Clinical trial NCT02282150: Modified-release Compared to Conventional Hydrocortisone on Diurnal Fatigue in Secondary Hypoadrenalism
Official title: Effect of Modified-release Compared to Conventional Hydrocortisone on Fatigue, Measured by Ecological Momentary Assessments; a Pilot Study.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Adrenal Insufficiency
Keywords: Fatigue
Quality of Life
Hydrocortisone
Ecological Momentary Assessments
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2014-11-04
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Cross over
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Ecological Momentary Assessment (EMA) fatigue profiles
timeFrame: 25 days during conventional hydrocortisone treatment and for 25 days during Plenadren (intervention) treatment
Secondary outcomes:
measure: Quality of Life questionnaires
timeFrame: At baseline and after 16 weeks of Plenadren (intervention) treatment
measure: Safety (Biochemical parameters, DEXA scan, 24 hour blood pressure and salivary cortisol)
timeFrame: At baseline and after 16 weeks of Plenadren (intervention) treatment
Other outcomes:
Locations:
Study officials:
affiliation: Rigshospitalet, Denmark
name: Ulla Feldt-Rasmussen, MD, DMSc
role: PRINCIPAL_INVESTIGATOR
References: