Modified-release Compared to Conventional Hydrocortisone on Diurnal Fatigue in Secondary Hypoadrenalism

NCT ID: NCT02282150

Last Updated: 2017-02-23

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-31
• Study Completion Date: 2017-12-31

Brief Summary

Despite optimized hydrocortisone replacement regimes, many patients with adrenal insufficiency (AI) suffer from impaired quality of life (QoL). Characteristically, patients report high fatigue levels at certain times during the day. A modified-release hydrocortisone has been shown to improve QoL, particularly fatigue, in patients with primary AI. However, it is unknown, if the same effect can be observed in patients with secondary AI. Further, no studies have evaluated the effect, taking into account the diurnal variation of fatigue. A novel survey method termed Ecological Momentary Assessments (EMA) has the potential to provide reliable measurements of diurnal variations in patient-reported outcomes, such as fatigue. We will compare the effect of modified-release compared to conventional hydrocortisone on fatigue in patients with secondary AI due to pituitary disease, and hereby assess the feasibility of EMA as outcome in future large-scale randomised clinical trials (RCTs).

Detailed Description

The study is conducted as an open-label, single-arm, two-period, crossover pilot trial. Includible patients are observed for 5 weeks on their usual treatment (twice or thrice daily hydrocortisone). Assessments of QoL, in terms of EMA assessments, to be used as baseline measurement in the study, are collected for 20 days preceded by a 5 days technology adaptation phase. Thereafter participants are shifted to modified release hydrocortisone (Plenadren) once daily (OD), on a dose as per Summary of Product Characteristics (SmPC). Assessments of QoL to be used as outcome of intervention in the study are performed after 12.5 weeks after initiation of Plenadren intervention treatment, in order to take into consideration the period of re-adjustment of the body after the switch from conventional hydrocortisone to Plenadren. As done at the baseline observation, EMA measurement is preceded by a five days technology adaptation phase. At the end of the intervention treatment period, the patients will be shifted to their usual hydrocortisone treatment and will be followed at the outpatient clinic according to the directives of the clinic. Biochemical parameters; blood samples, DEXA scan, 24 hour blood pressure and salivary cortisol, will be assessed at baseline and after 16 weeks, as part of the safety evaluation of Plenadren.

Conditions

Adrenal Insufficiency

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Conventional vs modified hydrocortisone;

5 weeks of conventional hydrocortisone followed by 16 weeks of modified-release hydrocortisone (Plenadren)

Group Type: OTHER

Hydrocortisone

Intervention Type: DRUG

Usual hydrocortisone dosage regimen; 10-40 mg hydrocortisone administered twice or thrice daily for 5 weeks

Plenadren

Intervention Type: DRUG

10-40 mg modified-release hydrocortisone in tablets, once a day for 16 weeks

Interventions

Hydrocortisone

Usual hydrocortisone dosage regimen; 10-40 mg hydrocortisone administered twice or thrice daily for 5 weeks

Intervention Type: DRUG

Plenadren

10-40 mg modified-release hydrocortisone in tablets, once a day for 16 weeks

Intervention Type: DRUG

Other Intervention Names

Modified-release hydrocortisone

Eligibility Criteria

Inclusion Criteria

• Diagnosed with adrenal insufficiency due to hypopituitarism
• In steady twice or thrice daily (10-40 mg) hydrocortisone replacement treatment
• Written informed consent
• For women: Use of reliable methods of contraception in clinical trials in accordance with the definition by the Danish Health and Medicines Authority; intrauterine devices or hormonal methods (oral contraceptives, contraceptive implants, transdermal patches, hormonal vaginal devices or injections with prolonged release).

Exclusion Criteria

• Pregnancy
• Breast feeding
• Acromegaly
• Cushing's Disease
• Diabetes Mellitus
• Other major confounding disease
• Known or expected hypersensitivity to any of the excipients
• Lack of compliance (attendance and medication)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ulla Feldt-Rasmussen

OTHER

Sponsor Role: lead

Responsible Party

Ulla Feldt-Rasmussen

Professor, MD, DMSc

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Ulla Feldt-Rasmussen, MD, DMSc

Role: PRINCIPAL_INVESTIGATOR

Rigshospitalet, Denmark

Other Identifiers

2014-002039-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

H-1-2014-073

Identifier Type: OTHER

Identifier Source: secondary_id

PLEN-EMA-hypo

Identifier Type: -

Identifier Source: org_study_id