Clinical Trial: Continuous Subcutaneous Hydrocortisone Infusion in Congenital Adrenal Hyperplasia

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Continuous Subcutaneous Hydrocortisone Infusion in Congenital Adrenal Hyperplasia

Brief Summary: The conventional glucocorticoid replacement therapy in congenital adrenal hyperplasia (CAH) renders the cortisol levels unphysiological, which may cause symptoms and long-term complications. Glucocorticoid replacement is technically feasible by continuous subcutaneous hydrocortisone infusion (CSHI), and can mimic the normal diurnal cortisol rhythm. This method was recently applied to treat a patient through a critical phase of puberty. This is a clinical trial aiming to evaluate CSHI treatment in patients with CAH. The main objective is to determine the effects of CSHI on metabolic parameters (androstenedione and 17-hydroxyprogesterone profiles, and testosterone,adrenocorticotropic hormone(ACTH), cortisol, and bone markers), and to determine the required glucocorticoid doses. Secondary objectives are to determine effects on clinical status, body weight, blood pressure and other metabolic parameters, as well as on subjective health status (AddiQoL, SF36).

Detailed Summary:

CAH patients are treated with glucocorticoids and mineralocorticoids. Ideally, the glucocorticoid doses should be sufficient to suppress the elevated ACTH secretion, and hence attenuate the increase in androgen levels. Because of this, CAH patients use higher steroid doses than patients with autoimmune adrenal insufficiency (Addison's disease) and therefore are in higher risk of developing glucocorticoid side effects. The natural glucocorticoids, hydrocortisone (cortisol) or cortisone acetate, are preferred during childhood because of the growth suppressive effects of the longer acting synthetic glucocorticoids, prednisolone and dexamethasone. There is no consensus as to which type of glucocorticoid and which doses should be used for adult CAH patients. Glucocorticoids display a typical diurnal variation, which the current therapy does not restore, leading to both to over- or undertreatment. Some CAH patients experience symptoms that may be due to unphysiological glucocorticoid replacement therapy.

For selected CAH patients with poor response to conventional replacement therapy, or with problematic side effects such as impaired growth, weight gain, metabolic syndrome, and osteoporosis, continuous subcutaneous hydrocortisone infusion (CSHI) might become a treatment option. CSHI treatment would also be facilitated by the use of the small disposable pumps now developed for insulin treatment.

CSHI: Pharmacodynamics, Pharmacokinetics, and safety Hydrocortisone is identical to cortisol; the pharmacodynamics does not depend on mode of delivery. A hydrocortisone solution can be safely applied for three days in the insulin pump without major day-to-day variation. A daily dose of 10 mg/m2 body surface area/day restores normal levels of saliva cortisol in most patients. Thus, it is possible to mimic the physiological diurnal cortisol
Sponsor: Haukeland University Hospital

Current Primary Outcome: Androgen levels [ Time Frame: 3 months ]

Androgen levels as parameters of adequate suppression of androgen production


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Steroid metabolism [ Time Frame: 4 months ]
    levels of ACTH
  • bone metabolism [ Time Frame: 3 months ]
  • fasting glucose [ Time Frame: 4 months ]
  • body mass index [ Time Frame: 3 months ]
  • Dual-energy X-ray absorptiometry (DXA) [ Time Frame: 6 months ]
    body composition, bone mineral density
  • Subjective health status [ Time Frame: 3 months ]
    questionnaire
  • waist circumference [ Time Frame: 3 month ]
    cm
  • hip circumference [ Time Frame: 3 months ]
    cm
  • blood pressure [ Time Frame: 3 months ]
  • fasting insulin [ Time Frame: 3-4 months ]
  • glycated haemoglobin (Hb1AC) [ Time Frame: 4 months ]
  • lipid levels [ Time Frame: 4 months ]
  • c-reactive protein [ Time Frame: 4 months ]
  • Steroid metabolism [ Time Frame: 4 months ]
    cortisol levels


Original Secondary Outcome: Same as current

Information By: Haukeland University Hospital

Dates:
Date Received: January 10, 2013
Date Started: February 2013
Date Completion: January 2017
Last Updated: December 20, 2016
Last Verified: December 2016