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

Phase 4

• Conditions: Adrenal Insufficiency
• Interventions: Drug: Hydrocortisone; Drug: Plenadren

• Registration Number: NCT02282150
• Lead Sponsor: Ulla Feldt-Rasmussen

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.

Study Timeline

• Study First Submitted: 2014-10-26
• Study First Submitted QC: 2014-11-03
• Study First Posted: 2014-11-04
• Study Start: 2016-10
• Status Verified: 2017-02
• Last Update Submitted: 2017-02-21
• Last Update Posted: 2017-02-23
• Primary Completion: 2017-11
• Study Completion: 2017-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Conventional vs modified hydrocortisone;	Plenadren	5 weeks of conventional hydrocortisone followed by 16 weeks of modified-release hydrocortisone (Plenadren)
Conventional vs modified hydrocortisone;	Hydrocortisone	5 weeks of conventional hydrocortisone followed by 16 weeks of modified-release hydrocortisone (Plenadren)

Primary Outcome Measures

Name	Time	Method
Ecological Momentary Assessment (EMA) fatigue profiles	25 days during conventional hydrocortisone treatment and for 25 days during Plenadren (intervention) treatment	Differences and variability of standard treatment vs. modified release hydrocortisone EMA fatigue profiles

Secondary Outcome Measures

Name	Time	Method
Quality of Life questionnaires	At baseline and after 16 weeks of Plenadren (intervention) treatment	Fatigue Impact Scale (FIS), AD-specific quality-of-life questionnaire (AddiQol) and the Short Form Health Survey (SF-36)
Safety (Biochemical parameters, DEXA scan, 24 hour blood pressure and salivary cortisol)	At baseline and after 16 weeks of Plenadren (intervention) treatment	Biochemical parameters, DEXA scan, 24 hour blood pressure and salivary cortisol