The Treatment of Adrenal Crisis With Inhaled Prednisolone

NCT05639127 | Unknown Early Phase 1 DMC

• 1 other identifier: NL81816.056.22
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Adrenal Insufficiency

Outcome Measures

Primary Outcomes (2)

• Tmax

  The time from nebulization to peak concentration prednisolone (Tmax (min))

  4 hours

• AUC

  The area under the curve (AUC (h\*nmol/L))

  4 hours

Secondary Outcomes (4)

• Cmax

  4 hours

• T1/2

  4 hours

• CL

  4 hours

• Vd

  4 hours

Study Arms (1)

Low dose, wash out, high dose

EXPERIMENTAL

Drug: Prednisolone

Interventions

Prednisolone DRUG

Nebulization of prednisolone

Low dose, wash out, high dose

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: 18 - 75 years
• Woman who use reliable contraceptives or with a negative pregnancy test
• Equal sex distribution

You may not qualify if:

• 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)

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (1)

UMCG

Groningen, 9713 GZ, Netherlands

RECRUITING

MeSH Terms

Conditions

Adrenal Insufficiency

Interventions

Prednisolone

Condition Hierarchy (Ancestors)

Adrenal Gland Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Central Study Contacts

Annet Vulto, MD

CONTACT

+31503617293; a.vulto@umcg.nl

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open label single group

Study Record Dates

• First Submitted: August 25, 2022
• First Posted: December 6, 2022
• Study Start: November 3, 2022
• Primary Completion: November 30, 2022
• Study Completion: March 1, 2023
• Last Updated: December 6, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: After completion study
• Access Criteria: Upon reasonable request

Locations

NL (1)