliance, and undetected hypoglycemia, in addition to being associated with increased cardiovascular, malignant, and infectious disease deaths. The relative risk of death for patients with Type 1 Diabetes is 3.8 in Sweden. Having Type 1 diabetes and Addison`s disease significantly increased the risk of death when compared with having adrenal insufficiency alone. The risk for premature death in patients with the combination of Type 1 diabetes and Addison`s disease has not been extensively studied and appears to contribute to a small portion of the increased mortality seen in patients with Addison`s disease.

Cortisol has particularly potent effects on blood glucose levels, otherwise Addison`s disease affects the production of cortisol, an important counterregulatory hormone for hypoglycaemia. Lack of cortisol might increase the risk of hypoglycemic episodes, whereas over-replacement might cause hyperglycemia. Because steroid replacement may cause significant insulin resistance, it is challenging to adjust insulin doses to maintain optimal glycemic control. Little is known about the effects of unphysiological glucocorticoid replacement therapy on glucose and lipid metabolism, but there has been concern about long-term metabolic consequence. Current glucocorticoid replacement results in large fluctuations in the cortisol levels directly influencing glucose homeostasis and, consequently, making accompanying insulin treatment difficult to manage. Different types, regimens and doses of glucocorticoids are now used in adrenal insuffici
Sponsor: Haukeland University Hospital

Current Primary Outcome: nocturnal hypoglycemic events [ Time Frame: 4 months ]

severe hypoglycemia (needs for another person's assistance, blood glucose ≤ 3.1 mmol ⁄ L or prompt recovery after oral carbohydrate, i.v glucose or glucagon administration) and insulin requirement


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • o Nocturnal glycemic variability [ Time Frame: 4 months ]
    monitored by continuous glucose monitor system
  • hormone and metabolic profile [ Time Frame: 4 months ]
    • Hormone levels : insulin like growth factor 1, growth hormone
    • Steroid metabolism: adrenocorticotropic hormone , cortisol
    • Metabolic profile: fructosamine, HBA1C, lipid levels, C reactive protein , homeostasis model assessment index
  • o Subjective health status [ Time Frame: 4 months ]
    Self administration of questionnaires


Original Secondary Outcome: Same as current

Information By: Haukeland University Hospital

Dates:
Date Received: April 23, 2013
Date Started: May 2013
Date Completion:
Last Updated: January 31, 2017
Last Verified: December 2016