The Treatment of Adrenal Crisis With Inhaled Prednisolone

• Status: Recruiting
• Trial end date: 2023-03-01
• Target enrollment: 0
• Participant gender: All

Summary

Rationale: An adrenal crisis is an acute life-threatening event which may occur in patients with adrenal insufficiency. The initial emergency treatment consists of an intramuscular injection with 100 mg hydrocortisone administered by the patient or a bystander. The injection should be administered immediately. Although it is considered life-saving, it is not very patient-friendly, because of the several steps required for reconstitution, the intramuscular injection, the frequent presence of needle phobia, and pain at the injection site. Inhalation of predniso(lo)ne could be a more patient-friendly alternative.

Objective: This study investigates the pharmacokinetics of nebulized prednisolone in two different dosages.

Study design: Single-center, open-label study Study population: Healthy participants aged 18-75 years. Intervention (if applicable): Healthy volunteers receive a lower dose of nebulized prednisolone (46.75 mg).After a wash-out period of at least one week, each volunteer receives a higher dose of nebulized prednisolone (93.5 mg).

Main study parameters/endpoints: To establish the time from nebulizing to maximum prednisolone concentration in serum and the area under the curve of prednisolone.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Participants are exposed to a single supraphysiological dose of glucocorticoids on two separate occasions. The risk of SAE is very limited. There is a small risk of an AE during blood sampling. If it is demonstrated that therapeutic plasma concentrations of prednisolone can be reached by nebulizing prednisolone, we intend to use the pharmacokinetic data to design and perform a clinical study with a dry-powder micronized prednisone inhalation. This would represent a novel and promising alternative treatment for an adrenal crisis. Patients with adrenal insufficiency could then be offered a much more patient-friendly and reliable alternative for intramuscular hydrocortisone injection.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University Medical Center Groningen
• Treatments: Prednisolone

Criteria

Inclusion Criteria:

• Age: 18 - 75 years

• Woman who use reliable contraceptives or with a negative pregnancy test

• Equal sex distribution

Exclusion Criteria:

• Heart failure

• Known liver or kidney disease

• Dependency on glucocorticoids

• Adrenogenital syndrome

• Infectious disease

• Uncontrolled hypertension defined as a blood pressure > 180/110 mmHg

• Pregnancy or breastfeeding

• Use of medication that interferes with cytochrome P450 (e.g. carbamazepine)