Continuous Subcutaneous Hydrocortisone Infusion In Addison's Disease and Type 1 Diabetes

NCT01840189 | Terminated Phase 2 DMC

• 2 other identifiers: 2012/22182012/005516-26
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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.

Conditions

Addison Disease; Type 1 Diabetes

Keywords

Addison disease; Type 1 diabetes; treatment

Outcome Measures

Primary Outcomes (1)

• nocturnal hypoglycemic events

  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

  4 months

Secondary Outcomes (3)

• o Nocturnal glycemic variability

  4 months

• hormone and metabolic profile

  4 months

• o Subjective health status

  4 months

Study Arms (2)

Cortef

ACTIVE COMPARATOR

Treatment A is oral hydrocortisone replacement( Cortef 5 mg)with weight-adjusted doses as suggested by Mah et al , will take 2 months

Other: Solu-cortef

Solu-cortef

ACTIVE COMPARATOR

This is the treatment B by continuous subcutaneous hydrocortisone infusion. Solu-cortef infusion will be given as Solu-Cortef Act-o-Vial 50mg/ml, , produced by Pfizer. Pump designed for subcutaneous insulin infusion can be used for subcutaneous administration.

Other: Cortef

Interventions

Cortef OTHER

Treatment A is oral hydrocortisone replacement ( Cortef 5 mg) administered according to weight-adjusted doses for 2 months

Solu-cortef

Solu-cortef OTHER

Treatment B is continuous subcutaneous hydrocortisone infusion with the initial standard dose of 10mg/m2/24hrs. Body surface area will be calculated according to the nomogram from the formula of Du Bois and Du Bois. This part of the study will take 2 months.

Cortef

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- primary Addison's disease in combination with long-standing Type 1 diabetes

You may not qualify if:

• cardiovascular disease
• active malignant disease
• pregnant women
• pharmacological treatment with glucocorticoids or drugs that interfere with cortisol metabolism (antiepileptics, rifampicin, St. Johns war, estrogens)

Sponsors & Collaborators

• Haukeland University Hospital: lead

Study Sites (1)

Haukeland University Hospiatl

Bergen, 5021, Norway

Location

Related Publications (9)

• Van den Driessche A, Eenkhoorn V, Van Gaal L, De Block C. Type 1 diabetes and autoimmune polyglandular syndrome: a clinical review. Neth J Med. 2009 Dec;67(11):376-87.

  PMID: 20009114 BACKGROUND

• Barker JM. Compounding risk for hypoglycemia: type 1 diabetes and Addison's disease. Diabetes Technol Ther. 2012 May;14(5):383-5. doi: 10.1089/dia.2012.0043. Epub 2012 Apr 16. No abstract available.

  PMID: 22506859 BACKGROUND

• Berger B, Stenstrom G, Sundkvist G. Incidence, prevalence, and mortality of diabetes in a large population. A report from the Skaraborg Diabetes Registry. Diabetes Care. 1999 May;22(5):773-8. doi: 10.2337/diacare.22.5.773.

  PMID: 10332680 BACKGROUND

• Bergthorsdottir R, Leonsson-Zachrisson M, Oden A, Johannsson G. Premature mortality in patients with Addison's disease: a population-based study. J Clin Endocrinol Metab. 2006 Dec;91(12):4849-53. doi: 10.1210/jc.2006-0076. Epub 2006 Sep 12.

  PMID: 16968806 BACKGROUND

• Elbelt U, Hahner S, Allolio B. Altered insulin requirement in patients with type 1 diabetes and primary adrenal insufficiency receiving standard glucocorticoid replacement therapy. Eur J Endocrinol. 2009 Jun;160(6):919-24. doi: 10.1530/EJE-08-1003. Epub 2009 Mar 9.

  PMID: 19273569 BACKGROUND

• Johannsson G, Nilsson AG, Bergthorsdottir R, Burman P, Dahlqvist P, Ekman B, Engstrom BE, Olsson T, Ragnarsson O, Ryberg M, Wahlberg J, Biller BM, Monson JP, Stewart PM, Lennernas H, Skrtic S. Improved cortisol exposure-time profile and outcome in patients with adrenal insufficiency: a prospective randomized trial of a novel hydrocortisone dual-release formulation. J Clin Endocrinol Metab. 2012 Feb;97(2):473-81. doi: 10.1210/jc.2011-1926. Epub 2011 Nov 23.

  PMID: 22112807 BACKGROUND

• Lovas K, Husebye ES. Continuous subcutaneous hydrocortisone infusion in Addison's disease. Eur J Endocrinol. 2007 Jul;157(1):109-12. doi: 10.1530/EJE-07-0052.

  PMID: 17609409 BACKGROUND

• Bryan SM, Honour JW, Hindmarsh PC. Management of altered hydrocortisone pharmacokinetics in a boy with congenital adrenal hyperplasia using a continuous subcutaneous hydrocortisone infusion. J Clin Endocrinol Metab. 2009 Sep;94(9):3477-80. doi: 10.1210/jc.2009-0630. Epub 2009 Jun 30.

  PMID: 19567522 BACKGROUND

• Mah PM, Jenkins RC, Rostami-Hodjegan A, Newell-Price J, Doane A, Ibbotson V, Tucker GT, Ross RJ. Weight-related dosing, timing and monitoring hydrocortisone replacement therapy in patients with adrenal insufficiency. Clin Endocrinol (Oxf). 2004 Sep;61(3):367-75. doi: 10.1111/j.1365-2265.2004.02106.x.

  PMID: 15355454 BACKGROUND

Related Links

• Endocrine Society

MeSH Terms

Conditions

Addison Disease; Diabetes Mellitus, Type 1

Interventions

Hydrocortisone; hydrocortisone hemisuccinate

Condition Hierarchy (Ancestors)

Adrenal Insufficiency; Adrenal Gland Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Study Officials

• Kristian Løvås, MD, PhD

  Haukeland University Hospital

  STUDY DIRECTOR

• Katerina Simunkova, PhD

  Haukeland University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2013
• First Posted: April 25, 2013
• Study Start: April 24, 2013
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: March 1, 2024

Record last verified: 2016-12

Locations

NO (1)