Hydrocortisone Replacement in Patients With Secondary Adrenal Insufficiency (SUPREME CORT)

University Medical Center Groningen (UMCG)

Status and phase: Completed; Phase 4

Conditions: Adrenal Insufficiency

Treatments: Drug: Hydrocortisone

Study type: Interventional

Funder types: Other

Identifiers

NCT01546922

NL 35668.042.11

2011-000864-82 (EudraCT Number)

Details and patient eligibility

About

The aim of this study is to investigate whether a physiologically low hydrocortisone (HC) dose is better for cognition as compared to a physiologically high HC dose. In addition, quality of life, metabolic profile and somatosensation will be described in relation to HC dose.

Full description

• Rationale: A wide variety in hydrocortisone (HC) substitution dose-regimens are considered physiological for patients with adrenal insufficiency. However, it is likely that cognition is negatively influenced by higher cortisol exposure to the brain. No studies have been performed to assess the effects of treatment regimens with a low physiological HC substitution dose on cognition in comparison to a high physiological HC substitution dose. These treatment regimens should take body weight and multiple dosing into account. In addition, substitution doses should be monitored by clinical evaluation and biochemical analysis for adverse effects associated with over- or under-replacement.
• Intervention: Patients with secondary adrenal insufficiency will be randomized in two groups to receive either a low dose HC (0.2-0.3 mg/kg body weight) for 10 weeks followed by 10 weeks of high dose HC (0.4-0.6 mg/kg body weight) or vice versa. At baseline and after both treatment periods, patients will be tested.

Enrollment: 63 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients with secondary adrenal insufficiency.
• Age ≥ 18 - 75 years
• ≥ One year after tumor treatment with surgery and/or radiotherapy
• On stable concomitant medications for at least six months prior to entry of study
• Body weight 50-100 kg

Exclusion criteria

• Inability of legal consent
• Documented cognitive impairment
• Drug abuse/dependence
• History of / current psychiatric disorders
• Use of anti-epileptics (e.g. carbamezapine)
• Cushing Disease
• Type 1 diabetes or Type 2 diabetes with medication known to induce hypoglycemia (f.e. Sulfonylurea derivatives
• Current treatment for second malignancy
• Have a significant medical condition (e.g. hepatic, respiratory, or cardiovascular) which, in the opinion of the investigator, may interfere with the interpretation of results and safety or efficacy evaluations.
• A history of frequent hypocortisolism
• Hospitalization during study
• Work in shifts

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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63 participants in 2 patient groups

First low dose HC followed by high dose HC

Active Comparator group

Description:

First low dose of hydrocortisone = 0.2-0.3 mg/kg body weight for 10 weeks followed by a high dose of hydrocortisone = 0.4-0.6 mg/kg body weight

Treatment:

Drug: Hydrocortisone

First high dose HC followed by low dose HC

Active Comparator group

Description:

First a high dose of hydrocortisone = 0.4-0.6 mg/kg body weight for 10 weeks followed by a low dose of hydrocortisone = 0.2-0.3 mg/kg body weight

Treatment:

Drug: Hydrocortisone